Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
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Design
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Preliminary analysis of a randomized, observer-blinded, placebo-controlled, phase 3 clinical trial
N=28,207
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Objective
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To assess the safety and efficacy of the mRNA-1273 vaccine (Moderna vaccine) in preventing SARS-CoV-2 infection
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Study Groups
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Moderna Vaccine (n=14,134)
Placebo (n=14,073)
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Inclusion Criteria
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Aged ≥18 years, considered to be at high risk of SARS-CoV-2 infection (due to locations or circumstances), were healthy or had pre-existing medical conditions who are in stable condition (defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment), females with a negative pregnancy test, females and males who agreed to practice adequate contraception or has abstained from all activities that could result in pregnancy during the trial period
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Exclusion Criteria
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Persons who were acutely ill or febrile (≥38.0°C/100.4°F) 72 hours prior to screening; were pregnant or breastfeeding; had a known history of SARS-CoV-2 infection; had a history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine; had received or plans to receive a non-study vaccine within 28 days (except for seasonal influenza vaccine); had an immunosuppressive or immunodeficient state (including HIV infection, asplenia, and recurrent severe infections); received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (≥20 mg equivalents of prednisone per day); received systemic immunoglobulins or blood products within 3 months prior to screening
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Methods
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Participants were randomized 1:1 to receive two intramuscular injections of mRNA-1273 (100 μg/0.5 mL) or saline placebo 28 days apart. Group assignment was stratified based on age and COVID-19 risk criteria.
This is a preliminary, per-protocol analysis of participants who received both injections. Vaccine efficacy was defined as 1 - hazard ratio.
The vaccines were stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination. No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration.
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Duration
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July 27 to November 25, 2020 (interim analysis cut-off date)
Follow-up: up to 28 days post-injection
Long-term follow-up: up to 759 days post-injection
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Outcome Measures
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Safety: solicited and unsolicited local and systemic adverse events
Primary efficacy: a first occurrence of symptomatic COVID-19 with onset at least 14 days after the second injection
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Baseline Characteristics
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Placebo (n=14,073)
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Moderna Vaccine (n=14,134)
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Age, years (range)
18-65 years, not at risk
18-65 years, at risk
≥65 years
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51.6 (18-95)
8,200 (58.3%)
2,324 (16.5%)
3,549 (25.2%)
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51.6 (18-95)
8,189 (57.9%)
2,367 (16.7%)
3,578 (25.3%)
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Male
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7,432 (53%) |
7,366 (52.1%) |
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Body mass index, kg/m2
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29.27 ± 6.65 |
29.28 ± 6.83 |
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Risk factors for severe COVID-19
Chronic lung disease
Significant cardiac disease
Severe obesity
Diabetes
Liver disease
HIV
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4.9%
4.9%
6.7%
9.6%
0.6%
0.5%
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4.8%
5.0%
6.8%
9.7%
0.7%
0.6%
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Of the population, 79.5% were White and 79.3% did not identify as Hispanic or Latino. |
Results
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Placebo (n=14,073)
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Moderna Vaccine (n=14,134)
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Vaccine efficacy
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Symptomatic COVID-19 within 14 days of the second dose |
185 (65.5 per 1000 person-years) |
11 (3.3 per 1000 person-years) |
94.1% |
Severe COVID-19 |
30 (0.2%) |
0 |
100% |
COVID-19 after the first dose |
225 (1.6%) |
11 (0.078%) |
95.2% |
Any COVID-19 symptoms within 14 days of the second dose |
221 (1.6%) |
11 (0.078%) |
95.1% |
The primary efficacy endpoint corresponds to a vaccine efficacy of 94.1% (95% confidence interval [CI] 89.3% to 96.8%; P<0.001). Subgroup analyses of age groups (18-65 years and ≥65 years), presence of risk for severe Covid-19, sex, and race/ethnic group (non-Hispanic White and communities of color) showed consistent results.
Of the modified intention-to-treat population, 54 patients tested positive (via RT-PCR) for COVID-19 at the scheduled second dose (39 vs 15). This corresponds to a vaccine efficacy of 89.6% (95% CI 85.2% to 92.6%) in this population.
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Adverse Events
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Overall data set |
Placebo (n=15,166)
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Moderna Vaccine (n=15,185) |
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Any solicited AEs
After first injection
After second injection
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48.1%
42.8%
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87.8%
92.2%
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Injection-site pain
After first injection
After second injection
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17.5%
17.0%
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83.7%
88.2%
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Fatigue
After first injection
After second injection
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27.3%
23.3%
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37.2%
65.3%
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Other common solicited AEs: axillary swelling/tenderness, headache, myalgia, arthralgia, chills, nausea/vomiting
Solicited systemic adverse events in the mRNA-1273 group lasted a mean of 2.9 days and 3.1 days after the first and second doses, respectively.
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Any unsolicited AEs
Headache
Cough
Oropharyngeal pain
Diarrhea
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21.6%
30%
1.0%
1.3%
1.1%
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23.9%
3.1%
1.1%
1.0%
1.2%
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Hypersensitivity (any severity) |
1.1% |
1.5% |
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Both solicited injection-site and systemic adverse events were more common among younger participants (18 to 65 years) than among older participants (≥65 years).
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Study Author Conclusions
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The mRNA-1273 vaccine (Moderna Vaccine) showed 94.1% efficacy at preventing COVID-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.
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InpharmD Researcher Critique
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A large limitation of this analysis is the short duration of safety and efficacy follow-up, as the trial is still ongoing. The primary efficacy data was conducted in a per-protocol population, as the modified intention-to-treat population appeared to show a lower vaccine efficacy; however, this population had only received their first dose. While this data is promising, results from the full analysis will determine the true efficacy and safety of the Moderna COVID-19 Vaccine.
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