FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE: EMERGENCY USE AUTHORIZATION OF MODERNA COVID-19 VACCINE (2023-2024 FORMULA), FOR INDIVIDUALS 6 MONTHS THROUGH 11 YEARS OF AGE

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FULL FACT SHEET FOR HEALTHCARE PROVIDERS

1 EMERGENCY USE AUTHORIZATION

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of Moderna COVID-19 Vaccine (2023-2024 Formula) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months through 11 years of age.

Justification for Emergency Use of Vaccines During the COVID-19 Pandemic

There is currently an outbreak of COVID-19 caused by SARS-CoV-2. The Secretary of the Department of Health and Human Services (HHS) has:

An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that the use of EUA authority is justified, based on a determination that there is a public health emergency, or a significant potential for a public health emergency, that affects or has a significant potential to affect, national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:

Information Regarding Available Alternative Vaccines for the Prevention of COVID-19 in Individuals 6 Months Through 11 Years of Age

There may be clinical trials or availability under EUA of other COVID-19 vaccines, including vaccines that contain or encode the spike protein of the Omicron variant XBB.1.5 of SARS-CoV-2.

For information on clinical studies of Moderna COVID-19 Vaccine and other vaccines for the prevention of COVID-19, see www.clinicaltrials.gov.

• •Determined that there is a public health emergency, or a significant potential for a public health emergency related to COVID-19.See U.S. Department of Health and Human Services, Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020; https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency. See also U.S. Department of Health and Human Services, Amended Determination of a Public Health Emergency or Significant Potential for a Public Health Emergency Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b). March 15, 2023 (“Amended Determination”); https://www.federalregister.gov/documents/2023/03/20/2023-05609/covid-19-emergency-use-authorization-declaration.
• •Declared that circumstances exist justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic.See U.S. Department of Health and Human Services, Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3, 85 FR 18250 (April 1, 2020); https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration. See also Amended Determination (“The declarations issued pursuant to section 564(b)(1) of the FD&C Act that circumstances exist justifying the authorization of emergency use of certain in vitro diagnostics, personal respiratory protective devices, other medical devices and drugs and biological products, as set forth in those declarations, and that are based on the February 4, 2020 determination, remain in effect until those declarations are terminated in accordance with section 564 of the FD&C Act.”).

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

2.1 Preparation for Administration

• •Moderna COVID-19 Vaccine single dose vials contain a frozen suspension that does not contain a preservative and must be thawed prior to administration.
• •Thaw each vial before use following the instructions below.

2.2 Administration

Administer the 0.25 mL dose of Moderna COVID-19 Vaccine intramuscularly.

2.3 Dose and Schedule

Individuals 6 Months Through 4 Years of Age by Moderna COVID-19 Vaccination Status

a Previous dose(s) of Moderna COVID-19 vaccine(s) refers to Moderna COVID-19 Vaccine (Original monovalent) and Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5). These vaccines are no longer authorized for use in the United States.b For individuals with certain kinds of immunocompromise previously vaccinated with a Moderna COVID-19 vaccine, see text following the tables for dosing information.c Not previously vaccinated with any COVID-19 vaccine.d Individuals turning from 4 years to 5 years of age during the vaccination series should receive both doses with Moderna COVID-19 Vaccine (2023-2024 Formula).

Individuals 5 Years Through 11 Years of Age Irrespective of COVID-19 Vaccination Status

a For individuals with certain kinds of immunocompromise, see text following tables for dosing information.b COVID-19 vaccine refers to the monovalent COVID-19 vaccines (original) and the bivalent COVID-19 vaccines (Original and Omicron BA.4/BA.5). These vaccines are no longer authorized for use in the United States.

Individuals 6 Months through 11 Years of Age with Certain Kinds of Immunocompromise

Individuals 6 months through 11 years of age with certain kinds of immunocompromise Certain kinds of immunocompromise refers to individuals who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise. should complete at least a three-dose series with a COVID-19 vaccine, each dose one month apart. COVID-19 vaccine, each dose of the three-doses series given one month apart, refers to Moderna COVID-19 vaccines. Individuals turning from 11 to 12 years of age during the vaccination series may complete the series with doses of Moderna COVID-19 Vaccine (2023-2024 Formula). At least 1 dose should be with a COVID-19 vaccine (2023-2024 Formula).

An additional dose of Moderna COVID-19 Vaccine (2023-2024 Formula) may be administered at least 2 months following the last dose of a COVID-19 vaccine (2023-2024 Formula). For immunocompromised individuals 6 months through 4 years of age, the last dose of a COVID-19 vaccine (2023-2024 Formula) refers to a dose with Moderna COVID-19 Vaccine (2023-2024 Formula)., For immunocompromised individuals 5 years through 11 years of age, the last dose of a COVID-19 vaccine (2023-2024 Formula) refers to a dose with Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula) or Moderna COVID-19 Vaccine (2023-2024 Formula). Additional doses of Moderna COVID-19 Vaccine (2023-2024 Formula) may be administered at the discretion of the healthcare provider, taking into consideration the individual’s clinical circumstances. The timing of the additional doses may be based on the individual’s clinical circumstances.

• •If previously not vaccinated, complete the three-dose series with Moderna COVID-19 Vaccine (2023-2024 Formula).
• •If previously vaccinated with one or two dose(s) of Moderna COVID-19 Vaccine (Original monovalent) and/or the Moderna COVID-19 Vaccine, Bivalent, complete the remaining dose(s) in the three-dose series with Moderna COVID-19 Vaccine (2023-2024 Formula).
• •If previously vaccinated with three or more doses, administer a single dose of Moderna COVID-19 Vaccine (2023-2024 Formula) at least two months following the last previous dose. For immunocompromised individuals 6 months through 4 years of age, the last previous dose refers to the last dose of Moderna COVID-19 Vaccine (Original monovalent) or Moderna COVID-19 Vaccine, Bivalent which are no longer authorized for use in the U.S., For immunocompromised individuals 5 years through 11 years of age, the last previous dose refers to the last dose of a COVID-19 vaccine (Original monovalent) or bivalent COVID-19 vaccine which are no longer authorized for use in the U.S.

3 DOSAGE FORMS AND STRENGTHS

Moderna COVID-19 Vaccine is a suspension for injection.

A single dose is 0.25 mL.

4 CONTRAINDICATIONS

Do not administer Moderna COVID-19 Vaccine to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of Moderna COVID-19 Vaccine [see Description (11)] or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Moderna COVID-19 vaccine.

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Moderna COVID-19 Vaccine.

Monitor Moderna COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention (CDC) guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).

5.2 Myocarditis and Pericarditis

Postmarketing data with authorized or approved mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following vaccination. For Moderna COVID-19 Vaccine, the observed risk is highest in males 18 years through 24 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae.

The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to Moderna COVID-19 Vaccine.

5.5 Limitations of Vaccine Effectiveness

Moderna COVID-19 Vaccine may not protect all vaccine recipients.

6 ADVERSE REACTIONS

In clinical studies contributing to the safety assessment of Moderna COVID-19 Vaccine (2023-2024 Formula), participants received a 2-dose series one month apart (referred to as primary series) and subsequent doses referred to as booster doses, as described in Table 1 below.

Table 1: Clinical Studies

The safety data accrued with the Moderna COVID-19 Vaccine (Original monovalent, no longer authorized for use in the U.S.), Moderna’s bivalent COVID-19 vaccine (Original and Omicron BA.1) [not authorized or approved in the U.S., hereafter referred to as bivalent vaccine (Original and Omicron BA.1)] and Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (no longer authorized for use in the U.S.) are relevant to Moderna COVID-19 Vaccine (2023-2024 Formula) because these vaccines are manufactured using the same process.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

Moderna COVID-19 Vaccine (Original Monovalent) Administered as a Two-Dose Primary Series

Participants 18 Years of Age and Older

The safety of Moderna COVID-19 Vaccine was evaluated in an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase of the trial was conducted in the United States involving 30,346 participants 18 years of age and older who received at least one dose of Moderna COVID-19 Vaccine (100 mcg mRNA; n=15,184) or placebo (n=15,162) (Study 1, NCT04470427). Upon issuance of the Emergency Use Authorization (December 18, 2020) for Moderna COVID-19 Vaccine, participants were unblinded in a phased manner over a period of months to offer placebo participants Moderna COVID-19 Vaccine. The median duration of follow-up for safety after the second injection during the blinded phase was 4 months. The median duration of follow up for safety after the second injection including both the blinded phase and the open-label phase was 6 months.

In Study 1, the median age of the population was 52 years (range 18-95); 75.2% of participants were 18 years through 64 years of age and 24.8% were 65 years of age and older. Overall, 52.6% of the participants were male, 47.4% were female, 20.5% were Hispanic or Latino, 79.2% were White, 10.2% were African American, 4.6% were Asian, 0.8% were American Indian or Alaska Native, 0.2% were Native Hawaiian or Pacific Islander, 2.0% were other races, and 2.1% were Multiracial. Demographic characteristics were similar between participants who received Moderna COVID-19 Vaccine and those who received placebo.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for 28 days following each dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration (2 years). Among the 30,346 participants who had received at least 1 dose of vaccine (N=15,184) or placebo (N=15,162), unsolicited adverse events that occurred within 28 days following any vaccination were reported by 31.3% of participants (n=4,752) who received Moderna COVID-19 Vaccine and 28.6% of participants (n=4,338) who received placebo.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 1.7% of vaccine recipients and 0.8% of placebo recipients. These events included lymphadenopathy, lymphadenitis, lymph node pain, vaccination-site lymphadenopathy, injection-site lymphadenopathy, and axillary mass. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness at the injected arm.

During the 7-day follow-up period of any vaccination, hypersensitivity events of injection site rash or injection site urticaria, likely related to vaccination, were reported by 6 participants in the Moderna COVID-19 Vaccine group and none in the placebo group. Delayed injection site reactions that began >7 days after vaccination were reported in 1.4% of vaccine recipients and 0.7% of placebo recipients. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

In the blinded portion of the study, there were 8 reports of facial paralysis (including Bell’s palsy) in the Moderna COVID-19 Vaccine group, and 3 in the placebo group. In the 28-day follow-up period there were two cases of facial paralysis in the Moderna COVID-19 Vaccine group, which occurred on 8 and 22 days, respectively, after vaccination, and one in the placebo group, which occurred 17 days after vaccination. Currently available information on facial paralysis is insufficient to determine a causal relationship with the vaccine.

