- The Moderna COVID‑19 Vaccine has not been approved or licensed by the US Food and Drug Administration (FDA), but has been authorized for emergency use by FDA, under an Emergency Use Authorization (EUA), to prevent Coronavirus Disease 2019 (COVID‑19) for use in individuals 18 years of age and older. There is no FDA-approved vaccine to prevent COVID‑19.
- The EUA for the Moderna COVID‑19 Vaccine is in effect for the duration of the COVID‑19 EUA declaration justifying emergency use of the product, unless the declaration is terminated or the authorization is revoked sooner.
Clinical Trial Results
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.
Summary of Data from Phase 3 Clinical Trial
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.
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%).
Cases of COVID‑19, starting 14 days after Dose 2, were defined as symptomatic COVID‑19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom.
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.
Safety Analysis of Clinical Trial Data
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). 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%)
- Erythema at the injection site (10.0%).
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.
Patient Demographics in Clinical Trials
In the safety analysis of the Phase 3 clinical trial, at the time of vaccination, the mean age of the trial 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% of trial participants were male, and 47.3% were female.
Among trial participants in the safety analysis, 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.
Current Clinical Trials
Moderna COVID‑19 Vaccine is currently being investigated in a 3-phase clinical trial program.
Phase 1 Trial, Study P101 (NCT04283461)
- See the preliminary report published in New England Journal of Medicine
- Follow‑up evaluation of subjects in ongoing
- View phase 1 trial overview on ClinicalTrials.gov
Phase 2 Trial, Study P201 (NCT04405076)
- Study evaluation is ongoing
- View phase 2 trial overview on ClinicalTrials.gov