Moderna COVID-19 Vaccine: Package Insert and Label Information (Page 3 of 5)

6.2 Post-Authorization Experience

The following adverse reactions have been identified during post-authorization use of the Moderna COVID-19 Vaccine. 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

Nervous System Disorders: syncope

8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS

See Overall Safety Summary ( Section 6) for additional information.

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

Fax number

Telephone number

ModernaPV@modernatx.com

1-866-599-1342

1-866-MODERNA

(1-866-663-3762)

10 DRUG INTERACTIONS

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

11 USE IN SPECIFIC POPULATIONS

11.1 Pregnancy

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.

11.2 Lactation

Risk Summary

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

11.3 Pediatric Use

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.

11.4 Geriatric Use

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 Overall Safety Summary ( 6.1)] .

11.5 Use in Immunocompromised

Safety and effectiveness of a third dose of the Moderna COVID-19 Vaccine have been tested in persons that received solid organ transplants. The administration of third vaccine doses appears to be only moderately effective in increasing antibody titers, so patients should be counselled 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.

13 DESCRIPTION

Moderna COVID-19 Vaccine is provided as a white to off-white suspension for intramuscular injection. Each 0.5 mL dose of Moderna COVID-19 Vaccine contains 100 mcg of nucleoside-modified messenger RNA (mRNA) encoding the pre-fusion stabilized Spike glycoprotein (S) of SARS-CoV-2 virus.

Each dose of the Moderna COVID-19 Vaccine contains the following ingredients: a total lipid content of 1.93 mg (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), 0.31 mg tromethamine, 1.18 mg tromethamine hydrochloride, 0.043 mg acetic acid, 0.20 mg sodium acetate trihydrate, and 43.5 mg sucrose.

Moderna COVID-19 Vaccine does not contain a preservative.

The vial stoppers are not made with natural rubber latex.

14 CLINICAL PHARMACOLOGY

14.1 Mechanism of Action

The nucleoside-modified mRNA in the 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.

18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

A Phase 3 randomized, placebo-controlled, observer-blind clinical trial to evaluate the efficacy, safety, and immunogenicity of the Moderna COVID-19 Vaccine in participants 18 years of age and older is ongoing in the United States (NCT04470427). 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 30,420 participants were randomized equally to receive 2 doses of the Moderna COVID-19 Vaccine or saline placebo 1 month apart. Participants will be followed for efficacy and safety until 24 months after the second dose.

The primary efficacy analysis population (referred to as the Per-Protocol Set) included 28,207 participants who received two doses (at 0 and 1 month) of either Moderna COVID-19 Vaccine (n=14,134) or placebo (n=14,073), and had a negative baseline SARS-CoV-2 status. In the Per-Protocol Set, 47.4% were female, 19.7% were Hispanic or Latino; 79.5% were White, 9.7% were African American, 4.6% were Asian, and 2.1% other races. The median age of participants was 53 years (range 18-95) and 25.3% of participants were 65 years of age and older. Of the study participants in the Per-Protocol Set, 18.5% 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. Between participants who received Moderna COVID-19 Vaccine and those who received placebo, there were no notable differences in demographics or pre-existing medical conditions.

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), 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.

The median length of follow up for efficacy for participants in the study was 9 weeks post Dose 2. There were 11 COVID-19 cases in the Moderna COVID-19 Vaccine group and 185 cases in the placebo group, with a vaccine efficacy of 94.1% (95% confidence interval of 89.3% to 96.8%).

Table 3: Primary Efficacy Analysis: COVID-19* in Participants 18 Years of Age and Older Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per-Protocol Set
* COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom. Cases starting 14 days after Dose 2.  † VE and 95% CI from the stratified Cox proportional hazard model. 

Moderna COVID-19 Vaccine

Placebo

% Vaccine Efficacy (95% CI)†

Participants

(N)

COVID-19

Cases (n)

Incidence Rate of COVID-19

per 1,000 Person-Years

Participants

(N)

COVID-19

Cases (n)

Incidence Rate of COVID-19

per 1,000 Person-Years

14,134

11

3.328

14,073

185

56.510

94.1

(89.3, 96.8)

The subgroup analyses of vaccine efficacy are presented in Table 4.

Table 4: Subgroup Analyses of Vaccine Efficacy: COVID-19* Cases Starting 14 Days After Dose 2 per Adjudication Committee Assessments – Per- Protocol Set
* COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom. Cases starting 14 days after Dose 2. † VE and 95% CI from the stratified Cox proportional hazard model.

Age

Subgroup

(Years)

Moderna COVID-19 Vaccine

Placebo

% Vaccine Efficacy (95% CI)*

Participants

(N)

COVID-19

Cases

(n)

Incidence Rate of COVID-19 per 1,000 Person-Years

Participants

(N)

COVID-19

Cases

(n)

Incidence Rate of COVID-19

per 1,000 Person-Years

18 to <65

10,551

7

2.875

10,521

156

64.625

95.6

(90.6, 97.9)

≥65

3,583

4

4.595

3,552

29

33.728

86.4

(61.4, 95.2)

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, no cases of severe COVID-19 were reported in the Moderna COVID-19 Vaccine group compared with 30 cases reported in the placebo group (incidence rate 9.138 per 1,000 person-years). One PCR-positive case of severe COVID-19 in a vaccine recipient was awaiting adjudication at the time of the analysis.

A separate randomized-controlled study has been conducted in 120 individuals 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). A third dose of the Moderna COVID-19 Vaccine was administered to 60 individuals approximately 2 months after they had received a second dose; saline placebo was given to 60 individuals for comparison. Significant increases in levels of SARS-CoV-2 antibodies occurred four weeks after the third dose in 33/60 (55.0%) of the Moderna COVID-19 Vaccine group and 10/57 (17.5%) of the placebo group.

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