In the blinded portion of the study, there were 50 reports of herpes zoster in the Moderna COVID-19 Vaccine group, and 23 in the placebo group. In the 28-day period after any vaccination, there were 22 cases of herpes zoster in the Moderna COVID-19 Vaccine group, and 15 in the placebo group. Currently available information on herpes zoster infection is insufficient to determine a causal relationship with the vaccine.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Serious Adverse Events

During the blinded phase of the study, serious adverse events were reported by 1.8% (n=268) of participants who received Moderna COVID-19 Vaccine and 1.9% (n=292) of participants who received placebo.

There were three serious adverse events of angioedema/facial swelling in the vaccine group in recipients with a history of injection of dermatological fillers. The onset of swelling was reported 1-2 days after the second dose and was likely related to vaccination.

There were no other notable patterns or imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Participants 12 Years Through 17 Years of Age

The safety of Moderna COVID-19 Vaccine was evaluated in an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind clinical trial was conducted in the United States involving 3,726 participants 12 years through 17 years of age who received at least one dose of Moderna COVID-19 Vaccine (100 mcg mRNA; n=2,486) or placebo (n=1,240) (Study 3, NCT04649151). Participants started to enter an open-label, observational phase after May 10, 2021. After October 1, 2021, cases of potential myocarditis and/or pericarditis that were identified by the investigator or Applicant were adjudicated by an independent Cardiac Event Adjudication Committee (CEAC) to determine if they met the CDC definition of confirmed or probable myocarditis and/or pericarditis. A safety analysis was conducted in participants who received Moderna COVID-19 Vaccine (n=2,486) with a cut-off date of January 31, 2022. In these analyses, the median duration of follow-up including both the blinded and open-label phases was 312 days after Dose 2 and 95.7% of study participants had at least 6 months of follow-up after Dose 2.

Overall, 51.4% were male, 48.6% were female, 11.6% were Hispanic or Latino, 83.8% were White, 3.4% were African American, 6.0% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 1.0% were other races, and 4.5% were Multiracial. Demographic characteristics were similar among participants who received Moderna COVID-19 Vaccine and those who received placebo.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for 28 days following each dose. Serious adverse events and medically attended adverse events were recorded for the entire study duration. Among the 3,726 participants who had received at least 1 dose of vaccine (n=2,486) or placebo (n=1,240), unsolicited adverse events that occurred within 28 days following any vaccination were reported by 23.4% of participants (n=582) who received Moderna COVID-19 Vaccine and 19.1% of participants (n=237) who received placebo.

In the open-label portion of the study, a 14-year-old male experienced probable myocarditis with onset of symptoms 1 day after Dose 2 of Moderna COVID-19 Vaccine. Symptoms resolved after 8 days and no sequelae were observed at 5 months. This event was considered related to Moderna COVID-19 Vaccine and was subsequently adjudicated by the CEAC as probable myocarditis. There were no cases of myocarditis among placebo recipients.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 6.0% of vaccine recipients and 0.6% of placebo recipients. These events included lymphadenopathy, vaccination-site lymphadenopathy, and injection-site lymphadenopathy which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness in the injected arm.

During the 28-day follow-up period following any dose, hypersensitivity events of injection site rash or injection site urticaria, likely related to vaccination, were reported by 0.3% of participants in the Moderna COVID-19 Vaccine group and <0.1% in the placebo group. Delayed injection site reactions that began >7 days after vaccination were reported in 1.5% of vaccine recipients and in <0.1% of placebo recipients. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Serious Adverse Events

During the blinded portion of the study, serious adverse events were reported by 0.4% (n=9) of participants who received Moderna COVID-19 Vaccine and 0.2% (n=3) of participants who received placebo. In the open-label phase, an additional 12 Moderna COVID-19 Vaccine recipients reported serious adverse events. There were no serious adverse events considered causally related to the vaccine.

There were no notable patterns or imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Participants 6 Years Through 11 Years of Age

Study 4 (NCT04796896) is a Phase 2/3 clinical trial with multiple parts. The study included a randomized, placebo-controlled, observer-blind clinical trial component conducted in the United States and Canada. Safety data for Moderna COVID-19 Vaccine from the blinded portion of Study 3 included data in 4,002 participants 6 years through 11 years of age who received at least one dose of Moderna COVID-19 Vaccine (50 mcg mRNA; n=3,007) or placebo (n=995). As of the data cutoff date of November 10, 2021, the median duration of blinded follow-up for safety was 51 days after Dose 2, and 1,284 participants had been followed for at least 2 months after Dose 2 (vaccine=1,006, placebo=218).

Demographic characteristics in Study 4 were similar among participants who received Moderna COVID-19 Vaccine and those who received placebo. Overall, 50.8% were male, 49.2% were female, 18.5% were Hispanic or Latino, 65.6% were White, 10.0% were African American, 9.9% were Asian, 0.4% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 2.1% were other races, and 10.6% were Multiracial.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine (n=3,006) and participants receiving placebo (n=994) with at least 1 documented dose. Events that persisted for more than 7 days were followed until resolution.

The reported number and percentage of the solicited local and systemic adverse reactions in participants 6 years through 11 years of age by dose in Study 4 are presented in Table 2.

Table 2: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After Each Dose in Participants 6 Years Through 11 Years (Solicited Safety Set, Dose 1 and Dose 2)†

Solicited local and systemic adverse reactions reported following administration of Moderna COVID-19 Vaccine had a median duration of 2 to 3 days.

An assessment of reactogenicity among participants with evidence of prior SARS-CoV-2 infection (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]) compared to those with no evidence of infection at baseline (negative RT-PCR test and negative Elecsys immunoassay result at Day 1) was conducted. In ages 6 years through 11 years, 8.6% of participants (vaccine=257, placebo=87) had evidence of prior SARS-CoV-2 infection at baseline. Table 3 presents the number and percentage of the solicited local and systemic adverse reactions in Moderna COVID-19 Vaccine participants starting within 7 days after each dose by SARS-CoV-2 status.

Table 3: Number and Percentage of Participants 6 Years Through 11 Years Who Received Vaccine With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After Each Dose by SARS-CoV-2 Status (Solicited Safety Set, Dose 1 and Dose 2)†

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following each dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of November 10, 2021, among participants who had received at least 1 dose of vaccine or placebo (vaccine=3,007, placebo=995), unsolicited adverse events that occurred within 28 days following each vaccination were reported by 29.6% of participants (n=891) who received Moderna COVID-19 Vaccine and 25.1% of participants (n=250) who received placebo. In these analyses, 98.6% of study participants had at least 28 days of follow-up after Dose 2.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 1.8% of vaccine recipients and 0.6% of placebo recipients. These events included lymphadenopathy, lymph node pain, injection-site lymphadenopathy, and vaccination-site lymphadenopathy which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness in the injected arm.

During the 28-day follow-up period following any dose, hypersensitivity adverse events were reported in 4.3% of vaccine recipients and 2.1% of placebo recipients. Hypersensitivity events in the vaccine group included injection site rash and injection site urticaria, which are likely related to vaccination. Delayed injection site reactions that began >7 days after vaccination were reported in 2.7% of vaccine recipients and in 0.2% of placebo recipients. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

During the 28-day follow-up period following any dose, events of abdominal pain (including abdominal pain, abdominal pain upper, and abdominal pain lower) were reported by 1.1% of vaccine recipients and 0.6% of placebo recipients. Currently available information is insufficient to determine a causal relationship with the vaccine.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Serious Adverse Events

As of November 10, 2021, serious adverse events were reported by 0.2% (n=6) of participants who received Moderna COVID-19 Vaccine and 0.2% (n=2) participants who received placebo. None of the events in the Moderna COVID-19 Vaccine group were considered related to vaccine. In these analyses, 98.6% of study participants had at least 28 days of follow-up after Dose 2, and the median follow-up time for all participants was 51 days after Dose 2.

There were no notable patterns or imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Additional Safety Analyses

Participants 6 years through 11 years in Study 4 started to enter an open-label, observational phase after November 1, 2021. A long-term safety analysis was conducted in participants 6 years through 11 years from Study 4 who received Moderna COVID-19 Vaccine (n=3,007) with a cut-off date of February 21, 2022. In these analyses, the median duration of follow-up including both the blinded and open-label phases was 158 days after Dose 2. Through the cut-off date, there were no serious adverse events causally related to the vaccine.

Participants 6 Months Through 5 Years of Age

Study 4 (NCT04796896) is a Phase 2/3 clinical trial with multiple parts. The study included a randomized, placebo-controlled, observer-blind clinical trial component conducted in the United States and Canada. Safety data for Moderna COVID-19 Vaccine from the blinded portion of Study 4 included data in 6,388 participants 6 months through 5 years of age who received at least one dose of Moderna COVID-19 Vaccine (25 mcg mRNA; n=4,792) or placebo (n=1,596). As of the data cutoff date of February 21, 2022, the median duration of blinded follow-up for safety for participants 6 months through 23 months was 68 days after Dose 2. For participants 2 years through 5 years, the median duration of blinded follow-up for safety was 71 days after Dose 2.

For participants 6 months through 23 months, 51.1% were male, 48.9% were female, 13.2% were Hispanic or Latino, 79.0% were White, 3.1% were African American, 4.9% were Asian, 0.2% were American Indian or Alaska Native, 0.0% were Native Hawaiian or Pacific Islander, 1.5% were other races, and 10.6% were Multiracial. For participants 2 years through 5 years, 50.8% were male, 49.2% were female, 14.2% were Hispanic or Latino, 76.5% were White, 4.5% were African American, 6.0% were Asian, 0.4% were American Indian or Alaska Native, 0.3% were Native Hawaiian or Pacific Islander, 1.5% were other races, and 10.4% were Multiracial. Demographic characteristics were similar among participants who received Moderna COVID-19 Vaccine and those who received placebo.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine and participants receiving placebo with at least 1 documented dose (for participants 6 through 23 months, vaccine=1,758, placebo=585; for participants 24 months to 36 months, vaccine=986, placebo=338; for participants 37 months to 5 years, vaccine=2,030, placebo=659). Events that persisted for more than 7 days were followed until resolution.

The reported number and percentage of the solicited local and systemic adverse reactions by dose in Study 4 participants 6 months through 23 months of age are presented in Table 4, participants 24 months through 36 months of age are presented in Table 5, and participants 37 months to 5 years are presented in Table 6.

Table 4: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After Each Dose in Participants 6 Months Through 23 Months (Solicited Safety Set, Dose 1 and Dose 2)†

Table 5: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After Each Dose in Participants 24 Months Through 36 Months (Solicited Safety Set, Dose 1 and Dose 2)†

Table 6: Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After Each Dose in Participants 37 Months Through 5 Years (Solicited Safety Set, Dose 1 and Dose 2)†

Solicited local and systemic adverse reactions reported following administration of Moderna COVID-19 Vaccine had a median duration of 2 to 3 days for participants 6 months through 23 months of age and 2 days for participants 2 years through 5 years of age.

Solicited Adverse Reactions Among Participants with Evidence of Prior SARS-CoV-2 Infection

An assessment of reactogenicity among participants with evidence of prior SARS-CoV-2 infection (immunologic or virologic evidence of prior SARS-CoV-2 infection [defined as positive RT-PCR test and/or positive Elecsys immunoassay result at Day 1]) compared to those with no evidence of infection at baseline (negative RT-PCR test and negative Elecsys immunoassay result at Day 1) was conducted. In the 6 months through 23 months of age cohort, 6.1% of participants (vaccine=106, placebo=38) had evidence of prior SARS-CoV-2 infection at baseline. In the 2 years through 5 years of age cohort, 8.6% of participants (vaccine=266, placebo=82) had evidence of prior SARS-CoV-2 infection at baseline. In each age cohort, fever (temperature >38°C) was reported in a greater proportion of baseline SARS-CoV-2 positive vaccine participants compared to baseline SARS-CoV-2 negative vaccine participants. There were no notable differences in other reactogenicity events.

Safety of a 25-mcg dose in children 6 months through 4 years of age previously vaccinated with 2 or more doses of a Moderna COVID-19 vaccine is supported by these data on solicited adverse reactions in participants with evidence of prior SARS-CoV-2 infection, since the second dose represents a third exposure to the SARS-CoV-2 Spike antigen.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following each dose and follow-up is ongoing. Serious adverse events and medically attended adverse events will be recorded for the entire study duration.

As of February 21, 2022, among participants 6 months through 23 months of age who had received at least 1 dose of vaccine or placebo (vaccine=1,761, placebo=589), unsolicited adverse events that occurred within 28 days following each vaccination were reported by 49.3% of participants (n=869) who received Moderna COVID-19 Vaccine and 48.2% of participants (n=284) who received placebo. In these analyses, 83.1% of study participants 6 months through 23 months of age had at least 28 days of follow-up after Dose 2. Among participants 2 years through 5 years of age who had received at least 1 dose of vaccine or placebo (vaccine=3,031, placebo=1,007), unsolicited adverse events that occurred within 28 days following each vaccination were reported by 40.0% of participants (n=1,212) who received Moderna COVID-19 Vaccine and 37.5% of participants (n=378) who received placebo. In these analyses, 89.3% of study participants 2 years through 5 years of age had at least 28 days of follow-up after Dose 2.

During the 28-day follow-up period following any dose, lymphadenopathy-related events were reported by 1.5% of vaccine recipients and 0.2% of placebo recipients who were 6 months through 23 months of age and 0.9% of vaccine recipients and <0.1% of placebo recipients who were 2 years through 5 years of age. These events included lymphadenopathy, injection-site lymphadenopathy, and vaccination-site lymphadenopathy which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary (or groin) swelling/tenderness in the injected limb.

During the 28-day follow-up period following any dose, hypersensitivity adverse events were reported in 3.9% of vaccine recipients and 5.3% of placebo recipients who were 6 months through 23 months of age and 3.5% of vaccine recipients and 2.5% of placebo recipients who were 2 years through 5 years of age. Hypersensitivity events in the vaccine group included injection site rash and injection site urticaria, which are likely related to vaccination. Delayed injection site reactions that began >7 days after vaccination were reported in 1.2% of vaccine recipients and no placebo recipients who were 6 months through 23 months of age and 1.4% of vaccine recipients and <0.1% of placebo recipients who were 2 years through 5 years of age. Delayed injection site reactions included pain, erythema, and swelling and are likely related to vaccination.

During the 28-day follow-up period following any dose, events of abdominal pain (including abdominal pain, abdominal pain upper, and abdominal discomfort) were reported by 0.7% of vaccine recipients and 0.4% of placebo recipients who were 2 years through 5 years of age. Currently available information is insufficient to determine a causal relationship with the vaccine.

There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events that would suggest a causal relationship to Moderna COVID-19 Vaccine.

Serious Adverse Events

As of February 21, 2022, serious adverse events were reported by 0.9% (n=15) of participants who received vaccine and 0.2% (n=1) of participants who received placebo who were 6 months through 23 months of age and 0.3% (n=9) of participants who received Moderna COVID-19 Vaccine and 0.2% (n=2) of participants who received placebo who were 2 years through 5 years of age. In these analyses, 83.1% of study participants 6 months through 23 months of age had at least 28 days of follow-up after Dose 2, and the median follow-up time for all participants was 68 days after Dose 2. In these analyses, 89.3% of study participants 2 years through 5 years of age had at least 28 days of follow-up after Dose 2, and the median follow-up time for all participants was 71 days after Dose 2.

In participants 6 months through 23 months of age who received the vaccine, a 1-year-old female experienced serious adverse events of a Grade 3 fever 6 hours after Dose 1 and a febrile convulsion 1 day after Dose 1. These events were considered related to vaccination. In participants 2 years through 5 years of age who received Moderna COVID-19 Vaccine, none of the events were considered related to vaccine.

Moderna COVID-19 Vaccine (Original Monovalent) Administered as a First Booster Dose Following a Primary Series of Moderna COVID-19 Vaccine (Original Monovalent)

Participants 18 Years of Age and Older

Study 2 was a Phase 2, randomized, observer-blind, placebo-controlled, dose-confirmation study to evaluate the safety, reactogenicity, and immunogenicity of Moderna COVID-19 Vaccine in participants 18 years of age and older (NCT04405076). In this study, 198 participants received two doses 1 month apart of Moderna COVID-19 Vaccine primary series (100 mcg mRNA per dose). In an open-label-phase of the study, 171 of those participants received a single booster dose (50 mcg mRNA) at least 6 months (range of 5.8 to 8.5 months) after receiving the second dose of the primary series.

Among the 171 booster dose recipients, the median age was 55 years (range 18-87); 77.8% of participants were 18 years through 64 years of age, 22.2% were 65 years of age and older, 39.2% were male, 60.8% were female, 5.8% were Hispanic or Latino, 95.9% were White, 2.9% were African American, 0.6% were Asian, and 0.6% were American Indian or Alaska Native.

Unsolicited Adverse Events

Overall, the 171 participants who received a booster dose had a median follow-up time of 176 days after the booster dose to the database lock date (November 23, 2021). Through 28 days after the booster dose, unsolicited adverse events were reported by 14.6% of participants (n=25) after the booster dose. There were no unsolicited adverse events not already captured by solicited local and systemic reactions that were considered causally related to Moderna COVID-19 Vaccine.

Serious Adverse Events

There were no serious adverse events reported from the booster dose through 28 days after the booster dose. Through the database lock date (November 23, 2021), there were no serious adverse events following the booster dose considered causally related to Moderna COVID-19 Vaccine.

Participants 12 Years Through 17 Years of Age

Safety data for a booster dose of Moderna COVID-19 Vaccine in adolescents were collected in an ongoing Phase 3 clinical trial with multiple parts. The open-label booster portion of the study included 1,405 participants who were 12 years through 17 years of age at the time of first dose of the primary series and who received a booster dose of Moderna COVID-19 Vaccine (50 mcg mRNA) at least 5 months (range 2.1 to 16.9 months) after the second dose of the primary series (Study 3, NCT04649151). Overall, 51.5% were male, 48.5% were female, 13.4% were Hispanic or Latino, 84.9% were White, 3.1% were African American, 4.9% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 0.7% were other races, and 5.2% were Multiracial. The median duration of follow-up for safety after the booster dose was 204 days.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events were recorded for the entire study duration. As of August 15, 2022, among the 1,405 participants who had received a booster dose of Moderna COVID-19 Vaccine, unsolicited adverse events that occurred within 28 days following vaccination were reported by 14.9% of participants (n=209). In these analyses, 85.7% of study participants had at least 6 months of follow-up after the booster dose. Overall, there were no notable differences in the safety profiles observed between participants who had received a booster dose of Moderna COVID-19 Vaccine and those who had received a primary series.

Serious Adverse Events

Through the cut-off date of August 15, 2022, with a median follow-up duration of 204 days after the booster dose, there were no serious adverse events considered causally related to the vaccine.

Participants 6 Years Through 11 Years of Age

Safety data for a booster dose of Moderna COVID-19 Vaccine in individuals 6 years through 11 years of age were collected in an ongoing Phase 2/3 clinical trial with multiple parts. The open-label booster portion of the study involved 1,294 participants 6 years through 11 years of age who received a booster dose of Moderna COVID-19 Vaccine (25 mcg mRNA) at least 6 months after the second dose of the primary series (Study 4, NCT04796896). Overall, 51.9% were male, 48.1% were female, 15.6% were Hispanic or Latino, 65.7% were White, 11.0% were African American, 7.8% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 1.9% were other races, and 11.8% were Multiracial. As of the data cutoff date of May 23, 2022, the median duration of follow-up for safety was 29 days after the booster dose.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following the injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine. Events that persisted for more than 7 days were followed until resolution.

Table 7 presents the frequency and severity of reported solicited local and systemic adverse reactions among Study 4 Moderna COVID-19 Vaccine booster dose recipients 6 years through 11 years of age within 7 days of a booster vaccination.

Table 7: Number and Percentage of Participants 6 Years Through 11 Years of Age With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After the Moderna COVID-19 Vaccine Booster Dose (Solicited Safety Set)†

In participants who received a booster dose, the median duration of solicited local and systemic adverse reactions was 3 days.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of May 23, 2022, among the 1,294 participants who had received a booster dose, unsolicited adverse events that occurred within 28 days following vaccination were reported by 13.1% of participants (n=169). In these analyses, 55.4% of study participants had at least 28 days of follow-up after the booster dose. Serum sickness-like reaction with onset 10 days following administration of a booster dose was reported in an 8-year-old participant. This event was assessed as related to vaccination. After initiation of treatment with antihistamines and steroids, symptoms resolved within 15 days with the exception of intermittent urticaria that was ongoing 31 days after the onset of the reaction.

