Peer-Review of the Phase 3 Study Moderna & NIAID Study Results: Unprecedented Accomplishment

Peer-Review of the Phase 3 Study Moderna & NIAID Study Results Unprecedented Accomplishment

The results of a Phase 3 clinical trial evaluating the COVID-19 vaccine known as mRNA-1273 were published in the peer-reviewed New England Journal of Medicine. The vaccine, co-developed by Moderna, Inc., the Cambridge, MA-based biotech company along with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National institutes of Health (NIH) was recently evaluated in the COVE trial. The peer-reviewed  findings confirm that no material safety concerns are prominent and that the vaccine, now approved under emergency authorization, shows a 94.1% efficacy rate in preventing SARS-CoV-2, the virus behind COVID-19. TrialSite echoes the authors’ conclusion that this vaccine is associated with unprecedented collaborative productivity: the pandemic led to a confluence of government, academic, medical and business interests leading to historical accomplishment in the field of vaccine development.  

This recent study was led by Lindsey R. Baden, M.D. of Brigham and Women’s Hospital in Boston, Hana M. El-Sahly, M.D. of Baylor College of Medicine in Houston, and Brandon Essink, M.D., of Meridian Clinical Research. The trial was implemented under the U.S. government’s Operation Warp Speed program and supported by NIAID and the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. The results can be accessed here: LR Baden, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2035389.  

The Study

The trial began on July 27, 2020, and enrolled 30,420 adult volunteers at clinical research sites across the United States. Volunteers were randomly assigned 1:1 to receive either two 100 microgram (mcg) doses of the investigational vaccine or two shots of saline placebo 28 days apart. The average age of volunteers is 51 years. Approximately 47% are female, 25% are 65 years or older and 17% are under the age of 65 with medical conditions placing them at higher risk for severe COVID-19. Approximately 79% of participants are white, 10% are Black or African American, 5% are Asian, 0.8% are American Indian or Alaska Native, 0.2% are Native Hawaiian or Other Pacific Islander, 2% are multiracial, and 21% (of any race) are Hispanic or Latino.

From the start of the trial through Nov. 25, 2020, investigators recorded 196 cases of symptomatic COVID-19 occurring among participants at least 14 days after they received their second shot. One hundred and eighty-five cases (30 of which were classified as severe COVID-19) occurred in the placebo group and 11 cases (0 of which were classified as severe COVID-19) occurred in the group receiving mRNA-1273. The incidence of symptomatic COVID-19 was 94.1% lower in those participants who received mRNA-1273 as compared to those receiving a placebo. 

The Results to Date

The research team observed 236 cases of symptomatic COVID-19 among participants at least 14 days after they received their first shot, with 225 cases in the placebo group and 11 cases in the group receiving mRNA-1273. The vaccine efficacy was 95.2% for this secondary analysis. 

No Safety Concerns Observed

There were no concerning safety issues with vaccination, according to the authors. Local reactions to the vaccine were generally mild. About 50% of participants receiving mRNA-1273 experienced moderate-to-severe side effects — such as fatigue, muscle aches, joint pain and headache — after the second dose, which resolved in most volunteers within two days.

No Evidence of Vaccine-Associated Enhanced Respiratory Disease (VAERD)

Investigators also observed no evidence of VAERD among those who received mRNA-1273. This rare complication was seen in individuals vaccinated with a whole-inactivated respiratory syncytial virus (RSV) vaccine in the 1960s, before there was a capacity to define protein structures and measure immune responses with precision. VAERD can occur when a vaccine induces an immune response that is not strong enough to protect against infection.

Not Sufficient Data to Declare if mRNA-1273 can Prevent Transmission

Although mRNA-1273 is highly efficacious in preventing symptomatic COVID-19, there is not yet enough available data to draw conclusions as to whether the vaccine can impact SARS-CoV-2 transmission. Preliminary trial data suggests there may be some degree of prevention of asymptomatic infection after a single dose. Additional analyses are underway of the incidence of asymptomatic infection and viral shedding post-infection to understand the vaccine’s impact on infectiousness.

Lead Research/Investigator

Lindsey R. Baden, M.D., Brigham and Women’s Hospital in Boston

Hana M. El-Sahly, M.D., Baylor College of Medicine in Houston

Brandon Essink, MD, Meridian Research

For other authors, check the source.

Call to Action: NIAID Director Anthony S. Fauci, M.D. is available to comment on this study. John R. Mascola, M.D., director of NIAID’s Vaccine Research Center, is also available to comment.