Randomized Controlled Trial
Study population and setting
This phase 2-3, randomized, placebo-controlled trial tested Moderna’s mRNA-1273 vaccine in healthy male and female adolescents ages 12-17 years old. The trial took place between December 9, 2020 and February 28, 2021 at 26 sites in the United States and included 3,732 participants. Participants were randomized 2:1 to either receive two doses of 100ug of mRNA-1273 or two doses of placebo 28 days apart. Primary objectives were safety of the vaccine, which was tracked through adverse events and data on multi-inflammatory syndrome in children (MIS-C) throughout the trial, and noninferiority of the immune response in the adolescent age group compared to the young adult (18-25) age group. Noninferiority was assessed by measuring neutralizing antibody titers 28 days after the second dose and comparing these values to those of the young adult group. A secondary aim of the study was to gain a preliminary assessment of vaccine efficacy against preventing COVID-19 or asymptomatic SARS-CoV-2, evaluated by PCR testing and clinical symptoms.
Summary of Main Findings
In the safety assessment, the most common solicited reaction was injection site pain after first dose. Other common systemic reactions included fatigue, headache, muscle pain, and chills. There was a higher incidence of adverse events in the vaccine group compared to the placebo group. Additionally, incidence of erythema, or skin redness, was higher in the adolescent group compared to young adults. No deaths, MIS-C or adverse events occurred in either group. The criteria for noninferiority of the immunogenicity were met for both objectives, and it was determined that the vaccine worked as well in adolescents as it does in young adults. Vaccine efficacy was estimated to be 93.3% using the CDC’s definition of COVID-19 with onset at least 14 days after the 2nd dose. For asymptomatic infection, vaccine efficacy was estimated to be 39.2% for the per protocol population, but this is consistent with other age groups in that efficacy against asymptomatic infection is lower than efficacy against symptomatic COVID-19.
This trial included a modest number of participants in an age group that has been sparsely studied in the realm of COVID-19 vaccines. The data from the adolescents in this study was compared to results from young adults in the phase 3 trial. Also, the young adults had similar demographic characteristics to the adolescents in this trial.
The trial population was less diverse, and therefore less representative of the US population, compared to the participants in the phase 3 trial. Over 80% of participants were white. Next, efficacy was difficult to assess here due to a very low incidence of COVID-19 in the participants, with only 4 cases in the placebo group and 0 cases in the vaccine group, therefore the authors used the CDC’s less stringent definition of COVID-19. There was also a relatively low number of asymptomatic cases, resulting in a negative lower boundary of the 95% confidence interval. Finally, safety data was based on assessments for a median of 83 days of follow-up, and therefore any longer-term effects cannot be determined from this study. Although it should be noted that there have been no long-term effects of the vaccine reported in previous trials suggesting this is not a concern.
First report of safety, immunogenicity, and efficacy results for Moderna’s mRNA-1273 vaccine in adolescents.
This review was posted on: 1 September 2021