Serious Adverse Events

As of May 23, 2022, with a median follow-up duration of 29 days after the booster dose, there was one serious adverse event of abdominal pain reported 16 days following the booster dose by a 7-year-old participant. Currently available information is insufficient to determine a causal relationship with the vaccine.

Participants 17 Months Through 5 Years of Age

Safety data in support of a booster dose of Moderna COVID-19 Vaccine in individuals 6 months through 5 years of age were collected in participants 17 months through 5 years of age at the time of the booster dose in an ongoing Phase 2/3 clinical trial with multiple parts. The open-label booster portion of the study involved 145 participants 17 months through 5 years of age who received a booster dose of Moderna COVID-19 Vaccine (10 mcg mRNA) at least 6 months (range 8-13 months; median 10 months) after the completion of the Moderna COVID-19 Vaccine two-dose primary series (Study 4, NCT04796896). Overall, 55.2% were male, 44.8% were female, 10.3% were Hispanic or Latino, 80.0% were White, 2.8% were African American, 6.2% were Asian, 0.7% were American Indian or Alaska Native, 0.0% were Native Hawaiian or Pacific Islander, 2.8% were other races, and 7.6% were Multiracial. As of the data cutoff date of August 18, 2022, the median duration of follow-up for safety after the booster dose was 99 days.

Solicited Adverse Reactions

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following the injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine (10 mcg mRNA). Events that persisted for more than 7 days were followed until resolution.

The frequency and severity of reported solicited local and systemic adverse reactions within 7 days of a booster vaccination among participants 17 months through 36 months are presented in Table 8, and among participants 37 months through 5 years are presented in Table 9.

Table 8: Number and Percentage of Participants 17 Months Through 36 Months of Age With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After the Moderna COVID-19 Vaccine Booster Dose (Solicited Safety Set)†

Table 9: Number and Percentage of Participants 37 Months Through 5 Years With Solicited Local and Systemic Adverse Reactions Starting Within 7 Days* After the Moderna COVID-19 Vaccine Booster Dose (Solicited Safety Set)†

In participants who received a booster dose, the median duration of solicited local and systemic adverse reactions was 3 days.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of August 18, 2022, among the 145 participants who had received a booster dose, unsolicited adverse events that occurred within 28 days following vaccination were reported by 24.1% of participants (n=35). In these analyses, 99.3% of study participants had at least 28 days of follow-up. Through the cut-off date, there were no unsolicited adverse events not already captured as solicited local and systemic reactions that were considered causally related to Moderna COVID-19 Vaccine.

Serious Adverse Events

As of August 18, 2022, with a median follow-up duration after the booster dose of 99 days, there were no serious adverse events reported following the booster dose.

Moderna COVID-19 Vaccine Administered as a First Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine

The safety of a Moderna COVID-19 Vaccine booster dose in individuals who completed primary vaccination with another authorized or approved COVID-19 vaccine (heterologous booster dose) is inferred from the safety of a Moderna COVID-19 Vaccine booster dose administered following completion of a Moderna COVID-19 Vaccine primary series (homologous booster dose) and from data from an independent Phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States that evaluated a booster dose of Moderna COVID-19 Vaccine. The booster dose that study participants received contained twice the amount of mRNA compared to the authorized booster dose of Moderna COVID-19 Vaccine. In this study, adults who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks (range 12 to 20 weeks) prior to enrollment and who reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of one of three vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine. Adverse events were assessed through 28 days after the booster dose. An overall review of adverse reactions reported following the Moderna COVID-19 Vaccine heterologous booster dose did not identify any new safety concerns, as compared with adverse reactions reported following Moderna COVID-19 Vaccine primary series doses or homologous booster dose.

Moderna COVID-19 Vaccine Administered as a Second Booster Dose Following Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine

In an independently conducted study (Gili Regev‑Yochay, Tal Gonen, Mayan Gilboa, et al. 2022 DOI: 10.1056/NEJMc2202542), Moderna COVID-19 Vaccine was administered as a second booster dose to 120 participants 18 years of age and older who had received a 2-dose primary series and a first booster dose of Pfizer-BioNTech COVID-19 Vaccine at least 4 months prior. No new safety concerns were reported during up to three weeks of follow-up after the second booster dose.

Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose in Participants 18 Years of Age and Older

Study 5 (NCT04927065), a Phase 2/3 open-label study conducted in the United States, evaluated the immunogenicity, safety, and reactogenicity of a booster dose of the bivalent vaccine (Original and Omicron BA.1) compared to a booster dose of Moderna COVID-19 Vaccine (50 mcg mRNA; previously but no longer authorized for booster vaccination in individuals 18 years of age and older) when administered as a second booster dose to participants 18 years of age and older who had previously received a primary series and a first booster dose with Moderna COVID-19 Vaccine at least 3 months prior. The bivalent vaccine (Original and Omicron BA.1) contained 25 mcg of mRNA encoding the pre-fusion stabilized S-glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 25 mcg of mRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineage BA.1, for a total of 50 mcg mRNA per dose. The safety analysis set included 437 participants in the bivalent vaccine (Original and Omicron BA.1) booster dose group and 377 participants in the Moderna COVID-19 Vaccine booster dose group.

The median age of the population was 60 years (range 20-96); 490 (60.2%) participants were 18 years through 64 years of age and 324 (39.8%) were 65 years and older. Overall, 44.8% were male, 55.2% were female, 10.2% were Hispanic or Latino, 86.4% were White, 7.4% were African American, 3.7% were Asian, 0.1% were American Indian or Alaska Native, 0.1% were Native Hawaiian or Pacific Islander, 0.6% were other races, and 1.1% were Multiracial. Demographic characteristics were similar among participants who received the bivalent vaccine (Original and Omicron BA.1) and those who received Moderna COVID-19 Vaccine. Following the booster dose through the cutoff date of April 27, 2022, the median follow-up time was 43 days among bivalent vaccine (Original and Omicron BA.1) recipients and 57 days among Moderna COVID-19 Vaccine recipients.

Unsolicited Adverse Events

Participants were monitored for unsolicited adverse events for up to 28 days following the booster dose. Serious adverse events and medically attended adverse events will be recorded for the entire study duration. As of April 27, 2022, among participants who had received a booster dose (bivalent vaccine [Original and Omicron BA.1]=437, Moderna COVID-19 Vaccine=377), unsolicited adverse events that occurred within 28 days following vaccination were reported by 18.5% of participants (n=81) who received bivalent vaccine (Original and Omicron BA.1) and 20.7% of participants (n=78) who received Moderna COVID-19 Vaccine. In these analyses, 99.9% of study participants had at least 28 days of follow-up after the booster dose. The incidence of unsolicited adverse events was similar between the vaccine groups and no new safety concerns were identified.

Serious Adverse Events

As of April 27, 2022, the median duration of follow-up was 43 days among bivalent vaccine (Original and Omicron BA.1) recipients and 57 days among Moderna COVID-19 Vaccine recipients. Serious adverse events were reported by 0.7% (n=3) of participants who received bivalent vaccine (Original and Omicron BA.1) and 0.3% (n=1) of participants who received Moderna COVID-19 Vaccine. None of the events in the bivalent vaccine (Original and Omicron BA.1) group or Moderna COVID-19 Vaccine group were considered related to vaccine.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of SPIKEVAX, Moderna COVID-19 Vaccine and Moderna COVID-19 Vaccine, Bivalent. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.Cardiac Disorders: myocarditis, pericarditis Immune System Disorders: anaphylaxis, urticariaNervous System Disorders: syncope

6.3 Required Reporting for Adverse Events and Vaccine Administration Errors

Vaccination providers must report the listed events following administration of the Moderna COVID-19 Vaccine (2023-2024 Formula) to the Vaccine Adverse Event Reporting System (VAERS):

*Serious Adverse Events are defined as:

Instructions for Reporting to VAERS

Vaccination providers should complete and submit a VAERS form to FDA using one of the following methods:

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

The following steps are highlighted to provide the necessary information for safety tracking:

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to ModernaTX, Inc. using the contact information below or by providing a copy of the VAERS form to ModernaTX, Inc.

• •Vaccine administration errors whether or not associated with an adverse event
• •Serious adverse events* (irrespective of attribution to vaccination)
• •Cases of myocarditis
• •Cases of pericarditis
• •Cases of Multisystem Inflammatory Syndrome (MIS)
• •Cases of COVID-19 that results in hospitalization or death

7 DRUG INTERACTIONS

There are no data to assess the concomitant administration of Moderna COVID-19 Vaccine with other vaccines.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Moderna COVID-19 Vaccine during pregnancy. Individuals who are vaccinated with Moderna COVID-19 Vaccine during pregnancy are encouraged to enroll in the registry by calling 1-866-MODERNA (1-866-663-3762).

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on SPIKEVAX, Moderna COVID-19 Vaccine, Bivalent or Moderna COVID-19 Vaccine administered to pregnant individuals are insufficient to inform vaccine-associated risks in pregnancy.

In a developmental toxicity study, 0.2 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (100 mcg) and other ingredients included in a single primary series dose of Moderna COVID-19 Vaccine for individuals 12 years of age and older was administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior to mating, and on gestation days 1 and 13. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.

8.2 Lactation

Risk Summary

It is not known whether Moderna COVID-19 Vaccine is excreted in human milk. Data are not available to assess the effects of Moderna COVID-19 Vaccine on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Moderna COVID-19 Vaccine and any potential adverse effects on the breastfed child from Moderna COVID-19 Vaccine or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Moderna COVID-19 Vaccine is authorized for use in individuals 6 months through 11 years of age.

Moderna COVID-19 Vaccine is not authorized for use in individuals younger than 6 months of age or individuals 12 years of age and older.

