A Phase 2/3, Observer-Blind, Randomised, Controlled Study to Assess the Safety and Immunogenicity of SII-ChAdOx1 nCOV-19 (COVID-19 Vaccine) in Adults in India

Background: ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at Serum Institute of India Pvt Ltd (SIIPL) after technology transfer from AstraZeneca, was evaluated in this phase 2/3 immunobridging study. Methods: This observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). Two doses of vaccine (5 × 10¹⁰ viral particles) or placebo were given at 4-week intervals (+2-week window). Primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibodies 28 days after second dose (defined as lower 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. Anti-spike IgG response was assessed using a validated multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Findings: Between August 25 and October 31, 2020, n=1601 participants were enrolled: n=401 to the immunogenicity/reactogenicity cohort and n=1200 to the safety cohort. After two doses of SII-ChAdOx1 nCoV-19 or AZD1222, seroconversion rates for anti-spike IgG antibodies were 98·0% and 98·9%, respectively, with anti-spike IgG GMTs of 30 245·6 AU/mL (95% CI 26 794·0–34 141·8) and 28 558·3 AU/mL (23 479·3–34 735·8); SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·79–1·23). SAEs were reported in 15/1200 (1·3%, 95% CI 0·7–2·1), 2/300 (0·7%, 0·1–2·4) and 2/100 (2·0%, 0·2–7·0) participants who received SII-ChAdOx1 nCoV-19, placebo and AZD1222, respectively; none were causally related.  SARS-CoV-2 infections were observed in 1·9% (n=22), 3·4% (n=10) and 2·0% (n=2) of the SII-ChAdOx1 nCoV-19, placebo and AZD1222 groups, respectively; none were severe. Interpretation: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Trial Registration: This study was registered with number CTRI/2020/08/027170 Funding: SIIPL, Indian Council of Medical Research, AstraZeneca. Declaration of Interest: PSK, CB, AD, MG, US, DK, and BG are employees of SIIPL. JV and EJK are employees of AstraZeneca. All other authors declare no competing interests. Ethical Approval: The study was approved by the Drugs Controller General of India (DCGI) and the ethics committees of each study site.