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Safety and Immunogenicity of SII-NVX-CoV2373 (COVID-19 Vaccine) In Adults in a Phase 2/3, Observer-Blind, Randomised, Controlled Study
31 Pages Posted: 8 Jul 2022More...
Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ~90% efficacy against symptomatic COVID-19. The same vaccine is now manufactured in India at a large scale after technology transfer (called as SII- NVX-CoV2373).
Methods: This was an observer-blind; randomised study that was conducted in two phases in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (Nuvaxovid™); among them, 940 were in the safety cohort and 460 in the immunogenicity and reactogenicity cohort. Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-SARS-CoV-2 spike (anti-S) IgG antibodies 14 days after the second dose and to determine the incidence of serious adverse events (SAEs) causally related to SII-NVX-CoV2373 through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAbs) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, Day 22, Day 36 and Day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay baseline, Day 36 and Day 180. The total safety follow-up was for 6 months after the first dose. Trial registration: CTRI/2021/02/031554.
Findings: In the Phase 2 part, 200 participants received the first dose while in the Phase 3 part, 1396 participants received the first dose. After two doses, SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At 14 days after the second dose, there was more than 58 fold rise in anti-S IgG and nAb titres compared to baseline in both the groups and the seroconversion rates for anti-S IgG antibodies as well as for nAbs were more than 92% in both the groups. On day 180 visit, both anti-S IgG and nAb titers declined to levels slightly lower than those after the first dose (13 to 22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. Overall 13 SAEs were reported in 12 participants; none were causally related to study vaccines. No adverse event of special interest (AESI) was reported.
Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has an acceptable safety/reactogenicity profile.
Trial registration: CTRI/2021/02/031554
Funding SIIPL, Indian Council of Medical Research, Novavax.
Declaration of Interest: PSK, CSP, CB, AD, MG, US, DK, and BG are employees of SIIPL. JSP, MZ and SCC are employees of Novavax Inc. All other authors declare no competing interests
Ethical Approval: The study was approved by the Drugs Controller General of India (DCGI) for the Phase 2 and the Phase 3 parts sequentially. Institutional ethics committees of each of the 20 participating study sites provided the approval for the study before study initiation at the respective study sites.The study was conducted in compliance with the ICH-GCP guidelines [E6(R2)] and the principles of the Declaration of Helsinki (2013, Fortaleza), as well as the guidelines of the Indian Council of Medical Research (2017) and the New Drugs and Clinical Trial Rules (2019). Written informed consent was provided by each participant before enrolment.
Keywords: SII-NVX-CoV2373, NVX-CoV2373, safety, immunogenicity, non-inferiority
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