8.6 Use in Immunocompromised Individuals

Safety and effectiveness of the Moderna COVID-19 Vaccine in individuals 6 months through 11 years of age with immunocompromise have been extrapolated from adult data. In an independent study (Hall VG, Ferreira VH, Ku T et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med 2021 DOI: 10.1056/NEJMc2111462; NCT04885907), safety and effectiveness of a third primary series dose of Moderna COVID-19 Vaccine have been evaluated in participants who received solid organ transplants. In this study, in 60 adult participants who had undergone various solid organ transplant procedures (heart, kidney, kidney-pancreas, liver, lung, pancreas) a median of 3.57 years previously (range 1.99-6.75 years) who received a third vaccine dose, the adverse event profile was similar to that after the second dose and no Grade 3 or Grade 4 events were reported. The administration of a third primary series vaccine dose appears to be only moderately effective in increasing antibody titers. Patients should be counseled to maintain physical precautions to help prevent COVID-19. In addition, close contacts of immunocompromised persons should be vaccinated, as appropriate for their health status.

11 DESCRIPTION

Moderna COVID-19 Vaccine is provided as a sterile white to off-white suspension for intramuscular injection.

Each 0.25 mL dose of Moderna COVID-19 Vaccine (2023-2024 Formula) contains 25 mcg nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of the SARS-CoV-2 Omicron variant lineage XBB.1.5. Each dose also contains the following ingredients: a total lipid content of 0.5 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.13 mg tromethamine, 0.62 mg tromethamine hydrochloride, 0.011 mg acetic acid, 0.049 mg sodium acetate trihydrate, and 21.8 mg sucrose.

Moderna COVID-19 Vaccine (2023-2024 Formula) does not contain a preservative.

The vial stoppers are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

The nucleoside-modified mRNA in Moderna COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

14 CLINICAL STUDIES

The effectiveness of Moderna COVID-19 Vaccine (2023-2024 Formula) for individuals 6 months through 11 years of age is based on:

• •effectiveness of Moderna COVID-19 Vaccine (Original monovalent) in individuals 6 months of age and older, and
• •immunogenicity of the bivalent vaccine (Original and Omicron BA.1) in individuals 18 years of age and older

14.1 Efficacy of Two-Dose Primary Series of Moderna COVID-19 Vaccine (Original Monovalent) in Participants 18 Years of Age and Older

Study 1 is an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase evaluated the efficacy, safety, and immunogenicity of Moderna COVID-19 Vaccine in participants 18 years of age and older in the United States. Randomization was stratified by age and health risk: 18 to <65 years of age without comorbidities (not at risk for progression to severe COVID-19), 18 to <65 years of age with comorbidities (at risk for progression to severe COVID-19), and 65 years of age and older with or without comorbidities. Participants who were immunocompromised and those with a known history of SARS-CoV-2 infection were excluded from the study. Participants with no known history of SARS-CoV-2 infection but with positive laboratory results indicative of infection at study entry were included. The study allowed for the inclusion of participants with stable pre-existing medical conditions, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment, as well as participants with stable human immunodeficiency virus (HIV) infection. A total of 30,415 participants were randomized equally to receive 2 doses of Moderna COVID-19 Vaccine or saline placebo 1 month apart. Participants will be followed for efficacy and safety until 2 years after the second dose.

The primary efficacy analysis population (referred to as the Per-Protocol Set) included 28,451 participants who received two doses (at 0 and 1 month) of either Moderna COVID-19 Vaccine (100 mcg mRNA per dose; n=14,287) or placebo (n=14,164), and had a negative baseline SARS-CoV-2 status. In the Per-Protocol Set, 47.5% of participants were female, 19.7% were Hispanic or Latino; 79.7% were White, 9.7% were African American, 4.7% were Asian, and 2.0% other races. The median age of participants was 53 years (range 18-95) and 25.4% of participants were 65 years of age and older. Of the study participants in the Per-Protocol Set, 22.8% were at increased risk of severe COVID-19 due to at least one pre-existing medical condition (chronic lung disease, significant cardiac disease, severe obesity, diabetes, liver disease, or HIV infection) regardless of age. There were no notable differences in demographics or pre-existing medical conditions between participants who received Moderna COVID-19 Vaccine and those who received placebo.

The population for the vaccine efficacy analysis included participants 18 years of age and older who were enrolled from July 27, 2020, and followed for the development of COVID-19 through the data cutoff of March 26, 2021, or the Participant Decision Visit for treatment unblinding, whichever was earlier. The median length of follow-up for participants in the blinded placebo-controlled phase of the study was 4 months following Dose 2.

Efficacy Against COVID-19

COVID-19 was defined based on the following criteria: The participant must have experienced at least two of the following systemic symptoms: fever (≥38ºC / ≥100.4ºF), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or the participant must have experienced at least one of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia; and the participant must have at least one NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR. COVID-19 cases were adjudicated by a Clinical Adjudication Committee.

There were 55 COVID-19 cases in the Moderna COVID-19 Vaccine group and 744 cases in the placebo group, with a vaccine efficacy of 93.2% (95% confidence interval of 91.0% to 94.8%) (Table 10).

SARS-CoV-2 identified in the majority of COVID-19 cases in this study were sequenced to be the B.1.2 variant. Additional SARS-CoV-2 variants identified in this study included B.1.427/B.1.429 (Epsilon), P.1 (Gamma), and P.2 (Zeta). Representation of identified variants among cases in the vaccine versus placebo recipients did not suggest decreased vaccine effectiveness against these variants.

Table 10: Vaccine Efficacy Against COVID-19* in Participants 18 Years of Age and Older Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per-Protocol Set

Severe COVID-19 was defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition, plus any of the following: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic blood pressure <90 mmHg, diastolic BP <60 mmHg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death.

Among all participants in the Per-Protocol Set analysis, which included COVID-19 cases confirmed by an adjudication committee, 2 cases of severe COVID-19 were reported in the Moderna COVID-19 Vaccine group compared with 106 cases reported in the placebo group, with a vaccine efficacy of 98.2% (95% confidence interval of 92.8% to 99.6%) (Table 11).

Table 11: Vaccine Efficacy Against Severe COVID-19* in Participants 18 Years of Age and Older Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per-Protocol Set

In an exploratory analysis, occurrence of asymptomatic SARS-CoV-2 infection was assessed among participants in the Per-Protocol Set (enrolled from July 27, 2020, and followed maximally through March 26, 2021). Asymptomatic SARS-CoV-2 infection was defined as having a positive scheduled serology test based on binding antibody against SARS-CoV-2 nucleocapsid protein as measured by the Roche Elecsys immunoassay (N-serology) and/or a positive RT-PCR test for SARS-CoV-2, in the absence of any reported COVID-19 symptoms included as part of the primary efficacy endpoint case definition (described above) or symptoms included in the secondary COVID-19 endpoint case definition (fever >38°C / ≥100.4°F, chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches, body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, or diarrhea) at any time during the study. To assess for asymptomatic infection starting 14 days after Dose 2, all participants had scheduled blood draws for N-serology collected at the 1-month post-Dose 2 visit and the 6-month post-Dose 2 visit (if still blinded to treatment arm), and scheduled N-serology and nasopharyngeal swab for RT-PCR collection at the Participant Decision Visit for treatment unblinding.

In the Per-Protocol Set, 14,287 participants in the Moderna COVID-19 Vaccine group and 14,164 participants in the placebo group had N-serology and/or RT-PCR results available from one or more of the pre-specified timepoints listed above. Among these participants, there were 180 cases of asymptomatic SARS-CoV-2 infection in the Moderna COVID-19 Vaccine group compared with 399 cases in the placebo group. Limitations of this analysis include the infrequently scheduled assessments for serology and PCR testing, which may not have captured all cases of asymptomatic infections which occurred during the study.

14.2 Effectiveness of Two-Dose Primary Series of Moderna COVID-19 Vaccine (Original Monovalent) in Participants 12 Years Through 17 Years of Age

Study 3 is an ongoing Phase 3 clinical trial with multiple parts. The randomized, placebo-controlled, observer-blind phase evaluated the safety, reactogenicity, and effectiveness of Moderna COVID-19 Vaccine in participants ages 12 years through 17 years in the United States. Participants with a known history of SARS-CoV-2 infection were excluded from the study. A total of 3,733 participants were randomized 2:1 to receive 2 doses of Moderna COVID-19 Vaccine (100 mcg mRNA per dose) or saline placebo 1 month apart. Among participants assessed for immunogenicity, 52.4% of participants were male, 47.6% were female, 7.6% were Hispanic or Latino; 83.5% were White, 1.2% were African American, 4.4% were Asian, 0.3% were Native Hawaiian or Pacific Islander, 2.1% were other races, and 5.6% were Multiracial.

Effectiveness in individuals 12 years through 17 years of age is based on a comparison of immune responses in this age group to adults 18 years through 25 years of age.

In Study 3, an analysis was conducted of SARS-CoV-2 50% neutralizing titers and seroresponse rates 28 days after Dose 2 in a subset of participants 12 years through 17 years of age in Study 3 and participants 18 years through 25 years of age in Study 1 who had no immunologic or virologic evidence of prior SARS-CoV-2 at baseline. Noninferior immune responses as assessed by geometric mean 50% neutralizing titers and seroresponse rates were demonstrated in a comparison of participants 12 years through 17 years of age to participants 18 years through 25 years of age (Table 12).

Table 12: Comparison of Geometric Mean Titer Ratio and Seroresponse Rate Against a Pseudovirus Expressing the Original SARS-CoV-2 Spike Protein (D614G) at 28 Days After Completion of the Primary Series of Moderna COVID-19 Vaccine,* Participants 12 Years Through 17 Years of Age vs Participants 18 Years Through 25 Years of Age – Per-Protocol Immunogenicity Subset

A descriptive efficacy analysis evaluating confirmed COVID-19 cases accrued up to the blinded data cutoff date of May 31, 2021, was performed in 3,186 participants who received two doses (at 0 and 1 month) of either Moderna COVID-19 Vaccine (n=2,142) or placebo (n=1,044) and had a negative baseline SARS-CoV-2 status (referred to as the Per-Protocol Set for Efficacy). In the Per-Protocol Set for Efficacy, 51.5% were male, 48.5% were female, 11.0% were Hispanic or Latino; 84.0% were White, 2.7% were African American, 6.2% were Asian, 0.5% were American Indian or Alaska Native, <0.1% were Native Hawaiian or Pacific Islander, 0.9% were other races, and 4.8% were Multiracial. There were no notable differences in demographics between participants who received Moderna COVID-19 Vaccine and those who received placebo.

