Clinical trial NCT02876328: Partnership for Research on Ebola VACcinations
Official title: Partnership for Research on Ebola VACcinations (PREVAC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ebola Virus Disease
Keywords: Ebola Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Partnership for Research on Ebola Virus in Liberia (PREVAIL)
name: Institut National de la Santé Et de la Recherche Médicale, France
name: London School of Hygiene and Tropical Medicine
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2016-08-23
Enrollment: 4789
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and immunogenicity of three vaccine strategies that may prevent Ebola virus disease (EVD) events in children and adults. Participants will receive either the Ad26.ZEBOV (rHAd26) vaccine with a MVA-BN-Filo (MVA) boost, or the rVSVΔG-ZEBOV-GP (rVSV) vaccine with or without boosting, or placebo.

Detailed description: The purpose of this study is to evaluate the safety and immunogenicity of two Ebola virus disease (EVD) vaccines, Ad26.ZEBOV (rHAd26) and rVSVΔG-ZEBOV-GP (rVSV), in children and adults. These vaccines will be studied using three different strategies: the rHAd26 vaccine plus a MVA-BN-Filo (MVA) boost, and the rVSV vaccine with or without boosting.

Participants will be randomized into five groups: the Ad26.ZEBOV vaccine with an MVA boost, the rVSV vaccine with or without boosting, or one of two placebo groups. At Day 0 (study entry), participants will receive the Ad26.ZEBOV vaccine, the rVSV vaccine, or placebo.

At Day 56, participants assigned to the rVSV vaccine without a boost and the two placebo groups will receive placebo. Those initially given the Ad26.ZEBOV vaccine will receive the MVA boost. Those assigned to the boosted rVSV group will receive the rVSV boost.

Additional study visits will occur on Days 7, 14, 28, and 63, and at Months 3, 6, 12, 24, 36, 48, and 60. Study visits may include blood collection and other assessments.

Some participants may take part in substudies, which will include blood or saliva collection.

After the Month 12 visit, during the long-term follow-up, the participants who received the placebo will be vaccinated with a single dose of rVSVΔG-ZEBOV-GP vaccine in Liberia and Mali and with the Ad26.ZEBOV/MVA-BN-Filo vaccine strategy in Guinea and Sierra Leone. The participants who received an incomplete Ad26.ZEBOV/MVA-BN-Filo vaccine strategy will be offered a single dose of the Ad26.ZEBOV or MVA-BN-Filo vaccine in Guinea and Sierra Leone and a single dose of rVSVΔG-ZEBOV-GP in Liberia and Mali.

Eligibility criteria: Inclusion Criteria:

* Informed consent/assent
* Age greater than or equal to 1 year
* Planned residency in the area of the study site for the next 12 months
* Willingness to comply with the protocol requirements

Exclusion Criteria:

* Fever greater than 38º Celsius
* History of EVD (self-report)
* Pregnancy (a negative urine pregnancy test is required for females of child-bearing potential, i.e., females who have experienced menarche or who are aged 14 years and older)
* Positive HIV test for participants less than 18 years of age
* Reported current breast-feeding
* Prior vaccination against Ebola (self-report)
* Any vaccination in the past 28 days or planned within the 28 days after randomization (initial vaccination)
* In the judgement of the clinician, any clinically significant acute/chronic condition that would limit the ability of the participant to meet the requirements of the study protocol

Inclusion Criteria for Revaccination Post 12 Month Visit:

* Participants who received the placebo
* Participants who received an incomplete Ad26.ZEBOV/MVA-BN-Filo vaccine strategy

Temporary Exclusion Criteria for Revaccination Post 12 Month Visit:

* Fever greater than 38º Celsius
* Pregnancy (a negative urine pregnancy test is required for females of child-bearing potential, i.e., females who have experienced menarche or who are aged 14 years and older)
* Reported current breast-feeding (self-report)
* Any vaccination in the past 28 days or planned within the 28 days after trial vaccination

Exclusion Criteria for Revaccination Post 12 Month Visit:

* EVD notified in the electronic case report form
* For minor participants: change in HIV status since enrollment (self-report)
* Previous Ebola vaccination outside of the study including incomplete vaccine strategies
* Known medical history or significant risk factors for a thrombotic and/or thrombocytopenic event (for participants who will receive the Ad26.ZEBOV or MVA-BN-Filo vaccine)

Primary outcomes:
measure: Percentage of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response
timeFrame: Measured through Month 12
Secondary outcomes:
measure: Frequency of Serious Adverse Events (SAEs)
timeFrame: Measured through Month 60
measure: Number of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response
timeFrame: Measured through Month 60
Other outcomes:
Locations:
city: Conakry
country: Guinea
facility: Centre national de formation et de recherche en santé rurale (Maferyniah)
city: Conakry
country: Guinea
facility: Landreah
city: Monrovia
country: Liberia
facility: The Redemption Hospital
city: Bamako
country: Mali
facility: Centre pour le Développement des Vaccins (CVD)
city: Bamako
country: Mali
facility: University Clinical Research Center (UCRC)
city: Kapesseh
country: Sierra Leone
facility: Mambolo Clinic
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Yazdan Yazdanpannah
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre de Formation et de Recherche en Santé Rurale de Mafèrinyah
name: Abdoul Habib Beavogui
role: PRINCIPAL_INVESTIGATOR
affiliation: Redemption Hospital
name: Mark Kieh
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sierra Leone
name: Bailah Leigh
role: PRINCIPAL_INVESTIGATOR
affiliation: Redemption Hospital
name: Stephen B. Kennedy
role: PRINCIPAL_INVESTIGATOR
affiliation: Universite des Sciences, des Techniques et des Technologies de Bamako
name: Seydou Doumbia
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre pour le Developpement des Vaccins
name: Samba O. Sow
role: PRINCIPAL_INVESTIGATOR
References:
citation: Badio M, Lhomme E, Kieh M, Beavogui AH, Kennedy SB, Doumbia S, Leigh B, Sow SO, Diallo A, Fusco D, Kirchoff M, Termote M, Vatrinet R, Wentworth D, Esperou H, Lane HC, Pierson J, Watson-Jones D, Roy C, D'Ortenzio E, Greenwood B, Chene G, Richert L, Neaton JD, Yazdanpanah Y; PREVAC study team. 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. Trials. 2021 Jan 23;22(1):86. doi: 10.1186/s13063-021-05035-9.
citation: PREVAC Study Team; Kieh M, Richert L, Beavogui AH, Grund B, Leigh B, D'Ortenzio E, Doumbia S, Lhomme E, Sow S, Vatrinet R, Roy C, Kennedy SB, Faye S, Lees S, Millimouno NP, Camara AM, Samai M, Deen GF, Doumbia M, Esperou H, Pierson J, Watson-Jones D, Diallo A, Wentworth D, McLean C, Simon J, Wiedemann A, Dighero-Kemp B, Hensley L, Lane HC, Levy Y, Piot P, Greenwood B, Chene G, Neaton J, Yazdanpanah Y. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. 2022 Dec 29;387(26):2411-2424. doi: 10.1056/NEJMoa2200072. Epub 2022 Dec 14.