A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report.

Autor: Masuda T; Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: taisei.masuda@takeda.com., Murakami K; Japan Medical and Policy Affairs, Medical Affairs Office, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: kyoko.murakami@takeda.com., Sugiura K; Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: kenkichi.sugiura@takeda.com., Sakui S; Statistical and Quantitative Sciences, Data Sciences Institute, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: sho.sakui@takeda.com., Philip Schuring R; Clinical Development, Global Vaccine Business Unit, Takeda Pharmaceutical International Ag, Switzerland. Electronic address: ron.schuring@takeda.com., Mori M; Japan Development, Global Vaccine Business Unit, Takeda Pharmaceutical Company Ltd, Japan. Electronic address: mitsuhiro.mori@takeda.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2022 Mar 18; Vol. 40 (13), pp. 2044-2052. Date of Electronic Publication: 2022 Feb 08.
DOI: 10.1016/j.vaccine.2022.02.030
Abstrakt: 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 μg 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 μg 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.
Competing Interests: 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.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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