The population for the vaccine efficacy analysis included participants 12 years through 17 years of age who were enrolled from December 9, 2020, and followed for the development of COVID-19 through the data cutoff of May 31, 2021. The median length of follow-up for participants in the blinded, placebo-controlled phase of the study was 112 days following Dose 2.

The efficacy information in participants 12 years through 17 years of age is presented in Table 13.

Table 13: Efficacy Analyses: COVID-19 in Participants 12 Years Through 17 Years of Age Starting 14 Days After Dose 2 – Per-Protocol Set for Efficacy

14.3 Effectiveness of Two-Dose Primary Series of Moderna COVID-19 Vaccine (Original Monovalent) in Participants 6 Years Through 11 Years of Age

Study 4 includes an ongoing Phase 2/3 randomized, placebo-controlled, observer-blind clinical trial component to evaluate the safety, reactogenicity, and effectiveness of Moderna COVID-19 Vaccine in individuals ages 6 years through 11 years in the United States and Canada (NCT04796896). Participants with a known history of SARS-CoV-2 infection within 2 weeks of study vaccination were excluded from the study. A total of 4,016 participants were randomized 3:1 to receive 2 doses of Moderna COVID-19 Vaccine (50 mcg mRNA per dose) or saline placebo 1 month apart. Participants will be followed for occurrence of COVID-19 and safety until 1 year after the last dose.

Effectiveness in individuals 6 years through 11 years of age is based on a comparison of immune responses in this age group to adults 18 years through 25 years of age.

In Study 4, an analysis was conducted of SARS-CoV-2 50% neutralizing titers and seroresponse rates 28 days after Dose 2 in a subset of individuals 6 years through 11 years of age in Study 4 and participants 18 years through 25 years of age in Study 1 who had no immunologic or virologic evidence of prior SARS-CoV-2 at baseline. Noninferior immune responses as assessed by geometric mean 50% neutralizing titers and seroresponse rates were demonstrated in a comparison of individuals 6 years through 11 years of age to participants 18 years through 25 years of age (Table 14).

Table 14: Summary of Geometric Mean Titer Ratio and Seroresponse Rate – Comparison of Individuals 6 Years Through 11 Years of Age to Participants 18 Years Through 25 Years of Age – Per-Protocol Immunogenicity Set

In a descriptive analysis, vaccine efficacy could not be determined reliably. An insufficient number of COVID-19 cases were accrued in the Per-Protocol population starting 14 days after Dose 2 due to treatment unblinding and cross-over vaccination after the availability of an authorized COVID-19 vaccine in this age group.

14.4 Effectiveness of Two-Dose Primary Series of Moderna COVID-19 Vaccine (Original Monovalent) in Participants 6 Months Through 5 Years of Age

Study 4 includes an ongoing Phase 2/3 randomized, placebo-controlled, observer-blind clinical trial component to evaluate the safety, reactogenicity, and effectiveness of Moderna COVID-19 Vaccine in individuals ages 6 months through 5 years in the United States and Canada (NCT04796896). Participants with a known history of SARS-CoV-2 infection within 2 weeks of study vaccination were excluded from the study. A total of 6,403 participants were randomized 3:1 to receive 2 doses of the Moderna COVID-19 Vaccine (25 mcg mRNA per dose) or saline placebo 1 month apart. Participants will be followed for occurrence of COVID-19 and safety until 1 year after the last dose.

Effectiveness in individuals 6 months through 5 years of age is based on a comparison of immune responses in this age group to adults 18 years through 25 years of age.

In Study 4, an analysis was conducted of SARS-CoV-2 neutralizing antibody concentrations and seroresponse rates 28 days after Dose 2 in a subset of individuals 6 months through 5 years of age in Study 4 and participants 18 years through 25 years of age in Study 1 who had no immunologic or virologic evidence of prior SARS-CoV-2 at baseline. Noninferior immune responses as assessed by neutralizing antibody concentrations in arbitrary units (AU)/mL and seroresponse rates were demonstrated in a comparison of individuals 6 months through 23 months of age to participants 18 years through 25 years of age (Table 15) and 2 years through 5 years of age to participants 18 years through 25 years of age (Table 16).

Table 15: Summary of Geometric Mean Concentration Ratio and Seroresponse Rate – Comparison of Individuals 6 Months Through 23 Months of Age to Participants 18 Years Through 25 Years of Age – Per-Protocol Immunogenicity Set

Table 16: Summary of Geometric Mean Concentration Ratio and Seroresponse Rate – Comparison of Individuals 2 Years Through 5 Years of Age to Participants 18 Years Through 25 Years of Age – Per-Protocol Immunogenicity Set

A descriptive efficacy analysis evaluating confirmed COVID-19 cases accrued up to the data cutoff date February 21, 2022, was performed in 5,476 participants 6 months through 5 years of age who received two doses (at 0 and 1 month) of either Moderna COVID-19 Vaccine or placebo and had a negative baseline SARS-CoV-2 status (referred to as the Per-Protocol Set for Efficacy) (for participants 6 months through 23 months, vaccine=1,511, placebo=513; for participants 2 years through 5 years, vaccine=2,594, placebo=858). For participants 6 months through 23 months in the Per-Protocol Set for Efficacy, 51.2% were male, 48.8% were female, 12.7% were Hispanic or Latino; 78.9% were White, 3.1% were African American, 4.6% were Asian, 0.2% were American Indian or Alaska Native, 0.0% were Native Hawaiian or Pacific Islander, 1.8% were other races, and 10.7% were Multiracial. For participants 2 years through 5 years, 50.7% were male, 49.3% were female, 14.0% were Hispanic or Latino, 76.8% were White, 4.1% were African American, 6.1% were Asian, 0.4% were American Indian or Alaska Native, 0.3% were Native Hawaiian or Pacific Islander, 1.6% were other races, and 10.3% were Multiracial. Between participants who received Moderna COVID-19 Vaccine and those who received placebo, there were no notable differences in demographics.

The median length of follow-up for efficacy post-Dose 2 was 68 days for participants 6 months through 23 months of age and 71 days for participants 2 years through 5 years of age.

Vaccine efficacy among individuals 6 months through 5 years of age in Study 4 was evaluated during the period when the B.1.1.529 (Omicron) variant was the predominant variant in circulation.

The efficacy information in individuals 6 months through 23 months of age and 2 years through 5 years of age are presented in Table 17 and Table 18, respectively.

Table 17: Efficacy Analyses: COVID-19 in Participants 6 Months Through 23 Months of Age Starting 14 Days After Dose 2 – Per Protocol Set for Efficacy

Table 18: Efficacy Analyses: COVID-19 in Participants 2 Years Through 5 Years of Age Starting 14 Days After Dose 2 – Per-Protocol Set for Efficacy

14.5 Immunogenicity of Moderna COVID-19 Vaccine (Original Monovalent) Booster Dose Following Moderna COVID-19 Vaccine (Original Monovalent) Primary Series in Participants 6 Years Through 11 Years of Age

Effectiveness of a booster dose of Moderna COVID-19 Vaccine in participants 6 years through 11 years of age was based on a comparison of immune responses, as assessed by neutralizing antibody concentration against a pseudovirus expressing the SARS-CoV-2 Spike protein from a USA_WA1/2020 isolate carrying the D614G mutation, following the booster dose in this age group to that following the primary series in adults 18 years through 25 years.

In an open-label phase of Study 4, participants 6 years through 11 years of age received a single booster dose of Moderna COVID-19 Vaccine (25 mcg mRNA) at least 6 months after completion of the primary series (two doses 1 month apart). The primary immunogenicity analysis population included 95 booster dose participants in Study 4 and a random subset of 295 participants 18 years through 25 years of age from Study 1 who received two doses of Moderna COVID-19 Vaccine 1 month apart. Study 1 and Study 4 participants included in the analysis population had no serologic or virologic evidence of SARS-CoV-2 infection prior to the first primary series dose and prior to the booster dose, respectively. Among participants 6 years through 11 years of age assessed for immunogenicity, 48.4% were male, 51.6% were female, 15.8% were Hispanic or Latino; 76.8% were White, 5.3% were Black or African American, 5.3% were Asian, 1.1% were American Indian or Alaskan Native, 1.1% were Native Hawaiian or Pacific Islander, 0.0% were other races, and 7.4% were Multiracial.

The primary immunogenicity analyses of the GMC ratio and difference in seroresponse rates following the booster dose in Study 4 compared to following the primary series in Study 1 met the pre-defined immunobridging success criteria. Seroresponse for a participant was defined as achieving a ≥4-fold rise of neutralizing antibody concentration from baseline (before the first dose of the primary series in Study 4 and Study 1). These analyses are summarized in Table 19.

Table 19: Comparison of Geometric Mean Concentration and Seroresponse Rate Against a Pseudovirus Expressing the SARS-CoV-2 Spike Protein (USA_WA1/2020 isolate carrying the D614G mutation) at 28 Days After a Booster Dose in Study 4 (Participants 6 Years Through 11 Years of Age) vs 28 Days After Completion of the Primary Series in Study 1 (Participants 18 Years Through 25 Years of Age) – Per-Protocol Immunogenicity Subsets

A descriptive analysis evaluated seroresponse rates using pre-booster neutralizing antibody concentration. The booster dose seroresponse rate, with seroresponse defined as at least a 4-fold rise relative to the pre-booster concentration, was 92.6%. The difference in seroresponse rates in this post-hoc analysis was -6.7% (95% CI -13.8, -2.7).

14.6 Immunogenicity of Moderna COVID-19 Vaccine (Original Monovalent) Booster Dose Following Moderna COVID-19 Vaccine (Original Monovalent) Primary Series in Participants 17 Months Through 5 Years of Age

Effectiveness of a booster dose of Moderna COVID-19 Vaccine in individuals 6 months through 5 years of age is based on a comparison of immune responses, as assessed by neutralizing antibody concentration against a pseudovirus expressing the SARS-CoV-2 Spike protein from a USA_WA1/2020 isolate carrying the D614G mutation, following the booster dose in study participants 17 months through 5 years of age to that following the primary series in adults 18 years through 25 years of age.

