Partnership for Research on Ebola VACcinations

NCT ID: NCT02876328

Last Updated: 2024-06-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

4789 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-27

Study Completion Date

2023-12-20

Brief Summary

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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

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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.

Conditions

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Ebola Virus Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ad26.ZEBOV (rHAd26) vaccine + MVA-BN-Filo (MVA) boost

Participants will receive the Ad26.ZEBOV (rHAd26) vaccine at Day 0 followed by an MVA-BN-Filo (MVA) boost at Day 56.

Group Type EXPERIMENTAL

Ad26.ZEBOV

Intervention Type BIOLOGICAL

0.5 mL at a dose of 5x10\^10 vp administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

MVA-BN-Filo

Intervention Type BIOLOGICAL

0.5 mL at a dose of 1x10\^8 InfU administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Placebo (0.5 mL)

Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

rVSVΔG-ZEBOV-GP (rVSV) vaccine + placebo boost

Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by a placebo boost at Day 56.

Group Type EXPERIMENTAL

rVSVΔG-ZEBOV-GP

Intervention Type BIOLOGICAL

1 mL at a nominal dose of 2x10\^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Placebo

Intervention Type BIOLOGICAL

0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

rVSVΔG-ZEBOV-GP (rVSV) vaccine + rVSV boost

Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by an rVSV boost at Day 56.

Group Type EXPERIMENTAL

rVSVΔG-ZEBOV-GP

Intervention Type BIOLOGICAL

1 mL at a nominal dose of 2x10\^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

rVSV boost

Intervention Type BIOLOGICAL

1 mL at a nominal dose of 2x10\^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Placebo (1 mL)

Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Interventions

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Ad26.ZEBOV

0.5 mL at a dose of 5x10\^10 vp administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Intervention Type BIOLOGICAL

MVA-BN-Filo

0.5 mL at a dose of 1x10\^8 InfU administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Intervention Type BIOLOGICAL

rVSVΔG-ZEBOV-GP

1 mL at a nominal dose of 2x10\^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Intervention Type BIOLOGICAL

Placebo

0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Intervention Type BIOLOGICAL

rVSV boost

1 mL at a nominal dose of 2x10\^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

Intervention Type BIOLOGICAL

Other Intervention Names

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rHAd26 MVA MVA-mBN226B rVSV V920 rVSVΔG-ZEBOV-GP rVSV V920

Eligibility Criteria

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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


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

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


* 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


* 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)
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Partnership for Research on Ebola Virus in Liberia (PREVAIL)

NETWORK

Sponsor Role collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yazdan Yazdanpannah

Role: PRINCIPAL_INVESTIGATOR

Institut National de la Santé Et de la Recherche Médicale, France

Abdoul Habib Beavogui

Role: PRINCIPAL_INVESTIGATOR

Centre de Formation et de Recherche en Santé Rurale de Mafèrinyah

Mark Kieh

Role: PRINCIPAL_INVESTIGATOR

Redemption Hospital

Bailah Leigh

Role: PRINCIPAL_INVESTIGATOR

University of Sierra Leone

Stephen B. Kennedy

Role: PRINCIPAL_INVESTIGATOR

Redemption Hospital

Seydou Doumbia

Role: PRINCIPAL_INVESTIGATOR

Universite des Sciences, des Techniques et des Technologies de Bamako

Samba O. Sow

Role: PRINCIPAL_INVESTIGATOR

Centre pour le Developpement des Vaccins

Locations

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Centre national de formation et de recherche en santé rurale (Maferyniah)

Conakry, , Guinea

Site Status

Landreah

Conakry, , Guinea

Site Status

The Redemption Hospital

Monrovia, , Liberia

Site Status

Centre pour le Développement des Vaccins (CVD)

Bamako, , Mali

Site Status

University Clinical Research Center (UCRC)

Bamako, , Mali

Site Status

Mambolo Clinic

Kapesseh, , Sierra Leone

Site Status

Countries

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Guinea Liberia Mali Sierra Leone

References

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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.

Reference Type RESULT
PMID: 33485369 (View on PubMed)

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.

Reference Type RESULT
PMID: 36516078 (View on PubMed)

Valayer S, Alexandre M, Prague M, Beavogui AH, Doumbia S, Kieh M, Greenwood B, Leigh B, Poupelin M, Schwimmer C, Sow SO, Berry IM, Kuhn JH, Fusco D, Cauwelaert ND, Watson-Jones D, Thiebaut R, Levy Y, Yazdanpanah Y, Richert L, Lhomme E; PREVAC study team. Evaluation of waning of IgG antibody responses after rVSVDeltaG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial. Emerg Microbes Infect. 2025 Dec;14(1):0. doi: 10.1080/22221751.2024.2432353. Epub 2024 Dec 9.

Reference Type DERIVED
PMID: 39559990 (View on PubMed)

Wiedemann A, Lhomme E, Huchon M, Foucat E, Bererd-Camara M, Guillaumat L, Yaradouno M, Tambalou J, Rodrigues C, Ribeiro A, Beavogui AH, Lacabaratz C, Thiebaut R, Richert L, Levy Y; Prevac study team. Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases. Nat Commun. 2024 Sep 3;15(1):7666. doi: 10.1038/s41467-024-51453-z.

Reference Type DERIVED
PMID: 39227399 (View on PubMed)

Lee AW, Liu K, Lhomme E, Blie J, McCullough J, Onorato MT, Connor L, Simon JK, Dubey S, VanRheenen S, Deutsch J, Owens A, Morgan A, Welebob C, Hyatt D, Nair S, Hamze B, Guindo O, Sow SO, Beavogui AH, Leigh B, Samai M, Akoo P, Serry-Bangura A, Fleck S, Secka F, Lowe B, Watson-Jones D, Roy C, Hensley LE, Kieh M, Coller BG; PREVAC Study Team. Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVDeltaG-ZEBOV-GP Ebola Vaccine (ERVEBO(R)): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults. Clin Infect Dis. 2024 Apr 10;78(4):870-879. doi: 10.1093/cid/ciad693.

Reference Type DERIVED
PMID: 37967326 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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PREVACEBL3005

Identifier Type: OTHER

Identifier Source: secondary_id

C15-33

Identifier Type: -

Identifier Source: org_study_id

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