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. 2023 Mar:10:100139.
doi: 10.1016/j.lansea.2022.100139. Epub 2023 Jan 11.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study

Prasad S Kulkarni  1 , Abhijit Kadam  2 , Sheela Godbole  2 , Varsha Bhatt  3 , Abhishek Raut  4 , Sunil Kohli  5 , Santanu Tripathi  6 , Praveen Kulkarni  7 , Rakhi Ludam  8 , Madhav Prabhu  9 , Ashish Bavdekar  10 , Nithya J Gogtay  11 , Sushant Meshram  12 , Tamilarasu Kadhiravan  13 , Sonali Kar  14 , D H Ashwath Narayana  15 , Clarence Samuel  16 , Govind Kulkarni  17 , Abhay Gaidhane  18 , Dipu Sathyapalan  19 , Sidram Raut  20 , Vijay Hadda  21 , Hira Lal Bhalla  22 , Chetanraj Bhamare  1 , Abhijeet Dharmadhikari  1 , Joyce S Plested  23 , Shane Cloney-Clarke  23 , Mingzhu Zhu  23 , Melinda Pryor  24 , Stephanie Hamilton  24 , Madhuri Thakar  2 , Ashwini Shete  2 , Manish Gautam  1 , Nivedita Gupta  25 , Samiran Panda  25 , Umesh Shaligram  1 , Cyrus S Poonawalla  1 , Balram Bhargava  25 , Bhagwat Gunale  1 , Dhananjay Kapse  1 ; COVOVAX Study Group
Collaborators, Affiliations

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study

Prasad S Kulkarni et al. Lancet Reg Health Southeast Asia. 2023 Mar.

Abstract

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study.

Methods: This was an observer-blind, randomised, phase 2/3 study 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 (940 safety cohort and 460 immunogenicity 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-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) 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 at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554.

Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. 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 day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported.

Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile.

Funding: SIIPL, Indian Council of Medical Research, Novavax.

Keywords: Immunogenicity; NVX-CoV2373; Non-inferiority; SII-NVX-CoV2373; Safety.

PubMed Disclaimer

Conflict of interest statement

PSK, DK, BG, CB, AD, MG, and US are employees of SIIPL. JSP, MZ and SCC are employees of Novavax Inc. CSP is Chairman and Managing Director of SIIPL. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT Flow Chart – Phase 2. ∗Due to temperature excursion reported at the site, 3 participants could not be vaccinated and by then target of 200 participants was completed at other study sites.
Fig. 2
Fig. 2
CONSORT Flow Chart – Phase 3. ∗Of total 1431 screened, 32 were screen failures with 1 screen failure inadvertently entered as randomized in the database. Thus, actually 1399 were randomized and 1 screen failure was inadvertently randomized.
Fig. 3
Fig. 3
Line plots of GMEU (including 95% CIs) of Anti-S IgG - Immunogenicity Analysis Population.
Fig. 4
Fig. 4
Line plots of GMT (including 95% CIs) of Neutralizing antibodies (nAb) against SARS-Cov-2 - Immunogenicity Analysis Population.
See this image and copyright information in PMC

References

    1. Priyanka Choudhary OP. Singh I, Patra G. Aerosol transmission of SARS-CoV-2: the unresolved paradox. Travel Med Infect Dis. 2020;37:101869. - PMC - PubMed
    1. World Health Organization (WHO) WHO Director-General’s opening remarks at the media briefing on COVID-19. 2020. https://www.who.int/director-general/speeches/detail/who-director-genera...
    1. 2022. https://www.mygov.in/covid-19
    1. Keech C., Albert G., Cho I., et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. 2020 Dec 10;383(24):2320–2332. - PMC - PubMed
    1. Formica N., Mallory R., Albert G., et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: a phase 2 randomized placebo-controlled trial. PLoS Med. 2021 Oct 1;18(10):e1003769. - PMC - PubMed