In an open-label phase of Study 4, participants 17 months through 5 years of age received a single booster dose of Moderna COVID-19 Vaccine (10 mcg mRNA) at least 6 months after completion of a Moderna COVID-19 Vaccine primary series (two doses 1 month apart). The primary immunogenicity analysis population included 56 booster dose participants in Study 4 and a random subset of 295 participants 18 years through 25 years of age from Study 1 who had completed primary vaccination with two doses of Moderna COVID-19 Vaccine (100 mcg mRNA per dose) 1 month apart. Study 1 and Study 4 participants included in the analysis population had no serologic or virologic evidence of SARS-CoV-2 infection prior to the first primary series dose and prior to the booster dose, respectively. Among participants 17 months through 5 years of age assessed for immunogenicity, 50.0% were male, 50.0% were female, 7.1% were Hispanic or Latino; 78.6% were White, 1.8% were Black or African American, 7.1% were Asian, 0.0% were American Indian or Alaskan Native, 0.0% were Native Hawaiian or Pacific Islander, 3.6% were other races, and 8.9% were Multiracial. Among the 56 participants in the primary immunogenicity analysis population, the median age for receipt of the booster dose was 2.3 years (range 1.4-5.6 years).

The primary immunogenicity analyses of the GMC ratio and difference in seroresponse rates following the booster dose in Study 4 compared to following the primary series in Study 1 met the pre-defined immunobridging success criteria. Seroresponse for a participant was defined as achieving a ≥4-fold rise of neutralizing antibody concentration from baseline (before the first dose of the primary series in Study 4 and Study 1). These analyses are summarized in Table 20.

Table 20: Comparison of Geometric Mean Concentration and Seroresponse Rate Against a Pseudovirus Expressing the SARS-CoV-2 Spike Protein (USA_WA1/2020 isolate carrying the D614G mutation) at 28 Days After a Booster Dose in Study 4 (Participants 17 Months Through 5 Years of Age) vs 28 Days After Completion of the Primary Series in Study 1 (Participants 18 Years Through 25 Years of Age) – Per-Protocol Immunogenicity Subsets

In a descriptive analysis, the booster dose seroresponse rate among participants 17 months through 5 years of age, with seroresponse defined as at least a 4-fold rise relative to the pre-booster concentration, was 94.6%. The difference in seroresponse rates (Study 4 participants minus Study 1 participants) in this post-hoc analysis was -4.7% (95% CI -14.0, -0.9).

14.7 Immunogenicity of Moderna COVID-19 Vaccine Administered as a First Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine

Effectiveness of a Moderna COVID-19 Vaccine booster dose in individuals who completed primary vaccination with another authorized or approved COVID-19 vaccine (heterologous booster dose) is inferred from immunogenicity data supporting effectiveness of a Moderna COVID-19 Vaccine booster dose administered following completion of a Moderna COVID-19 Vaccine primary series and from immunogenicity data from an independent Phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States that evaluated a booster dose of the Moderna COVID-19 Vaccine. The booster dose that study participants received contained twice the amount of mRNA compared to the authorized booster dose of the Moderna COVID-19 Vaccine. In this study, adults who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks (range 12 to 20 weeks) prior to enrollment and who reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of one of three vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine. Neutralizing antibody titers, as measured by a pseudovirus neutralization assay using a lentivirus expressing the SARS-CoV-2 Spike protein with D614G mutation, were assessed on Day 1 prior to administration of the booster dose and on Day 15 after the booster dose. A booster response to the Moderna COVID-19 Vaccine was demonstrated regardless of the vaccine used for primary vaccination.

14.8 Immunogenicity of Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose in Participants 18 Years of Age and Older

Study 5 is a Phase 2/3 open-label study in which participants 18 years of age and older, who had previously received a two-dose primary series and one booster dose of Moderna COVID-19 Vaccine, received a second booster dose with the bivalent vaccine (Original and Omicron BA.1) at least 3 months after the first booster dose. The bivalent vaccine (Original and Omicron BA.1) contained a total of 50 mcg mRNA per dose. The primary immunogenicity analysis population included 334 participants who received a booster dose of bivalent vaccine (Original and Omicron BA.1) and 260 participants who received a booster dose of Moderna COVID-19 Vaccine. Participants included in the analysis population had no serologic or virologic evidence of SARS-CoV-2 infection prior to the second booster dose.

Among participants assessed for immunogenicity, the median age of the population was 62 years (range 20-96). For the bivalent vaccine (Original and Omicron BA.1) group, 195 (58.4%) participants were age 18 years through 64 years of age and 139 (41.6%) were 65 years of age and older; 43.4% were male, 56.6% were female, 7.2% were Hispanic or Latino, 87.1% were White, 7.2% were African American, 3.3% were Asian, 0.0% were American Indian or Alaska Native, 0.0% were Native Hawaiian or Pacific Islander, 0.6% were other races, and 1.8% were Multiracial. For the Moderna COVID-19 Vaccine group, 140 (53.8%) of participants were age 18 years through 64 years of age and 120 (46.2%) were 65 years of age and older; 48.5% of participants were male, 51.5% were female, 8.5% were Hispanic or Latino, 90.0% were White, 4.2% were African American, 4.2% were Asian, 0.0% were American Indian or Alaska Native, 0.0% were Native Hawaiian or Pacific Islander, 0.4% were other races, and 0.0% were Multiracial. Demographic characteristics were similar among participants who received bivalent vaccine (Original and Omicron BA.1) and those who received Moderna COVID-19 Vaccine.

In Study 5, the neutralizing antibody titers (50% inhibitory dose [ID50]) against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G) and a pseudovirus expressing the Omicron BA.1 Spike protein were evaluated. Primary immunogenicity analyses compared the ID50 GMTs and seroresponse rates (the proportion achieving a ≥4-fold rise in ID50 from pre-dose 1 of the primary series) 28 days following a second booster dose with bivalent vaccine (Original and Omicron BA.1) to those following a second booster dose with Moderna COVID-19 Vaccine. Analyses of GMTs met predefined success criteria for superiority against Omicron BA.1 and noninferiority against the Original strain. The analysis of seroresponse against Omicron BA.1 met the criterion for noninferiority: Lower limit of the 2-sided 97.5% CI for the percentage difference in seroresponse rate (bivalent vaccine [Original and Omicron BA.1] minus Moderna COVID-19 Vaccine) >-10%. Table 21 presents the analyses of ID50 GMTs; the primary analysis of seroresponse is not shown.

Post-hoc analyses evaluated the differences in seroresponse rates (the proportion achieving a ≥4-fold rise in ID50 from pre-second booster) against both the Original strain and Omicron BA.1 (Table 22).

Table 21: Neutralizing Antibody Titers (ID50) at 28 Days After a Second Booster Dose with Bivalent Vaccine (Original and Omicron BA.1) or Moderna COVID-19 Vaccine in Participants 18 Years of Age and Older – Per-Protocol Immunogenicity SARS-CoV-2 Negative Set*

Table 22: Post-hoc Analyses of Seroresponse Rates at 28 Days After a Second Booster Dose with Bivalent Vaccine (Original and Omicron BA.1) or Moderna COVID-19 Vaccine in Participants 18 Years of Age and Older – Per-Protocol Immunogenicity SARS-CoV-2 Negative Set*

14.9 Immunogenicity of a Single Dose of Moderna COVID-19 Vaccine (Original Monovalent) in Participants 6 Years of Age and Older with Evidence of Prior SARS-CoV-2 Infection

Seroprevalence surveys estimate that almost all of the U.S. population 5 years of age and older now have antibodies (from vaccination and/or infection) against SARS-CoV-2 (Centers for Disease Control and Prevention. COVID Data Tracker. Atlanta, GA: US Department of Health and Human Services, CDC; 2023, March 31. https://covid.cdc.gov/covid-data-tracker).

A comparison of neutralizing antibody titers against a pseudovirus expressing the original SARS-CoV-2 Spike protein (D614G) at baseline (pre-Dose 1), at 28 days after Dose 1 for participants with evidence of prior SARS-CoV-2 infection, and at 28 days after Dose 2 for participants without evidence of prior SARS-CoV-2 infection from clinical studies evaluating a primary series of Moderna COVID-19 Vaccine is shown in Table 23 for the following age groups: 6 years through 11 years of age and 18 years of age and older. In both age groups, neutralizing antibody titers at 28 days post-Dose 1 in participants with evidence of prior infection were not statistically different from those of participants without evidence of prior infection at 28 days post-Dose 2. The effectiveness of a single dose of Moderna COVID-19 Vaccine in individuals 5 years of age with prior evidence of infection is extrapolated from these data in participants 6 years through 11 years of age.

Table 23: Geometric Mean Antibody Titers Against a Pseudovirus Expressing the SARS-CoV-2 Spike Protein (USA_WA1/2020 isolate carrying the D614G mutation) 28 Days Post-Dose 1 of Moderna COVID-19 Vaccine in Participants With Evidence of Prior SARS-CoV-2 Infection and 28 Days Post-Dose 2 of Moderna COVID-19 Vaccine in Participants Without Evidence of Prior SARS-CoV-2 Infection

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Moderna COVID-19 Vaccine (2023-2024 Formula): single dose vials with dark blue caps and labels with a green box.

NDC 80777-287-92                    Carton of 10 single dose vials

NDC 80777-287-07                    Single dose vial

Storage and Handling

Minimize exposure to room light and avoid exposure to direct sunlight and ultraviolet light.

Frozen Storage

Storage after Thawing

Do not refreeze once thawed.

Thawed vials can be handled in room light conditions.

Transportation of Thawed Vials at 2°C to 8°C (36°F to 46°F)

If transport at -50°C to -15°C (-58°F to 5°F) is not feasible, available data support transportation of one or more thawed vials for up to 12 hours at 2°C to 8°C (36°F to 46°F) when shipped using shipping containers which have been qualified to maintain 2°C to 8°C (36°F to 46°F) and under routine road and air transport conditions with shaking and vibration minimized. Once thawed and transported at 2°C to 8°C (36°F to 46°F), vials should not be refrozen and should be stored at 2°C to 8°C (36°F to 46°F) until use.

• •Store frozen between -50°C to -15°C (-58°F to 5°F).

17 PATIENT COUNSELING INFORMATION

Advise the recipient or caregiver to read the Fact Sheet for Recipients and Caregivers.

The vaccination provider must include vaccination information in the state/local jurisdiction’s Immunization Information System (IIS) or other designated system. Advise recipient or caregiver that more information about IISs can be found at: https://www.cdc.gov/vaccines/programs/iis/about.html.

