PMID- 37523166 OWN - NLM STAT- Publisher LR - 20231102 IS - 2168-6211 (Electronic) IS - 2168-6203 (Print) IS - 2168-6203 (Linking) VI - 177 IP - 9 DP - 2023 Jul 31 TI - Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial. PG - 911-20 LID - 10.1001/jamapediatrics.2023.2552 [doi] AB - IMPORTANCE: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown. OBJECTIVE: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo. DESIGN, SETTING, AND PARTICIPANTS: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022. Participants were randomized 3:1 to SII-NVX-CoV2373 or placebo and monitored for 179 days. The participants, study team, and laboratory staff were blinded. This was a multicenter study conducted across 10 tertiary care hospitals in India. Exclusion criteria included previous COVID-19 infection or vaccination, immunocompromised condition, and immunosuppressive medications. INTERVENTIONS: Two doses of 0.5-mL SII-NVX-CoV2373 or placebo were administered intramuscularly on days 1 and 22. MAIN OUTCOMES AND MEASURES: Primary outcomes were geometric mean titer ratio of both anti-spike (anti-S) IgG and neutralizing antibodies (NAbs) between both pediatric age groups to that of adults on day 36. Noninferiority was concluded if the lower bound of 95% CI of this ratio was greater than 0.67 for each age group. Both the antibodies were assessed for the index strain and for selected variants at various time points. Solicited adverse events (AEs) were recorded for 7 days after each vaccination, unsolicited AEs were recorded for 35 days, and serious AEs and AEs of special interest were recorded for 179 days. RESULTS: A total of 460 children in each age cohort were randomized to receive vaccine or placebo. The mean (SD) age was 6.7 (2.7) years in the child cohort and 14.3 (1.6) years in the adolescent cohort; 231 participants (50.2%) in the child cohort and 218 in the adolescent cohort (47.4%) were female. Both anti-S IgG and NAb titers were markedly higher in the SII-NVX-CoV2373 group than in the placebo group on both day 36 and day 180. The geometric mean titer ratios compared to those in adults were 1.20 (95% CI, 1.08-1.34) and 1.52 (95% CI, 1.38-1.67) for anti-S IgG in adolescents and children, respectively; while for NAbs, they were 1.33 (95% CI, 1.17-1.50) and 1.93 (95% CI, 1.70-2.18) in adolescents and children, respectively, indicating noninferiority. SII-NVX-CoV2373 also showed immune responses against variants studied. Injection site reactions, fever, headache, malaise, and fatigue were common solicited AEs. There were no AEs of special interest and no causally related serious AEs. CONCLUSIONS AND RELEVANCE: SII-NVX-CoV2373 was safe and well tolerated in children and adolescents in this study. The vaccine was highly immunogenic and may be used in pediatric vaccination against COVID-19. TRIAL REGISTRATION: Clinical Trials Registry of India Identifier: CTRI/2021/02/031554. FAU - Gunale, Bhagwat AU - Gunale B AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Kapse, Dhananjay AU - Kapse D AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Kar, Sonali AU - Kar S AD - Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India. FAU - Bavdekar, Ashish AU - Bavdekar A AD - King Edward Memorial Hospital Research Centre, Pune, Maharashtra, India. FAU - Kohli, Sunil AU - Kohli S AD - Hamdard Institute of Medical Sciences and Research With Centre for Health Research and Development, New Delhi, India. FAU - Lalwani, Sanjay AU - Lalwani S AD - Bharati Vidyapeeth Deemed University Medical College and Hospital, Pune, Maharashtra, India. FAU - Meshram, Sushant AU - Meshram S AD - Super Speciality Hospital, Government Medical College and Hospital, Nagpur, Maharashtra, India. FAU - Raut, Abhishek AU - Raut A AD - Sushila Nayar School of Public Health, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India. FAU - Kulkarni, Praveen AU - Kulkarni P AD - JSS Academy of Higher Education and Research, Mysore, Karnataka, India. FAU - Samuel, Clarence AU - Samuel C AD - Christian Medical College & Hospital, Ludhiana, Punjab, India. FAU - Munshi, Renuka AU - Munshi R AD - Topiwala National Medical College and Bai Yamunabai Laxman Nair Hospital, Mumbai, Maharashtra, India. FAU - Gupta, Madhu