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
Authors: Badio Moses , Lhomme Edouard , Kieh Mark , Beavogui Abdoul Habib , Kennedy Stephen B. , Doumbia Seydou , Leigh Bailah , Sow Samba O. , Diallo Alpha , Fusco Daniela , Kirchoff Matthew , Termote Monique , Vatrinet Renaud , Wentworth Deborah , Esperou Helène , Lane H. Clifford , Pierson Jerome , Watson-Jones Deborah , Roy Céline , D’Ortenzio Eric , Greenwood Brian , Chêne Genevieve , Richert Laura , Neaton James D. , Yazdanpanah Yazdan ,   the PREVAC study team, Abdoulaye Coulibaly , Aboulhab Jamilia , Akoo Pauline , Akpa Esther , Akpata Robert , Albert Sara , Ale Boni Maxime , C. Andrews Benetta , Anoma Stephane , Assiandi Saw-San , Augier Augustin , Awuondo Ken , Badio Moses , Bagayoko Aminata , Bakare Nyasha , Balde Abby , Bangura Lamin Molecule , Barrington Kesha , Barte de Saint Fare Eric , Baseler Beth , Bauder Ali , Bauduin Claire , Bawo Luke , Habib Beavogui Abdoul , Belson Michael , Bererd Marion , Beyslow Teedoh , Binachon Blandine , Blie Julie , Bockstal Viki , Boire Youba , Boison Patricia , Bolay Fatorma , Boly Aliou , Gael Borg Anne , Bowers Donna , Browne Sarah , Cagniard Barbara , Cahill Kelly , Abdoulaye Camara Aissata , Camara Keira , Camara Modet , Campion Cécilia , Cash Jennifer , Pin Chai Siew , Chambelin Francois , Chieck Keita , Chêne Geneviève , Ciancia Séverine , Ndiaga Cisse Papa , Clide Elfrida , Colin Céline , Coller Beth-Ann , Siaka Conde Djélikan , Cone Katherine , Connor Laurie , Connor Nicholas , Boye Cooper Joseph , Couffin-Cardiergues Sandrine , Coulibaly Fatoumata , Coulibaly Mariam , Dabakuyo-Yonli Sandrine , Dabitao Djeneba , Damerval Thierry , Davis Bionca , Fadlu Deen Gibrilla , Dekeyster Eline , Delfraissy Jean-François , Delmas Christelle , Dembele Rokia , Diakite Mahamadou , Diallo Alpha , Saliou Diallo Mamadou , Diarra Ayouba , Diawara Oualy , Dighero-kemp Bonnie , Diop Samba , Diouf Waly , Doepel Laurie , D’Ortenzio Eric , Doumbia Seydou , Moise Doumbia Moussa , Douoguih Macaya , DuChêne Alain , Duvenhage Michael , Eckes Risa Eckes , Egan Avril , Enria Luisa , Espérou Hélène , Etienne Cécile , Eyler Allison , Faye Sylvain , Fernandez José , Fleck Suzanne , Fofana Vemy , Franklin Kokulo , Fusco Daniela , Gaddah Auguste , Gaignet Marylène , Gallagher Katherine , Garcia Gozalbes Julia , Grandits Greg , Gray Maima , Greenwood Brian , Greijer Astrid , Grue Louis , Grund Birgit , Guindo Oumar , Gupta Swati , Haidara Fadima , Hamze Benjamin , Hancox Emma , Hart Gavin , Hébert Jean-Christophe , Heijnen Esther , Hensley Patricia , Hensley Lisa , Higgs Elisabeth , Hilton Trudi , Holley Preston , Hoover Marie , Howard Natasha , Hughes Melissa , Ilo Dicko , Imes Jen , Irvine Skip , Ishola David , Jacob Will , Jato Yvonne , Johnson Melvin , Jusu Morrison , Sidiki Kaba Aboubacar , Kante Myriam , Katoudi Judith , Keita Sakoba , Kennedy Stephen , Jide Keshinro Babajide , Khon Brian , Kiawu Hassan , Kieh Mark , Kirchoff Matt , Kodio Mamoudou , Koivogui Lamine , Kombi Tania , Kopka Stacy , Kowuors Dickens , Lacabaratz Christine , Lacarra Boris , Lambert Laurie , Lane Cliff , Lee Shona , Lees Shelley , Lefevre Annabelle , Leigh Bailah , Lemarcis Frederic , Lévy Yves , Levy-Marchal Claire , Lewally Jemilla , Leyssen Maarten , Lhomme Edouard , Liu Ken , Lowe Brett , Lysander Julia , Madelaine Claire , Mahamadou Ibrah , Manno Daniela , Marchand Johnathan , Marynissen Siegfried , Massaquoi Moses B.F. , Masson Laure , Matard Charly , Matthew Onorato , McCullough John , Mercier Noemie , Michavila Pauline , Miller Tracey , Miranda Alejandra , Mohamed Soumaya , Mooney Tom , Morsch Hans , Muamba Dally , Lukoo Ndamenyaa Rita , Neaton James , Neboua Désiré , Nelson Micki , Newell Kevin , Nguyen Vinh-kim , Nielsen Leslie , Niouma Millimouno , Offergeld Kim , Onorato Matthew , Onwuchekwa Uma , Orsega Susan , Ortega-Perez Inmaculada , Osborne Cynthia , Otieno Tuda , Patel Sushma , Peiffer-Smadj Nathan , Phillips Robert , Pierson Jerome , Piot Peter , Piziali Micheal , Pong Stephany , Proffitt Calvin , Quach Alexandre , Ramers-verhoeven Corina , Randunu Nadeeka , Richert Laura , Rivière Priscille , Robinson Cynthia , Van Roey Griet , Roy Céline , Falk Russell Amy , Samai, Sibiry Samake Mohamed , Sangare Ballan , Sanogo Ibrahim , Sadio Sarro Yeya , Sarro Sadio , Saville Mélanie , Sawadogo Serge , Schvartz Maxime , Schwimmer Christine , Secka Fatou , Seraphin Jacques , Shelley Denise , Siddiqui Sophia , Simon Jakub , Simpson Shelly , Muyisa Sivahera Billy , Skip Irvine , Slater Karen , Smolskis Mary , Smout Elizabeth , Snowden Emily , Soutthiphong Anne-Aygline , Sow Samba , Sow Ydrissa , Splinter Daniel , Spreng Simone , Stapleton Helen , Stoop Jeroen , Sweeney Mary , Tamba Sienneh , Tapia Mili , Tegli Jemee , Termote Monique , Thiebaut Rodolphe , Thompson Greg , Tierney John , Touré Abdoulaye , Traina Stacey , Traore Awa , Traore Moussa , Tyee Tijili , Vallée David , Van Der Donck Katrien V , Vatrinet Renaud , Verbruggen Nadia , Vincent Corine , Vogel Susan , Wallet Cedrick , Watson-Jones Deborah , Wentworth Deborah , Wesseh Cecelia , Whitworth Jimmy , Wiedemann Aurelie , Willems Wouter , Williams Julian , Wilson Barthalomew , Wissedi Njoh , Wolf Jayanthi , Woods Ian , Wurie Alie , Yamadjako Delphine , Yaradouno Marcel , Yazdanpanah Yazdan , Zeggani Zara 
Published: January 2021

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.