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.
Bibliographical noteFunding Information:
Funding was provided in part by NIAID under NCI contract HHSN261201500003I through the Frederick National Laboratory for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
This research was supported in part by the National Institutes of Health (NIH) and by Institut national de la santé et de la recherche médicale (Inserm) and by the London School of Hygiene and Tropical Medicine (LSHTM).
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115854. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. The dissemination represents only the authors’ views and IMI2JU is not responsible for any use of the information contained in the dissemination.
This project has received funding by a dedicated Inserm allocation on behalf the French Research Ministry.
We are grateful to the Ministries of Health of Guinea, Liberia, Sierra Leone, and Mali who permitted the conduct of the trial. We furthermore thank Alima and all site collaborators for their contribution in the implementation of the trial. The authors and study team wish to thank the many participants who contributed to the trial.
© 2021, The Author(s).
- Clinical trials
- Randomized controlled trials