Randomized Controlled Trial
Study population and setting
This study reports on findings from an interim analysis of the randomized, double-blind, placebo-controlled phase 3 trial of Gam-COVID-Vac in Russia. Gam-COVID-Vac is an adenoviral based vaccine using both rAd5 and rAd26. The vaccine is given in a prime boost regimen: the first dose is with rAd26 encoding the SARS-CoV-2 glycoprotein S and the second dose is 21 days later with rAd5 encoding the SARS-CoV-2 glycoprotein S. The study included 977 healthy participants aged 18-87 years old. The primary outcome of the study was the number of patients with PCR-confirmed COVID-19 at 21 days after the first dose. Secondary outcomes included antibody levels, neutralizing antibody titers, and T-cell immunity. Adverse events were documented.
Summary of Main Findings
From 15 to 21 days following the first dose, the vaccine efficacy was 73.6%. At 21 days following the first dose, vaccine efficacy was 91.6%. There was no decrease in efficacy among participants over 60 years old. There were also no cases of severe confirmed COVID-19 in the vaccine group at least 21 days after the first dose. Antibody levels were measured at day 42 after the first dose. There was a statistically significant difference in antibody levels between participants aged 18-30 years and all other age groups. Neutralizing antibody levels were also measured at day 42 and no significant differences were noted based on age or sex of the participants. The most common adverse events were flu-like illness, headache, injection site reactions, and lethargy. No vaccine-related serious adverse events were noted.
This study included a separate analysis of elderly populations, which is important as this is a high risk population in which immune responses are often decreased compared to younger populations.
This is an interim analysis. Full reporting of phase 3 data will be needed to fully understand the efficacy of this vaccine. No efficacy data were reported following the booster dose, though these data should be forthcoming. Antibody levels are not compared to convalescent plasma and so the meaning of the levels detected is difficult to interpret. The full adverse event report is not included, but should be forthcoming. The study population was also not ethnically diverse, and it is not clear that further studies are planned in more diverse populations. While participants 60 years and older were included, these were small numbers (1,611 in the vaccine group and 533 in the placebo group). Further studies may be necessary to fully understand the vaccine effects in this population. The authors state that storage is approved at 2-8C. However, it was designed to be stored at -18C, and no data supporting a new storage protocol are provided. Duration of protection is unclear, but this will be analyzed further as the trial continues.
This study demonstrates that the Gam-COVID-Vac was well tolerated and highly efficacious. While this trial was set up to study a prime-boost regime, the data suggest a single dose could be sufficient. Trials to study this directly are underway.
This review was posted on: 5 February 2021