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, Edouard Lhomme, Mark Kieh, Abdoul Habib Beavogui, Stephen B Kennedy, Seydou Doumbia, Bailah Leigh, Samba O Sow, Alpha Diallo, Daniela Fusco, Matthew Kirchoff, Monique Termote, Renaud Vatrinet, Deborah Wentworth, Helène Esperou, H Clifford Lane, Jerome Pierson, Deborah Watson-Jones, Céline Roy, Eric D'Ortenzio, Brian Greenwood, Genevieve Chêne, Laura Richert, James D Neaton, Yazdan Yazdanpanah, PREVAC study team, Coulibaly Abdoulaye, 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 Beavogui, 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 Cisse, Elfrida Clide, Céline Colin, Beth-Ann Coller, Djélikan Siaka Conde, Katherine Cone, Laurie Connor, Nicholas Connor, Joseph Boye Cooper, Sandrine Couffin-Cardiergues, Fatoumata Coulibaly, Mariam Coulibaly, Sandrine Dabakuyo-Yonli, Djeneba Dabitao, Thierry Damerval, Bionca Davis, Gibrilla Fadlu Deen, Eline Dekeyster, Jean-François Delfraissy, Christelle Delmas, Rokia Dembele, Mahamadou Diakite, Alpha Diallo, Mamadou Saliou Diallo, Ayouba Diarra, Oualy Diawara, Bonnie Dighero-Kemp, Samba Diop, Waly Diouf, Laurie Doepel, Eric D'Ortenzio, Seydou Doumbia, Moussa Moise Doumbia, Macaya Douoguih, Alain DuChêne, Michael Duvenhage, Risa Eckes Eckes, Avril Egan, Luisa Enria, Hélène Espérou, Cécile Etienne, Allison Eyler, Sylvain Faye, José Fernandez, Suzanne Fleck, Vemy Fofana, Kokulo Franklin, Daniela Fusco, Auguste Gaddah, Marylène Gaignet, Katherine Gallagher, Julia Garcia Gozalbes, Greg Grandits, Maima Gray, Brian Greenwood, Astrid Greijer, Louis Grue, Birgit Grund, Oumar Guindo, Swati Gupta, Fadima Haidara, Benjamin Hamze, Emma Hancox, Gavin Hart, Jean-Christophe Hébert, Esther Heijnen, Patricia Hensley, Lisa Hensley, Elisabeth Higgs, Trudi Hilton, Preston Holley, Marie Hoover, Natasha Howard, Melissa Hughes, Dicko Ilo, Jen Imes, Skip Irvine, David Ishola, Will Jacob, Yvonne Jato, Melvin Johnson, Morrison Jusu, Aboubacar Sidiki Kaba, Myriam Kante, Judith Katoudi, Sakoba Keita, Stephen Kennedy, Babajide Jide Keshinro, Brian Khon, Hassan Kiawu, Mark Kieh, Matt Kirchoff, Mamoudou Kodio, Lamine Koivogui, Tania Kombi, Stacy Kopka, Dickens Kowuors, Christine Lacabaratz, Boris Lacarra, Laurie Lambert, Cliff Lane, Shona Lee, Shelley Lees, Annabelle Lefevre, Bailah Leigh, Frederic Lemarcis, Yves Lévy, Claire Levy-Marchal, Jemilla Lewally, Maarten Leyssen, Edouard Lhomme, Ken Liu, Brett Lowe, Julia Lysander, Claire Madelaine, Ibrah Mahamadou, Daniela Manno, Johnathan Marchand, Siegfried Marynissen, Moses B F Massaquoi, Laure Masson, Charly Matard, Onorato Matthew, John McCullough, Noemie Mercier, Pauline Michavila, Tracey Miller, Alejandra Miranda, Soumaya Mohamed, Tom Mooney, Hans Morsch, Dally Muamba, Rita Lukoo Ndamenyaa, James Neaton, Désiré Neboua, Micki Nelson, Kevin Newell, Vinh-Kim Nguyen, Leslie Nielsen, Millimouno Niouma, Kim Offergeld, Matthew