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
Moses Badio, Édouard Lhomme, Mark Kieh, Abdoul Habib Béavogui, Stephen B. Kennedy, Seydou Doumbia, Bailah Leigh, Samba O. Sow, Alpha Diallo, Daniela Fusco, Matthew Kirchoff, Monique Termote, Renaud Vatrinet, Deborah Wentworth, Hélène Espérou, H. Clifford Lane, Jérôme Pierson, Deborah Watson‐Jones, Céline Roy, Éric D’Ortenzio, Brian Greenwood, Geneviève Chêne, Laura Richert, James D. Neaton, Yazdan Yazdanpanah, the PREVAC study team, Abdoulaye Coulibaly, Jamilia Aboulhab, Pauline Akoo, Esther Akpa, Robert Akpata, Sara Albert, Boni Maxime Ale, Benetta C. Andrews, Stephane Anoma, Saw-San Assiandi, Augustin Augier, Ken Awuondo, Moses Badio, Aminata Bagayoko, Nyasha Bakare, Abby Balde, Lamin Molecule Bangura, Kesha Barrington, Eric Barte de Saint Fare, Beth Baseler, Ali Bauder, Claire Bauduin, Luke Bawo, Abdoul Habib Béavogui, Michael Belson, Marion Bererd, Teedoh Beyslow, Blandine Binachon, Julie Blie, Viki Bockstal, Youba Boire, Patricia Boison, Fatorma Bolay, Aliou Boly, Anne Gael Borg, Donna Bowers, Sarah Browne, Barbara Cagniard, Kelly Cahill, Aissata Abdoulaye Camara, Keira Camara, Modet Camara, Cécilia Campion, Jennifer Cash, Siew Pin Chai, Francois Chambelin, Keita Chieck, Geneviève Chêne, Séverine Ciancia, Papa Ndiaga Cissé, Elfrida Clide, Céline Colin, Beth-Ann Coller, Djélikan Siaka Conde, Katherine Cone, Laurie Connor, Nicholas E. Connor, Joseph B. Cooper, Sandrine Couffin-Cardiergues, Fatoumata Coulibaly, Mariam Coulibaly, Tienhan Sandrine Dabakuyo‐Yonli, Djénéba Dabitao, Thierry Damerval, Bionca Davis, Gibrilla F. Deen, Eline Dekeyster, Jean‐François Delfraissy, Christelle Delmas, Rokia Dembele, Mahamadou Diakité, Alpha Diallo, Mamadou Saliou Diallo, Ayouba Diarra
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.