Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Design

Preliminary analysis of a randomized, observer-blinded, placebo-controlled, phase 3 clinical trial

N=28,207

Objective

To assess the safety and efficacy of the mRNA-1273 vaccine (Moderna vaccine) in preventing SARS-CoV-2 infection

Study Groups

Moderna Vaccine (n=14,134)

Placebo (n=14,073)

Inclusion Criteria

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

Exclusion Criteria

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

Methods

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.

Duration

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

Outcome Measures

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

Baseline Characteristics

Placebo (n=14,073)

Moderna Vaccine (n=14,134)

Age, years (range)

18-65 years, not at risk

18-65 years, at risk

≥65 years

51.6 (18-95)

8,200 (58.3%)

2,324 (16.5%)

3,549 (25.2%)

51.6 (18-95)

8,189 (57.9%)

2,367 (16.7%)

3,578 (25.3%)

Male

Body mass index, kg/m²

Risk factors for severe COVID-19

Chronic lung disease

Significant cardiac disease

Severe obesity

Diabetes

Liver disease

HIV

4.9%

4.9%

6.7%

9.6%

0.6%

0.5%

4.8%

5.0%

6.8%

9.7%

0.7%

0.6%

Results

Placebo (n=14,073)

Moderna Vaccine (n=14,134)

Vaccine efficacy

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.

Adverse Events

Placebo (n=15,166)

Any solicited AEs

After first injection

After second injection

48.1%

42.8%

87.8%

92.2%

Injection-site pain

After first injection

After second injection

17.5%

17.0%

83.7%

88.2%

Fatigue

After first injection

After second injection

27.3%

23.3%

37.2%

65.3%

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.

Any unsolicited AEs

Headache

Cough

Oropharyngeal pain

Diarrhea

21.6%

30%

1.0%

1.3%

1.1%

23.9%

3.1%

1.1%

1.0%

1.2%

Both solicited injection-site and systemic adverse events were more common among younger participants (18 to 65 years) than among older participants (≥65 years).

Study Author Conclusions

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.

InpharmD Researcher Critique

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.