Onorato, Uma Onwuchekwa, Susan Orsega, Inmaculada Ortega-Perez, Cynthia Osborne, Tuda Otieno, Sushma Patel, Nathan Peiffer-Smadj, Robert Phillips, Jerome Pierson, Peter Piot, Micheal Piziali, Stephany Pong, Calvin Proffitt, Alexandre Quach, Corina Ramers-Verhoeven, Nadeeka Randunu, Laura Richert, Priscille Rivière, Cynthia Robinson, Griet Van Roey, Céline Roy, Amy Falk Russell, Mohamed Samai Sibiry Samake, Ballan Sangare, Ibrahim Sanogo, Yeya Sadio Sarro, Sadio Sarro, Mélanie Saville, Serge Sawadogo, Maxime Schvartz, Christine Schwimmer, Fatou Secka, Jacques Seraphin, Denise Shelley, Sophia Siddiqui, Jakub Simon, Shelly Simpson, Billy Muyisa Sivahera, Irvine Skip, Karen Slater, Mary Smolskis, Elizabeth Smout, Emily Snowden, Anne-Aygline Soutthiphong, Samba Sow, Ydrissa Sow, Daniel Splinter, Simone Spreng, Helen Stapleton, Jeroen Stoop, Mary Sweeney, Sienneh Tamba, Mili Tapia, Jemee Tegli, Monique Termote, Rodolphe Thiebaut, Greg Thompson, John Tierney, Abdoulaye Touré, Stacey Traina, Awa Traore, Moussa Traore, Tijili Tyee, David Vallée, Katrien V Van Der Donck, Renaud Vatrinet, Nadia Verbruggen, Corine Vincent, Susan Vogel, Cedrick Wallet, Deborah Watson-Jones, Deborah Wentworth, Cecelia Wesseh, Jimmy Whitworth, Aurelie Wiedemann, Wouter Willems, Julian Williams, Barthalomew Wilson, Njoh Wissedi, Jayanthi Wolf, Ian Woods, Alie Wurie, Delphine Yamadjako, Marcel Yaradouno, Yazdan Yazdanpanah, Zara Zeggani, Moses Badio, Edouard Lhomme, Mark Kieh, Abdoul Habib Beavogui, Stephen B Kennedy, Seydou Doumbia, Bailah Leigh, Samba O Sow, Alpha Diallo, Daniela Fusco, Matthew Kirchoff, Monique Termote, Renaud Vatrinet, Deborah Wentworth, Helène Esperou, H Clifford Lane, Jerome Pierson, Deborah Watson-Jones, Céline Roy, Eric D'Ortenzio, Brian Greenwood, Genevieve Chêne, Laura Richert, James D Neaton, Yazdan Yazdanpanah, PREVAC study team, Coulibaly Abdoulaye, 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 Beavogui, 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 Cisse, Elfrida Clide, Céline Colin, Beth-Ann Coller, Djélikan Siaka Conde, Katherine Cone, Laurie Connor, Nicholas Connor, Joseph Boye Cooper, Sandrine Couffin-Cardiergues, Fatoumata Coulibaly, Mariam Coulibaly, Sandrine Dabakuyo-Yonli, Djeneba Dabitao, Thierry Damerval, Bionca Davis, Gibrilla Fadlu Deen, Eline Dekeyster, Jean-François Delfraissy, Christelle Delmas, Rokia Dembele, Mahamadou Diakite, Alpha Diallo, Mamadou Saliou Diallo, Ayouba Diarra, Oualy Diawara, Bonnie Dighero-Kemp, Samba Diop, Waly Diouf, Laurie Doepel, Eric D'Ortenzio, Seydou Doumbia, Moussa Moise Doumbia, Macaya Douoguih, Alain DuChêne, Michael Duvenhage, Risa Eckes Eckes, Avril Egan, Luisa Enria, Hélène Espérou, Cécile Etienne, Allison Eyler, Sylvain Faye, José Fernandez, Suzanne Fleck, Vemy Fofana, Kokulo Franklin, Daniela Fusco, Auguste Gaddah, Marylène Gaignet, Katherine Gallagher, Julia Garcia