MODERNA COVID-19 VACCINE CX-024414 Suspension for injection Ref.[10624] Active ingredients: mRNA-1273

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 the 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 guidelines (https://www.cdc.gov/vaccines/covid-19/).

5.2 Altered Immunocompetence

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

5.3 Limitations of Vaccine Effectiveness

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

Overall safety summary

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of Multi-inflammatory Syndrome (MIS) in adults, and hospitalized or fatal cases of COVID-19 following vaccination with the Moderna COVID-19 Vaccine. To the extent feasible, provide a copy of the VAERS form to ModernaTX, Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details on reporting to VAERS and ModernaTX, Inc.

In clinical studies, the adverse reactions in participants 18 years of age and older were pain at the injection site (92.0%), fatigue (70.0%), headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23.0%), axillary swelling/tenderness (19.8%), fever (15.5%), swelling at the injection site (14.7%), and erythema at the injection site (10.0%).

Requirements and instructions for reporting adverse events and vaccine administration errors

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for the MANDATORY reporting of the listed events following Moderna COVID-19 Vaccine to the Vaccine Adverse Event Reporting System (VAERS)

• Vaccine administration errors whether or not associated with an adverse event
• Serious adverse events^* (irrespective of attribution to vaccination)
• Cases of multisystem inflammatory syndrome (MIS) in adults
• Cases of COVID-19 that results in hospitalization or death

^* Serious Adverse Events are defined as:

• Death;
• A life-threatening adverse event;
• Inpatient hospitalization or prolongation of existing hospitalization;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
• A congenital anomaly/birth defect;
• An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above.

Instructions for reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using one of the following methods:

• Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
• If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If you need additional help submitting a report, you may call the VAERS toll- free information line at 1-800-822-7967 or send an email to info@vaers.org.

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:

• Patient demographics (e.g., patient name, date of birth)
• Pertinent medical history
• Pertinent details regarding admission and course of illness
• Concomitant medications
• Timing of adverse event(s) in relationship to administration of Moderna COVID-19 Vaccine
• Pertinent laboratory and virology information
• Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

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

1. In Box 17, provide information on Moderna COVID-19 Vaccine and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within one month prior.
2. In Box 18, description of the event:
   1. Write “Moderna COVID-19 Vaccine EUA” as the first line
   2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
3. Contact information:
   1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
   2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
   3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider’s office address).

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.

Email: ModernaPV@modernatx.com
Fax number: 1-866-599-1342
Telephone number: 1-866-MODERNA

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.

Overall, 15,419 participants aged 18 years and older received at least one dose of Moderna COVID- 19 Vaccine in three clinical trials (NCT04283461, NCT04405076, and NCT04470427).

The safety of Moderna COVID-19 Vaccine was evaluated in an ongoing Phase 3 randomized, placebo-controlled, observer-blind clinical trial conducted in the United States involving 30,351 participants 18 years of age and older who received at least one dose of Moderna COVID-19 Vaccine (n=15,185) or placebo (n=15,166) (NCT04470427). At the time of vaccination, the mean age of the population was 52 years (range 18-95); 22,831 (75.2%) of participants were 18 to 64 years of age and 7,520 (24.8%) of participants were 65 years of age and older. Overall, 52.7% were male, 47.3% 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, 2.1% were Other, and 2.1% were Multiracial. Demographic characteristics were similar among participants who received Moderna COVID-19 Vaccine and those who received placebo.

Solicited Adverse Reactions

Data on solicited local and systemic adverse reactions and use of antipyretic medication were collected using standardized diary cards for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving Moderna COVID-19 Vaccine (n=15,179) and participants receiving placebo (n=15,163) with at least 1 documented dose. Solicited adverse reactions were reported more frequently among vaccine participants than placebo participants.

The reported number and percentage of the solicited local and systemic adverse reactions by age group and dose by subject are presented in Table 1 and Table 2, respectively.

Table 1. Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Within 7 Days^* After Each Dose in Participants 18-64 Years (Solicited Safety Set, Dose 1 and Dose 2):

^* 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
^a Placebo was a saline solution.
^b Grade 3 pain and axillary swelling/tenderness: Defined as any use of prescription pain reliever; prevents daily activity.
^c Grade 3 swelling and erythema: Defined as >100 mm / >10 cm.
^d Grade 3 fatigue, myalgia, arthralgia: Defined as significant; prevents daily activity.
^e Grade 4 fatigue, arthralgia: Defined as requires emergency room visit or hospitalization.
^f Grade 3 headache: Defined as significant; any use of prescription pain reliever or prevents daily activity.
^g Grade 3 chills: Defined as prevents daily activity and requires medical intervention.
^h Grade 3 nausea/vomiting: Defined as prevents daily activity, requires outpatient intravenous hydration.
ⁱ Grade 3 fever: Defined as ≥39.0 - ≤40.0°C / ≥102.1 - ≤104.0°F.
^j Grade 4 fever: Defined as >40.0°C / >104.0°F.

