PMID- 35177302 OWN - NLM STAT- MEDLINE DCOM- 20220317 LR - 20231213 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 40 IP - 13 DP - 2022 Mar 18 TI - A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report. PG - 2044-2052 LID - S0264-410X(22)00164-5 [pii] LID - 10.1016/j.vaccine.2022.02.030 [doi] AB - INTRODUCTION: The mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants. METHODS: This phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged >/= 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/>/= 65 years) and randomised to receive two doses of 100 mug mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response. RESULTS: Participants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; >/= 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; >/= 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49). CONCLUSION: Two doses of 100 mug mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged >/= 20 years. FUNDING: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). CLINICALTRIALS: gov: NCT04677660. 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 - Philip Schuring, Ron AU - Philip Schuring R AD - Clinical Development, Global Vaccine Business Unit, Takeda Pharmaceutical 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/NCT04677660 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 - 20220208 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (Vaccines, Synthetic) RN - 0 (mRNA Vaccines) RN - EPK39PL4R4 (2019-nCoV Vaccine mRNA-1273) SB - IM MH - *2019-nCoV Vaccine mRNA-1273 MH - Adult MH - Aged MH - Antibodies, Neutralizing 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 MH - Vaccines, Synthetic MH - Young Adult MH - mRNA Vaccines PMC - PMC8824367 OTO - NOTNLM OT - COVID-19 OT - Immunogenicity OT - SARS-CoV-2 OT - Safety OT - Vaccine OT - mRNA-1273 COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employees of Takeda Pharmaceutical Company Ltd with the exception of RS, who is an employee of Takeda Pharmaceutical International Ag. EDAT- 2022/02/19 06:00 MHDA- 2022/03/18 06:00 PMCR- 2022/02/08 CRDT- 2022/02/18 05:35 PHST- 2021/11/12 00:00 [received] PHST- 2022/01/17 00:00 [revised] PHST- 2022/02/04 00:00 [accepted] PHST- 2022/02/19 06:00 [pubmed] PHST- 2022/03/18 06:00 [medline] PHST- 2022/02/18 05:35 [entrez] PHST- 2022/02/08 00:00 [pmc-release] AID - S0264-410X(22)00164-5 [pii] AID - 10.1016/j.vaccine.2022.02.030 [doi] PST - ppublish SO - Vaccine. 2022 Mar 18;40(13):2044-2052. doi: 10.1016/j.vaccine.2022.02.030. Epub 2022 Feb 8.