Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

New England Journal of Medicine
October 12, 2017  Vol. 377 No. 15
http://www.nejm.org/toc/nejm/medical-journal

Original Article
Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia
Stephen B. Kennedy, M.D., Fatorma Bolay, Ph.D., Mark Kieh, M.D., Greg Grandits, M.S., Moses Badio, M.Sc., Ripley Ballou, M.D., Risa Eckes, B.S.N., Mark Feinberg, M.D., Ph.D., Dean Follmann, Ph.D., Birgit Grund, Ph.D., Swati Gupta, Dr.P.H., Lisa Hensley, Ph.D., Elizabeth Higgs, M.D., Krisztina Janosko, B.S., Melvin Johnson, B.Sc., Francis Kateh, M.D., James Logue, M.S., Jonathan Marchand, M.S., Thomas Monath, M.D., Martha Nason, Ph.D., Tolbert Nyenswah, M.P.H., François Roman, Ph.D., Eric Stavale, M.S., Julian Wolfson, Ph.D., James D. Neaton, Ph.D., and H. Clifford Lane, M.D., for the PREVAIL I Study Group*
N Engl J Med 2017; 377:1438-1447 October 12, 2017 DOI: 10.1056/NEJMoa1614067
Abstract
Background
The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia.
Full Text of Background…
Methods
We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated.
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Results
A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons).
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Conclusions
A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407.)