Gozalbes, Greg Grandits, Maima Gray, Brian Greenwood, Astrid Greijer, Louis Grue, Birgit Grund, Oumar Guindo, Swati Gupta, Fadima Haidara, Benjamin Hamze, Emma Hancox, Gavin Hart, Jean-Christophe Hébert, Esther Heijnen, Patricia Hensley, Lisa Hensley, Elisabeth Higgs, Trudi Hilton, Preston Holley, Marie Hoover, Natasha Howard, Melissa Hughes, Dicko Ilo, Jen Imes, Skip Irvine, David Ishola, Will Jacob, Yvonne Jato, Melvin Johnson, Morrison Jusu, Aboubacar Sidiki Kaba, Myriam Kante, Judith Katoudi, Sakoba Keita, Stephen Kennedy, Babajide Jide Keshinro, Brian Khon, Hassan Kiawu, Mark Kieh, Matt Kirchoff, Mamoudou Kodio, Lamine Koivogui, Tania Kombi, Stacy Kopka, Dickens Kowuors, Christine Lacabaratz, Boris Lacarra, Laurie Lambert, Cliff Lane, Shona Lee, Shelley Lees, Annabelle Lefevre, Bailah Leigh, Frederic Lemarcis, Yves Lévy, Claire Levy-Marchal, Jemilla Lewally, Maarten Leyssen, Edouard Lhomme, Ken Liu, Brett Lowe, Julia Lysander, Claire Madelaine, Ibrah Mahamadou, Daniela Manno, Johnathan Marchand, Siegfried Marynissen, Moses B F Massaquoi, Laure Masson, Charly Matard, Onorato Matthew, John McCullough, Noemie Mercier, Pauline Michavila, Tracey Miller, Alejandra Miranda, Soumaya Mohamed, Tom Mooney, Hans Morsch, Dally Muamba, Rita Lukoo Ndamenyaa, James Neaton, Désiré Neboua, Micki Nelson, Kevin Newell, Vinh-Kim Nguyen, Leslie Nielsen, Millimouno Niouma, Kim Offergeld, Matthew Onorato, Uma Onwuchekwa, Susan Orsega, Inmaculada Ortega-Perez, Cynthia Osborne, Tuda Otieno, Sushma Patel, Nathan Peiffer-Smadj, Robert Phillips, Jerome Pierson, Peter Piot, Micheal Piziali, Stephany Pong, Calvin Proffitt, Alexandre Quach, Corina Ramers-Verhoeven, Nadeeka Randunu, Laura Richert, Priscille Rivière, Cynthia Robinson, Griet Van Roey, Céline Roy, Amy Falk Russell, Mohamed Samai Sibiry Samake, Ballan Sangare, Ibrahim Sanogo, Yeya Sadio Sarro, Sadio Sarro, Mélanie Saville, Serge Sawadogo, Maxime Schvartz, Christine Schwimmer, Fatou Secka, Jacques Seraphin, Denise Shelley, Sophia Siddiqui, Jakub Simon, Shelly Simpson, Billy Muyisa Sivahera, Irvine Skip, Karen Slater, Mary Smolskis, Elizabeth Smout, Emily Snowden, Anne-Aygline Soutthiphong, Samba Sow, Ydrissa Sow, Daniel Splinter, Simone Spreng, Helen Stapleton, Jeroen Stoop, Mary Sweeney, Sienneh Tamba, Mili Tapia, Jemee Tegli, Monique Termote, Rodolphe Thiebaut, Greg Thompson, John Tierney, Abdoulaye Touré, Stacey Traina, Awa Traore, Moussa Traore, Tijili Tyee, David Vallée, Katrien V Van Der Donck, Renaud Vatrinet, Nadia Verbruggen, Corine Vincent, Susan Vogel, Cedrick Wallet, Deborah Watson-Jones, Deborah Wentworth, Cecelia Wesseh, Jimmy Whitworth, Aurelie Wiedemann, Wouter Willems, Julian Williams, Barthalomew Wilson, Njoh Wissedi, Jayanthi Wolf, Ian Woods, Alie Wurie, Delphine Yamadjako, Marcel Yaradouno, Yazdan Yazdanpanah, Zara Zeggani
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.
