Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial

Abstract

Background: We report the clinical efficacy against COVID 19 infection of BBV152, a whole virion inactivated SARS CoV 2 vaccine formulated with a Toll like receptor 7/8 agonist molecule adsorbed to alum (Algel IMDG). Methods: We did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18 to 98 years) randomised 1:1 using a sponsor-supplied randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory confirmed symptomatic COVID 19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in subgroups for age (18 to < 60 years and >=60 years) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots. Findings: Between November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0.77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77.8% (95% CI: 65.2,86.4). Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93.4% (57.1,99.8). Efficacy against asymptomatic COVID 19 was 63.6% (29.0, 82.4). BBV152 conferred 65.2% (95% CI: 33.1, 83.0) protection against the SARS CoV 2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported. Interpretation: BBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID 19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines.