PMID- 35501178 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20221221 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 40 IP - 24 DP - 2022 May 26 TI - Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial. PG - 3380-3388 LID - S0264-410X(22)00463-7 [pii] LID - 10.1016/j.vaccine.2022.04.035 [doi] AB - BACKGROUND: We evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants. METHODS: This phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged >/= 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or >/= 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 mug SARS-CoV-2 rS; 50 mug Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021). RESULTS: Between 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49). CONCLUSION: Two doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. FUNDING: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). CLINICALTRIALS: gov identifier: NCT04712110. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Masuda, Taisei AU - Masuda T AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: taisei.masuda@takeda.com. FAU - Murakami, Kyoko AU - Murakami K AD - Japan Medical and Policy Affairs, Medical Affairs Office, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: kyoko.murakami@takeda.com. FAU - Sugiura, Kenkichi AU - Sugiura K AD - Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: kenkichi.sugiura@takeda.com. FAU - Sakui, Sho AU - Sakui S AD - Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: sho.sakui@takeda.com. FAU - Schuring, Ron P AU - Schuring RP AD - Clinical Development, Global Vaccine Business Unit, Takeda Pharmaceuticals International AG, Switzerland. Electronic address: ron.schuring@takeda.com. FAU - Mori, Mitsuhiro AU - Mori M AD - Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: mitsuhiro.mori@takeda.com. LA - eng SI - ClinicalTrials.gov/NCT04712110 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220429 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 2SCD8Q63PF (NVX-CoV2373 adjuvated lipid nanoparticle) SB - IM MH - Adult MH - Antibodies, Viral MH - *COVID-19/prevention & control MH - *COVID-19 Vaccines/adverse effects MH - Double-Blind Method MH - Humans MH - Immunogenicity, Vaccine MH - Japan MH - SARS-CoV-2 PMC - PMC9053833 OTO - NOTNLM OT - COVID-19 OT - Immunogenicity OT - Japanese adults OT - NVX-CoV2373 OT - SARS-CoV-2 OT - Safety COIS- Declaration of competing interest TM, KM, KS, SS, and MM are employees of Takeda Pharmaceutical Company Ltd. RPS is an employee of Takeda Pharmaceuticals International AG. KM holds stocks in Takeda Pharmaceutical Company Ltd. EDAT- 2022/05/03 06:00 MHDA- 2022/05/20 06:00 PMCR- 2022/04/29 CRDT- 2022/05/02 22:03 PHST- 2022/01/21 00:00 [received] PHST- 2022/03/08 00:00 [revised] PHST- 2022/04/09 00:00 [accepted] PHST- 2022/05/03 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2022/05/02 22:03 [entrez] PHST- 2022/04/29 00:00 [pmc-release] AID - S0264-410X(22)00463-7 [pii] AID - 10.1016/j.vaccine.2022.04.035 [doi] PST - ppublish SO - Vaccine. 2022 May 26;40(24):3380-3388. doi: 10.1016/j.vaccine.2022.04.035. Epub 2022 Apr 29.