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

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dc.contributor.authorVan der Meeren, Olivieren_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorNduba, Videlisen_ZA
dc.contributor.authorWilkinson, Robert J.en_ZA
dc.contributor.authorMuyoyeta, Mondeen_ZA
dc.contributor.authorVan Brakel, Elanaen_ZA
dc.contributor.authorAyles, Helen M.en_ZA
dc.contributor.authorHenostroza, Germanen_ZA
dc.contributor.authorThienemann, Friedrichen_ZA
dc.contributor.authorScriba, Thomas J.en_ZA
dc.contributor.authorDiacon, Andreasen_ZA
dc.contributor.authorBlatner, Gretta L.en_ZA
dc.contributor.authorDemoitie, Marie-Angeen_ZA
dc.contributor.authorTameris, Micheleen_ZA
dc.contributor.authorMalahleha, Mookhoen_ZA
dc.contributor.authorInnes, James C.en_ZA
dc.contributor.authorHellstrom, Elizabethen_ZA
dc.contributor.authorMartinson, Neilen_ZA
dc.contributor.authorSingh, Tinaen_ZA
dc.contributor.authorAkite, Elaine J.en_ZA
dc.contributor.authorKhatoon Azam, Aishaen_ZA
dc.contributor.authorBollaerts, Anneen_ZA
dc.contributor.authorGinsberg, Ann M.en_ZA
dc.contributor.authorEvans, Thomas G.en_ZA
dc.contributor.authorGillard, Paulen_ZA
dc.contributor.authorTait, Dereck R.en_ZA
dc.date.accessioned2019-10-14T14:29:40Z
dc.date.available2019-10-14T14:29:40Z
dc.date.issued2018-10-25
dc.descriptionCITATION: Van der Meeren, O. et al. 2018. Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. New England Journal of Medicine, 379:1621-1634, doi:10.1056/NEJMoa1803484.
dc.descriptionThe original publication is available at https://www.nejm.org
dc.description.abstractBACKGROUND: 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; ClinicalTrials.gov number, NCT01755598. opens in new tab.)en_ZA
dc.description.urihttps://www.nejm.org/doi/full/10.1056/NEJMoa1803484
dc.description.versionPublisher's version
dc.format.extent14 pages
dc.identifier.citationVan der Meeren, O. et al. 2018. Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. New England Journal of Medicine, 379:1621-1634, doi:10.1056/NEJMoa1803484.
dc.identifier.issn1533-4406 (online)
dc.identifier.otherdoi:10.1056/NEJMoa1803484
dc.identifier.urihttp://hdl.handle.net/10019.1/106640
dc.language.isoen_ZAen_ZA
dc.publisherMassachusetts Medical Society
dc.rights.holderMassachusetts Medical Society
dc.subjectTuberculosisen_ZA
dc.subjectTuberculosis vaccinesen_ZA
dc.titlePhase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosisen_ZA
dc.typeArticleen_ZA
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