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

Taisei Masuda, Kyoko Murakami, Kenkichi Sugiura, Sho Sakui, Ron Philip Schuring, Mitsuhiro Mori, Taisei Masuda, Kyoko Murakami, Kenkichi Sugiura, Sho Sakui, Ron Philip Schuring, Mitsuhiro Mori

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.

Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Schematic of trial design. COVID-19 = coronavirus disease 2019, N/n = number of participants.
Fig. 2
Fig. 2
Participant disposition.
Fig. 3
Fig. 3
Local and systemic solicited adverse events within 7 days after injections in A) all age groups and B) by age group. AE = adverse event.
Fig. 3
Fig. 3
Local and systemic solicited adverse events within 7 days after injections in A) all age groups and B) by age group. AE = adverse event.

References

    1. Ali K., Berman G., Zhou H., Deng W., Faughnan V., Coronado-Voges M., et al. Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents. N Engl J Med. 2021;385(24):2241–2251.
    1. Anderson E.J., Rouphael N.G., Widge A.T., Jackson L.A., Roberts P.C., Makhene M., et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383(25):2427–2438.
    1. Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416.
    1. Chu L., McPhee R., Huang W., Bennett H., Pajon R., Nestorova B., et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. Vaccine. 2021;39(20):2791–2799.
    1. Corbett K.S., Flynn B., Foulds K.E., Francica J.R., Boyoglu-Barnum S., Werner A.P., et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N Engl J Med. 2020;383(16):1544–1555.
    1. Jackson L.A., Anderson E.J., Rouphael N.G., Roberts P.C., Makhene M., Coler R.N., et al. An mRNA vaccine against SARS-CoV-2 - preliminary report. N Engl J Med. 2020;383(20):1920–1931.
    1. Mahase E. Covid-19: UK approves Moderna vaccine to be given as two doses 28 days apart. BMJ. 2021;372:n74.
    1. Iguacel I., Maldonado A.L., Ruiz-Cabello A.L., Casaus M., Moreno L.A., Martínez-Jarreta B. Association between COVID-19 vaccine side effects and body mass index in Spain. Vaccines (Basel) 2021;9(11):1321. doi: 10.3390/vaccines9111321.
    1. Blumenthal K.G., Freeman E.E., Saff R.R., Robinson L.B., Wolfson A.R., Foreman R.K., et al. Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2. N Engl J Med. 2021;384(13):1273–1277.
    1. Kelso J.M., Greenhawt M.J., Li J.T., Nicklas R.A., Bernstein D.I., Blessing-Moore J., et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy Clin Immunol. 2012;130(1):25–43.
    1. Chung H., He S., Nasreen S., Sundaram M.E., Buchan S.A., Wilson S.E., et al. Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study. BMJ. 2021;374:n1943.
    1. Chemaitelly H., Yassine H.M., Benslimane F.M., Al Khatib H.A., Tang P., Hasan M.R., et al. mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar. Nat Med. 2021;27(9):1614–1621.
    1. 02 September 2020.
    1. September 2007.
    1. December 17, 2020.

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