Table 2. Number and Percentage of Participants With Solicited Local and Systemic Adverse Reactions Within 7 Days^* After Each Dose in Participants 65 Years and Older (Solicited Safety Set, Dose 1 and Dose 2):

^* 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary).
^a Placebo was a saline solution.
^b Grade 3 pain and axillary swelling/tenderness: Defined as any use of prescription pain reliever; prevents daily activity.
^c Grade 3 swelling and erythema: Defined as >100 mm / >10 cm.
^d Grade 3 fatigue, myalgia, arthralgia: Defined as significant; prevents daily activity.
^e Grade 3 headache: Defined as significant; any use of prescription pain reliever or prevents daily activity.
^f Grade 3 chills: Defined as prevents daily activity and requires medical intervention.
^g Grade 3 Nausea/vomiting: Defined as prevents daily activity, requires outpatient intravenous hydration.
^h Grade 4 Nausea/vomiting: Defined as requires emergency room visit or hospitalization for hypotensive shock.
ⁱ Grade 3 fever: Defined as ≥39.0 - ≤40.0°C / ≥102.1 - ≤104.0°F.
^j Grade 4 fever: Defined as >40.0°C / >104.0°F.

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

Grade 3 solicited local adverse reactions were more frequently reported after Dose 2 than Dose 1. Solicited systemic adverse reactions were more frequently reported by vaccine recipients after Dose 2 than after Dose 1.

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 of 2 years. As of November 25, 2020, among participants who had received at least 1 dose of vaccine or placebo (vaccine=15,185, placebo=15,166), unsolicited adverse events that occurred within 28 days following each vaccination were reported by 23.9% of participants (n=3,632) who received Moderna COVID-19 Vaccine and 21.6% of participants (n=3,277) who received placebo. In these analyses, 87.9% of study participants had at least 28 days of follow-up after Dose 2.

Lymphadenopathy-related events that were not necessarily captured in the 7-day e-Diary were reported by 1.1% of vaccine recipients and 0.6% of placebo recipients. These events included lymphadenopathy, lymphadenitis, lymph node pain, vaccination-site lymphadenopathy, injection-site lymphadenopathy, and axillary mass, which were plausibly related to vaccination. This imbalance is consistent with the imbalance observed for solicited axillary swelling/tenderness in the injected arm.

Hypersensitivity adverse events were reported in 1.5% of vaccine recipients and 1.1% of placebo recipients. Hypersensitivity events in the vaccine group included injection site rash and injection site urticaria, which are likely related to vaccination.

Throughout the same period, there were three reports of Bell’s palsy in the Moderna COVID-19 Vaccine group (one of which was a serious adverse event), which occurred 22, 28, and 32 days after vaccination, and one in the placebo group which occurred 17 days after vaccination. Currently available information on Bell’s palsy 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

As of November 25, 2020, serious adverse events were reported by 1.0% (n=147) of participants who received Moderna COVID-19 Vaccine and 1.0% (n=153) of participants who received placebo, one of which was the case of Bell’s palsy which occurred 32 days following receipt of vaccine.

In these analyses, 87.9% of study participants had at least 28 days of follow-up after Dose 2, and the median follow-up time for all participants was 9 weeks after Dose 2.

There were two serious adverse events of facial swelling in vaccine recipients with a history of injection of dermatological fillers. The onset of swelling was reported 1 and 2 days, respectively, after vaccination and was likely related to vaccination.

There was one serious adverse event of intractable nausea and vomiting in a participant with prior history of severe headache and nausea requiring hospitalization. This event occurred 1 day after vaccination 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.

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

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Moderna COVID-19 Vaccine during pregnancy. Women 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 Moderna COVID-19 Vaccine administered to pregnant women 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 human dose of Moderna COVID-19 Vaccine 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.

Risk Summary

Data are not available to assess the effects of Moderna COVID-19 Vaccine on the breastfed infant or on milk production/excretion.

Safety and effectiveness have not been assessed in persons less than 18 years of age. Emergency Use Authorization of Moderna COVID-19 Vaccine does not include use in individuals younger than 18 years of age.

Clinical studies of Moderna COVID-19 Vaccine included participants 65 years of age and older receiving vaccine or placebo, and their data contribute to the overall assessment of safety and efficacy. In an ongoing Phase 3 clinical study, 24.8% (n=7,520) of participants were 65 years of age and older and 4.6% (n=1,399) of participants were 75 years of age and older. Vaccine efficacy in participants 65 years of age and older was 86.4% (95% CI 61.4, 95.2) compared to 95.6% (95% CI 90.6, 97.9) in participants 18 to <65 years of age [see Clinical Trial Results and Supporting Data for EUA (18)]. Overall, there were no notable differences in the safety profiles observed in participants 65 years of age and older and younger participants [see Clinical Trials Experience (6.1)].