AU - Gupta M AD - Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Plested, Joyce S AU - Plested JS AD - Novavax, Gaithersburg, Maryland. FAU - Cloney-Clark, Shane AU - Cloney-Clark S AD - Novavax, Gaithersburg, Maryland. FAU - Zhu, MingZhu AU - Zhu M AD - Novavax, Gaithersburg, Maryland. FAU - Pryor, Melinda AU - Pryor M AD - 360biolabs, Melbourne, Victoria, Australia. FAU - Hamilton, Stephanie AU - Hamilton S AD - 360biolabs, Melbourne, Victoria, Australia. FAU - Thakar, Madhuri AU - Thakar M AD - Indian Council of Medical Research, National AIDS Research Institute, Pune, Maharashtra, India. FAU - Shete, Ashwini AU - Shete A AD - Indian Council of Medical Research, National AIDS Research Institute, Pune, Maharashtra, India. FAU - Dharmadhikari, Abhijeet AU - Dharmadhikari A AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Bhamare, Chetanraj AU - Bhamare C AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Shaligram, Umesh AU - Shaligram U AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Poonawalla, Cyrus S AU - Poonawalla CS AD - Serum Institute of India, Pune, Maharashtra, India. FAU - Mallory, Raburn M AU - Mallory RM AD - Novavax, Gaithersburg, Maryland. FAU - Glenn, Gregory M AU - Glenn GM AD - Novavax, Gaithersburg, Maryland. FAU - Kulkarni, Prasad S AU - Kulkarni PS AD - Serum Institute of India, Pune, Maharashtra, India. CN - COVOVAX-Ped study group LA - eng PT - Journal Article DEP - 20230731 PL - United States TA - JAMA Pediatr JT - JAMA pediatrics JID - 101589544 SB - IM PMC - PMC10391359 COIS- Conflict of Interest Disclosures: Drs Gunale, Kapse, Bhamare, Shaligram, P. S. Kulkarni, and Mr Dharmadhikari are employed by Serum Institute of India, which funded the present study and manufacture the study vaccine, during the conduct of the study and outside the submitted work. Drs Plested and Zhu and Ms Cloney-Clark reported employment and stock holdings at Novavax during the conduct of the study. Dr Pryor reported a contract between Serum Institute of India and 360biolabs during the conduct of the study. Dr Hamilton reported payment from Serum Institute of India through a contract with 360biolabs to complete testing during the conduct of the study; additionally, 360biolabs received financial compensation from Novavax for contracted work outside the submitted work. Dr Poonawalla is chairman and managing director of Serum Institute of India, which funded this study and manufactured the study vaccine, during the conduct of the study and outside the submitted work. Dr Mallory reports employment and stock holdings at Novavax during the conduct of the study. Dr Glenn reported personal fees from Novavax during the conduct of the study and outside the submitted work; in addition, Dr Glenn had a patent pending for Novavax and is employed by Novavax. No other disclosures were reported. FIR - Samantaray, Pramod C IR - Samantaray PC FIR - Kawade, Anand IR - Kawade A FIR - Gondhali, Arunkumar IR - Gondhali A FIR - Jain, Vineet IR - Jain V FIR - Goyal, Nidhi IR - Goyal N FIR - Arya, Alok IR - Arya A FIR - Rongsen-Chandola, Temsunaro IR - Rongsen-Chandola T FIR - Palkar, Sonali IR - Palkar S FIR - Hanumante, Neeta M IR - Hanumante NM FIR - Bhatnagar, Manoj H IR - Bhatnagar MH FIR - Shyamkuwar, Chetna A IR - Shyamkuwar CA FIR - Garg, B S IR - Garg BS FIR - Meshram, Payal IR - Meshram P FIR - Deotale, Vijayshri IR - Deotale V FIR - Mahajan, Kamlesh IR - Mahajan K FIR - Kalantri, Ashwini IR - Kalantri A FIR - V, Prajwala H IR - V PH FIR - Rao, Vijayalakshmi V IR - Rao VV FIR - Kamra, Deepshikha IR - Kamra D FIR - Singh, Aradhana IR - Singh A FIR - Kumbhar, Dipti IR - Kumbhar D FIR - Shafiq, Nusrat IR - Shafiq N FIR - Sharma, Indrakshi IR - Sharma I FIR - Choche, Rahul IR - Choche R FIR - Ghatage, Deepak IR - Ghatage D FIR - Salvi, Sugam IR - Salvi S EDAT- 2023/07/31 13:10 MHDA- 2023/07/31 13:10 PMCR- 2024/07/31 CRDT- 2023/07/31 11:33 PHST- 2024/07/31 00:00 [pmc-release] PHST- 2023/07/31 13:10 [medline] PHST- 2023/07/31 13:10 [pubmed] PHST- 2023/07/31 11:33 [entrez] AID - 2807909 [pii] AID - poi230043 [pii] AID - 10.1001/jamapediatrics.2023.2552 [doi] PST - aheadofprint SO - JAMA Pediatr. 2023 Jul 31;177(9):911-20. doi: 10.1001/jamapediatrics.2023.2552.