Keywords: Clinical trials; Ebola; Protocol; Randomized controlled trials; Vaccine.
Conflict of interest statement
None declared.
Figures
References
- Lévy Y, Lane C, Piot P, et al. Prevention of Ebola virus disease through vaccination: where we are in 2018. Lancet. 2018. 10.1016/S0140-6736(18)31710-0.
- Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017. 10.1016/S0140-6736(16)32621-6.
- Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26-and modified vaccinia Ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA. 2016. 10.1001/jama.2016.4218.
- Pollard AJ, Launay O, Lelievre J-D, et al. Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2020. 10.1016/s1473-3099(20)30476-x.
- Mutua G, Anzala O, Luhn K, et al. Randomized clinical trial examining safety and immunogenicity of heterologous prime-boost Ebola vaccines, Ad26.ZEBOV and MVA-BN-Filo: 12-month data from Nairobi, Kenya. J Infect Dis. 2019. 10.1093/infdis/jiz071.
- Anywaine Z, Whitworth H, Kaleebu P, et al. Safety and immunogenicity of a 2-dose heterologous vaccination regimen with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a phase 1 randomized clinical trial in Uganda and Tanzania. J Infect Dis. 2019. 10.1093/infdis/jiz070.
- Kennedy SB, Bolay F, Kieh M, et al. Phase 2 placebo-controlled trial of two vaccines to prevent Ebola in Liberia. N Engl J Med. 2017. 10.1056/nejmoa1614067.
- Logue J, Tuznik K, Follmann D, et al. Use of the Filovirus Animal Non-Clinical Group (FANG) Ebola virus immuno-assay requires fewer study participants to power a study than the Alpha Diagnostic International assay. J Virol Methods. 2018. 10.1016/j.jviromet.2018.02.018.
- Dosoo DK, Kayan K, Adu-Gyasi D, et al. Haematological and biochemical reference values for healthy adults in the Middle Belt of Ghana. PLoS One. 2012. 10.1371/journal.pone.0036308.
- Dosoo DK, Asante KP, Kayan K, et al. Biochemical and hematologic parameters for children in the middle belt of Ghana. Am J Trop Med Hyg. 2014. 10.4269/ajtmh.13-0098.
- Kone B, Maiga M, Baya B, Sarro YDS, Coulibaly N, Kone A, et al. Establishing reference ranges of hematological parameters from Malian healthy adults. J Blood Lymph. 2017. 10.4172/2165-7831.1000154.
- Agnandji ST, Fernandes JF, Bache EB, et al. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: a phase I randomised trial. PLoS Med. 2017. 10.1371/journal.pmed.1002402.
- Garske T, Cori A, Ariyarajah A, et al. Heterogeneities in the case fatality ratio in the west African Ebola outbreak 2013–2016. Philos Trans R Soc B Biol Sci. 2017. 10.1098/rstb.2016.0308.
- Enria L, Lees S, Smout E, et al. Power, fairness and trust: understanding and engaging with vaccine trial participants and communities in the setting up the EBOVAC-Salone vaccine trial in Sierra Leone. BMC Public Health. 2016. 10.1186/s12889-016-3799-x.
- Laverack G, Manoncourt E. Key experiences of community engagement and social mobilization in the Ebola response. Glob Health Promot. 2016. 10.1177/1757975915606674.
Source: PubMed