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

Vaccine. 2022 Mar 18;40(13):2044-2052. doi: 10.1016/j.vaccine.2022.02.030. Epub 2022 Feb 8.

Abstract

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.

Keywords: COVID-19; Immunogenicity; SARS-CoV-2; Safety; Vaccine; mRNA-1273.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273*
  • Adult
  • Aged
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / prevention & control
  • Double-Blind Method
  • Humans
  • Immunogenicity, Vaccine
  • Japan
  • SARS-CoV-2
  • Vaccines, Synthetic
  • Young Adult
  • mRNA Vaccines

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines
  • 2019-nCoV Vaccine mRNA-1273

Associated data

  • ClinicalTrials.gov/NCT04677660