18 MANUFACTURER INFORMATION

For general questions, send an email or call the telephone number provided below.

This EUA Prescribing Information may have been updated. For the most recent Full EUA Prescribing Information, please visit www.modernatx.com/covid19vaccine-eua.

Moderna US, Inc.Princeton, NJ 08540

©2023 ModernaTX, Inc. All rights reserved.Patent(s): www.modernatx.com/patentsRevised: Nov/1/2023

SPL UNCLASSIFIED SECTION

FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUTMODERNA COVID-19 VACCINE (2023-2024 FORMULA)WHICH HAS EMERGENCY USE AUTHORIZATION (EUA) TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) IN INDIVIDUALS 6 MONTHS THROUGH 11 YEARS OF AGE

Your child is being offered Moderna COVID-19 Vaccine (2023-2024 Formula) Moderna COVID-19 Vaccine (2023-2024 Formula) encodes the spike protein of the Omicron XBB.1.5 SARS-CoV-2. to prevent coronavirus disease 2019 (COVID-19), which is caused by the virus SARS-CoV-2. This fact sheet contains information to help you understand the risks and benefits of Moderna COVID-19 Vaccine (2023-2024 Formula), hereafter referred to as Moderna COVID-19 Vaccine, which your child may receive because there is currently a pandemic of COVID-19. Talk to your child’s vaccination provider if you have questions.

This Fact Sheet may have been updated. For the most recent Fact Sheet, please see www.modernatx.com/covid19vaccine-eua.

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to make Moderna COVID-19 Vaccine available during the COVID-19 pandemic (for more details about an EUA please see “What is an Emergency Use Authorization?” at the end of this document). Moderna COVID-19 Vaccine is not an FDA-approved vaccine for ages 6 months through 11 years of age in the United States. Read this Fact Sheet for information about Moderna COVID-19 Vaccine.

WHAT IS COVID-19?

COVID-19 is caused by a coronavirus called SARS-CoV-2. You can get COVID-19 through close contact with another person who has the virus.

It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have had a wide range of symptoms reported, ranging from mild symptoms to severe illness leading to death. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.

WHAT IS MODERNA COVID-19 VACCINE?

Moderna COVID-19 Vaccine is a vaccine for use in individuals 6 months through 11 years of age to prevent COVID-19. The FDA has authorized the emergency use of Moderna COVID-19 Vaccine under an EUA.

Moderna COVID-19 Vaccine may not protect everyone.

WHAT SHOULD YOU MENTION TO THE VACCCINATION PROVIDER BEFORE YOUR CHILD GETS MODERNA COVID-19 VACCINE?

Tell the vaccination provider about all of your child’s medical conditions, including if your child:

HOW IS THE VACCINE GIVEN?

Moderna COVID-19 Vaccine is given as an injection into the muscle.

Individuals 6 months through 4 years of age:

Individuals 5 years through 11 years of age:

Immunocompromised individuals 6 months through 11 years of age:

Additional doses of Moderna COVID-19 Vaccine may be administered. For more information, talk to your child’s healthcare provider.

WHO SHOULD NOT GET MODERNA COVID-19 VACCINE?

Your child should not get Moderna COVID-19 Vaccine if your child had:

WHAT ARE THE INGREDIENTS IN THIS VACCINE?

Moderna COVID-19 Vaccine contains the following ingredients: messenger ribonucleic acid (mRNA), lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate trihydrate, and sucrose.

HAS THIS VACCINE BEEN USED BEFORE?

Millions of individuals 6 months of age and older have received a Moderna COVID-19 vaccine under EUA. In clinical trials, approximately 5,000 individuals 6 months through 5 years of age, 4,000 individuals 6 years through 11 years of age, and 30,000 individuals 12 years of age and older have received at least 1 dose of Moderna COVID-19 Vaccine (Original monovalent).

The Moderna COVID-19 Vaccine is made in the same way as the Moderna COVID-19 Vaccine (Original monovalent) and Moderna COVID-19 Vaccine, Bivalent, but it encodes the spike protein of SARS-CoV-2 Omicron variant lineage XBB.1.5 (Omicron XBB.1.5).

WHAT ARE THE BENEFITS OF MODERNA COVID-19 VACCINE?

FDA has authorized Moderna COVID‑19 Vaccine to provide protection against COVID-19.

The duration of protection against COVID-19 is currently unknown.

WHAT ARE THE RISKS OF MODERNA COVID-19 VACCINE?

There is a remote chance that the vaccine could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose. For this reason, the vaccination provider may ask your child to stay at the place where your child received the vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include:

Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received mRNA COVID-19 vaccines. Myocarditis and pericarditis following Moderna COVID-19 vaccines have occurred most commonly in young adult males 18 years through 24 years of age. In most of these individuals, symptoms began within a few days following vaccination. The chance of having this occur is very low. You should seek medical attention right away if your child has any of the following symptoms after receiving the vaccine, particularly during the 2 weeks after your child receives a dose of the vaccine:

Additional symptoms, particularly in children, may include:

Side effects that have been reported in clinical trials with Moderna COVID-19 vaccines include:

Side effects that have been reported during post-authorization use include:

These may not be all the possible side effects. Serious and unexpected side effects may occur. The possible side effects are still being studied.

WHAT SHOULD I DO ABOUT SIDE EFFECTS?

If your child experiences a severe allergic reaction, call 9-1-1, or go to the nearest hospital.

Call the vaccination provider or your child’s healthcare provider if your child has any side effects that bother your child or do not go away.

Report vaccine side effects to FDA/CDC Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to https://vaers.hhs.gov/reportevent.html. Please include “Moderna COVID-19 Vaccine (2023-2024 Formula) EUA” in the first line of box #18 of the report form.

In addition, you can report side effects to ModernaTX, Inc. at 1-866-MODERNA (1-866-663-3762).

WHAT IF I DECIDE NOT TO HAVE MY CHILD GET MODERNA COVID-19 VACCINE?

Under the EUA, there is an option to accept or refuse receiving this vaccine. Should you decide for your child not to receive this vaccine, it will not change the standard medical care.

ARE THERE OTHER VACCINES FOR PREVENTING COVID-19 BESIDES MODERNA COVID-19 VACCINE?

Other vaccines to prevent COVID-19 may be available under EUA, including vaccines that encode the spike protein of the SARS-CoV-2 Omicron variant lineage XBB.1.5 (Omicron XBB.1.5).

CAN MY CHILD RECEIVE MODERNA COVID-19 VACCINE AT THE SAME TIME AS OTHER VACCINES?

Data have not yet been submitted to FDA on administration of Moderna COVID-19 Vaccine at the same time as other vaccines. If you are considering having your child receive Moderna COVID-19 Vaccine with other vaccines, discuss your options with your child’s healthcare provider.

WHAT IF MY CHILD IS IMMUNOCOMPROMISED?

Immunocompromised individuals 6 months through 11 years of age may receive additional doses of Moderna COVID-19 Vaccine (see HOW IS THE VACCINE GIVEN? above).

Vaccinations may not provide full immunity to COVID-19 in people who are immunocompromised; therefore, your child should continue to maintain physical precautions to help prevent COVID-19. Your child’s close contacts should be vaccinated as appropriate.

WHAT ABOUT PREGNANCY OR BREASTFEEDING?

If your child is pregnant or breastfeeding, discuss the options with your child’s healthcare provider.

WILL THIS VACCINE GIVE MY CHILD COVID-19?

No. This vaccine does not contain SARS-CoV-2 and cannot give your child COVID-19.

ADDITIONAL INFORMATION

If you have questions, visit the website or call the telephone number provided below.

To access the most recent Fact Sheets, please scan the QR code provided below.

HOW CAN I LEARN MORE?

WHERE WILL VACCINATION INFORMATION BE RECORDED?

The vaccination provider may include your child’s vaccination information in your state/local jurisdiction’s Immunization Information System (IIS) or other designated system. For more information about IISs, visit: https://www.cdc.gov/vaccines/programs/iis/about.html.

WHAT IS THE COUNTERMEASURES INJURY COMPENSATION PROGRAM?

The Countermeasures Injury Compensation Program (CICP) is a federal program that may help pay for costs of medical care and other specific expenses of certain people who have been seriously injured by certain medicines or vaccines, including this vaccine. Generally, a claim must be submitted to the CICP within one (1) year from the date of receiving the vaccine. To learn more about this program, visit www.hrsa.gov/cicp/ or call 1-855-266-2427.

WHAT IS AN EMERGENCY USE AUTHORIZATION (EUA)?

The FDA has made Moderna COVID-19 Vaccine available under an emergency access mechanism call an EUA. An EUA is supported by a Secretary of Health and Human Services (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. A product authorized for emergency use has not undergone the same type of review by FDA as an FDA-approved product.

FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, and available alternatives. In addition, the FDA decision is based on the totality of the scientific evidence available showing that the product may be effective to prevent COVID-19 during the COVID-19 pandemic and that the known and potential benefits of the product outweigh the known and potential risks of the product. All of these criteria must be met to allow for the product to be used under EUA during the COVID-19 pandemic.

The EUA is in effect for the duration of the COVID-19 EUA declaration justifying emergency use of this product, unless terminated or revoked (after which the product may no longer be used).

Moderna US, Inc.Princeton, NJ 08540

©2023 ModernaTX, Inc. All rights reserved.Patent(s): www.modernatx.com/patentsRevised: October/12/2023

• •has any allergies
• •has had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
• •has a fever
• •has a bleeding disorder or is on a blood thinner
• •is immunocompromised or is on a medicine that affects your child’s immune system
• •is pregnant
• •is breastfeeding
• •has received another COVID-19 vaccine
• •has ever fainted in association with an injection

Package/Label Display Panel

Moderna COVID-19 Vaccine

2023-2024 Formula

For Intramuscular Use

For use under EUA

For 6m through 11y

0.25 mL Single Dose Vial

Mfd. for: Moderna US, Inc.

NDC 80777-287-07

Package/Label Display Panel

NDC 80777-287-92

Moderna

Moderna COVID-19 Vaccine

Suspension for Intramuscular Injection

2023-2024 Formula

For use under Emergency Use Authorization

For 6 months through 11 years

STORE FROZEN between -50°C to -15°C (-58°F to 5°F)

Protect from light

10 Single Dose Vials

Each dose is 0.25 mL