Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis

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Title: Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis
Authors: Van Der Meeren, O
Hatherill, M
Nduba, V
Wilkinson, RJ
Muyoyeta, M
Van Brakel, E
Ayles, HM
Henostroza, G
Thienemann, F
Scriba, TJ
Diacon, A
Blatner, GL
Demoitié, M-A
Tameris, M
Malahleha, M
Innes, JC
Hellstrom, E
Martinson, N
Singh, T
Akite, EJ
Azam, AK
Bollaerts, A
Ginsberg, AM
Evans, TG
Gillard, P
Tait, DR
Item Type: Journal Article
Abstract: Background A vaccine to interrupt the transmission of tuberculosis is needed. Methods We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)–negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette–Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. Results We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. Conclusions M72/AS01E provided 54.0% protection for M. tuberculosis–infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; number, NCT01755598.)
Issue Date: 25-Oct-2018
Date of Acceptance: 4-Sep-2018
ISSN: 0028-4793
Publisher: Massachusetts Medical Society
Start Page: 1621
End Page: 1634
Journal / Book Title: New England Journal of Medicine
Volume: 379
Copyright Statement: © 2018 Massachusetts Medical Society. All rights reserved.
Sponsor/Funder: Wellcome Trust
European and Developing Countries Clinical Trial P
European and Developing Countries Clinical Trials Partnership
Funder's Grant Number: 104803/Z/14/ZR
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine

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