Moses Badio1, Edouard Lhomme2, Mark Kieh1, Abdoul Habib Beavogui3, Stephen B Kennedy1, Seydou Doumbia4, Bailah Leigh5, Samba O Sow6, Alpha Diallo7, Daniela Fusco7, Matthew Kirchoff8, Monique Termote2, Renaud Vatrinet9, Deborah Wentworth10, Helène Esperou7, H Clifford Lane8, Jerome Pierson8, Deborah Watson-Jones11, Céline Roy1, Eric D'Ortenzio9,12, Brian Greenwood11, Genevieve Chêne1, Laura Richert1, James D Neaton10, Yazdan Yazdanpanah13,14. 1. Partnership for Research on Ebola Virus in Liberia (PREVAIL), Monrovia, Liberia. 2. Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, F-33000, Bordeaux, France. 3. Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah, Mafèrinyah, Guinea. 4. University of Sciences, Technique and Technology of Bamako, Bamako, Mali. 5. College of Medicine and Allied Health Sciences (COMAHS), University of Sierra Leone, Freetown, Sierra Leone. 6. Centre pour le Développement des Vaccins, Bamako, Mali. 7. INSERM, Pôle de Recherche Clinique, 75013, Paris, France. 8. National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. 9. REACTing, Institut Thématique Immunologie, Inflammation, Infectiologie et Microbiologie, Inserm, Paris, France. 10. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. 11. London School of Hygiene & Tropical Medicine, London, UK. 12. AP-HP, Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, F-75018, Paris, France. 13. REACTing, Institut Thématique Immunologie, Inflammation, Infectiologie et Microbiologie, Inserm, Paris, France. yazdan.yazdanpanah@aphp.fr. 14. AP-HP, Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, F-75018, Paris, France. yazdan.yazdanpanah@aphp.fr.
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.
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.
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