Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

Abstract

Introduction The 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. Methods This 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. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (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 1090 participants was 72 (50, 116) EU/mL. Discussion The 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 registration ClinicalTrials.gov NCT02876328. Registered on 23 August 2016.

Immune response of a two-dose heterologous Ebola vaccine regimen: summary of three African clinical trials using a single validated Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay in a single accredited laboratory

“…EBL2004/PREVAC was a randomised, double-blind, placebo-controlled, phase 2 trial ( NCT02876328 ) conducted at six sites in Guinea, Liberia, Mali, and Sierra Leone. 12 , 15 Healthy individuals aged ≥1 year were eligible to participate and were randomised to one of five study arms. Enrolment began on 16 April 2018 and the last visits for immunogenicity occurred on 25 November 2019 for adults and 12 December 2019 for paediatric participants.…”

Prevalence of malaria and helminth infections in rural communities in northern Sierra Leone, a baseline study to inform Ebola vaccine study protocols

“…This trial is investigating the initial and long-term safety and immunogenicity of the two prophylactic Ebola vaccines, the two-dose heterologous vaccine regimen of Ad26.ZEBOV and MVA-BN-Filo vaccines (Janssen Vaccines & Prevention B.V.) and a single or boosted regimen of the recombinant Vesicular Stomatitis Virus (rVSV) vaccine (Merck Sharp and Dohme) ( https://clinicaltrials.gov/ct2/show/NCT02876328 ) [ 3 ]. Initial studies of the vaccine regimens have demonstrated the safety and immunogenicity of each vaccine [ 3 – 5 ]. The rVSV vaccine has shown protection against Ebola disease using ring vaccination in Guinea and the Democratic Republic of Congo (DRC) [ 6 , 7 ].…”

Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults

“…The Partnership for Research on Ebola VACcination (PREVAC) is a phase 2, randomized, controlled trial of 2 leading Ebola vaccines and 3 vaccination strategies (Ad26.ZEBOV/MVABN-Filo, 1-dose rVSVΔG-ZEBOV-GP, and 2-dose rVSVΔG-ZEBOV-GP) in children ≥1 year of age and adults [ 11 ]. Primary results [ 12 ] demonstrated that a single dose of rVSVΔG-ZEBOV-GP elicited robust binding antibody responses in children and adults by Day 14 that were sustained through Month 12 and no safety concerns were identified in children receiving 1 or 2 doses of rVSVΔG-ZEBOV-GP.…”