Heterologous recombinant adenovirus-based COVID-19 vaccine (Gam-COVID-Vac) is tolerable and highly efficacious

1. Efficacy of the Gam-COVID-Vac (Sputnik V) vaccine against COVID-19 was 91.6%.

2. In the vaccine group, there were no confirmed cases of moderate or severe COVID-19 21 days after the first dose.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Global efforts to develop safe and effective vaccines for COVID-19 prevention are ongoing. In Russia, a combined vector vaccine was developed based on replication-deficient adenovirus type 26 (rAd26) and type 5 (rAd5) to trigger a durable and long-lasting immune response. During phase 1/2  clinical trials, this vaccine was well tolerated and highly immunogenic in healthy participants, allowing it to be provisionally approved for use in high-risk populations. This study aimed to evaluate phase 3 efficacy and safety results of Gam-COVID-Vac (Sputnik V) in adults, with subanalysis of adults older than 60 years. Primary endpoint was the proportion of participants with PCR-confirmed COVID-19 at 21 days after the first dose, while secondary endpoints included severity of COVID-19, changes in SARS-CoV-2 antibody levels, and incidence and severity of adverse events. According to study results, fewer patients in the vaccine group were confirmed to have COVID-19 compared to control. There were no confirmed cases of moderate or severe COVID-19 in the vaccine group 21 days after receiving the first dose. The proportion of patients with serious adverse events was similar in both groups, although none were due to vaccination. A major weakness of this study was that patients were asked to self-report symptoms of COVID-19, which was confirmed by PCR testing. It is likely that asymptomatic causes of COVID-19 were excluded from the analysis. Nevertheless, this study sheds light onto the high efficacy, immunogenicity, and tolerability profile of Gam-COVID-Vac in Russia.

Click to read the study in The Lancet

Relevant Reading: Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

In-depth [randomized controlled trial]: Between Sept 7 and Nov 24, 2020, 21 977 patients were enrolled across 25 hospitals and polyclinics in Moscow, Russia. Included patients were those aged 18 and older, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the last 14 days, and no vaccinations 30 days before enrolment. Those that did not meet the eligibility criteria or missed the second dose were excluded. Altogether, 19 866 patients (14 964 in the vaccine group and 4902 in the placebo group) were included in analysis. Among enrolled patients, the mean age was 45.3 years (standard deviation [SD] 12.0) in the vaccine group and 45.3 years (SD 11.9) in the placebo group.

The primary endpoint concerning PCR-confirmed COVID-19 21 days after the first vaccine dose was substantially greater in the placebo group (62 of 4902, 1.3%) than in the vaccine group (16 of 14 964, 0.1%). Overall efficacy of Gam-COVID-Vac was 91.6% (95% confidence interval [CI] 85.6-95.2), while observed efficacy was > 87% in all age and sex subgroups. From 15 to 21 days since the first dose, vaccine efficacy was 73.6% (p=0.048) which increased to 100% (p<0.0001) from day 21 and onwards. In the vaccine group, most of the COVID-19 cases occurred prior to administration of the second dose. There were zero (vaccine group) and twenty (placebo) confirmed cases of moderate or severe COVID-19 at least 21 days after the first dose. The majority of adverse events were grade 1 (7485 of 7966 events, 94%). The likelihood of serious adverse outcomes was similar in both groups (0.3% in the vaccine group vs. 0.4% in the placebo group); however, none were associated with vaccination. In total, four deaths were reported during the study (three in the vaccine group and one in the placebo group). Again, none of these deaths were vaccine related. Findings from this study suggest that Gam-COVID-Vac seems promising based on phase 3 trials and appears to be well tolerated in a large cohort.

Image: PD

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