A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years

Background A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods This was a Phase 2/3 observer-blind, randomized, controlled immuno-bridging study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The lower bound of 95% CI of GMT ratios for anti-S IgG GMEUs and neutralizing antibodies in both age groups to those observed in Indian adults were >0.67, thus non-inferiority was met [Anti-S IgG GMT ratios 1.52 (1.38, 1.67), 1.20 (1.08, 1.34) and neutralizing antibodies GMT ratios 1.93 (1.70, 2.18), 1.33 (1.17, 1.50) for 2 to 11 years and 12 to 17 years groups, respectively]. The seroconversion rate was ≥ 98% (anti-S IgG) and ≥ 97.9 % (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, were the common (≥5%) solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults. Registration - CTRI No. CTRI/2021/02/031554 ### Competing Interest Statement CSP is Chairman and Managing Director of SIIPL. PSK, BG, DK and US are employed by Serum Institute of India Pvt. Ltd., which is the manufacturer of the study vaccine. JSP, MZ, SCC, RM, FD, GMG are employees of Novavax Inc. MP and SH are employees of 360biolabs All other authors declare no competing interests. ### Clinical Trial CTRI No.: CTRI/2021/02/031554 ### Clinical Protocols ### Funding Statement The study was funded by Serum Institute of India Pvt. Ltd. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Indian regulatory authorities and Institutional Ethics Committees of each of 10 participating study sites - Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India, KEM Hospital Research Centre, Pune, Maharashtra, India, Hamdard Institute of Medical Sciences and Research with Centre for health Research and Development (CHRD), New Delhi, India, Bharati Vidyapeeth Deemed University Medical College and Hospital, Pune, Maharashtra, India, Super Speciality Hospital, Government Medical College and Hospital, Nagpur, Maharashtra, India, Sushila Nayar School of Public Health, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India, JSS Academy of Higher Education and Research, Mysore, Karnataka, India, Christian Medical College & Hospital, Ludhiana, Punjab, India, TN Medical College & BYL Nair Hospital, Mumbai, Maharashtra, India, Post Graduate Institute of Medical Education and Research, Chandigarh, India I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.