Abstract
IntroductionThe Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments.MethodsThis is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection.ResultsFrom April 2017 to December 2018, a total of 5,002 volunteers were screened and 4,789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4,789 participants, 2,560 (53%) were adults and 2,229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years; 750 (16%) 5 to 11 years; and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1,090 participants was 72 (50, 116) EU/mL.DiscussionThe PREVAC trial is evaluating - placebo-controlled - two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children.Trial registrationClinicaltrials.gov, NCT02876328. Registred 23 August 2016, https://clinicaltrials.gov/ct2/show/NCT02876328
NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: Results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial
