Partnership for Research on Ebola VACcinations

Phase 2

Completed

• Conditions: Ebola Virus Disease
• Interventions: Biological: Placebo; Biological: Ad26.ZEBOV; Biological: rVSVΔG-ZEBOV-GP; Biological: rVSV boost; Biological: MVA-BN-Filo

• Registration Number: NCT02876328
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Timeline

• Study First Submitted: 2016-08-16
• Study First Submitted QC: 2016-08-18
• Study First Posted: 2016-08-23
• Study Start: 2017-03-27
• Primary Completion: 2019-12-24
• Results First Submitted: 2022-07-14
• Results First Submitted QC: 2022-08-30
• Results First Posted: 2022-09-28
• Study Completion: 2023-12-20
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4789

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (0.5 mL)	Placebo	Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.
Ad26.ZEBOV (rHAd26) vaccine + MVA-BN-Filo (MVA) boost	Ad26.ZEBOV	Participants will receive the Ad26.ZEBOV (rHAd26) vaccine at Day 0 followed by an MVA-BN-Filo (MVA) boost at Day 56.
rVSVΔG-ZEBOV-GP (rVSV) vaccine + rVSV boost	rVSV boost	Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by an rVSV boost at Day 56.
Ad26.ZEBOV (rHAd26) vaccine + MVA-BN-Filo (MVA) boost	MVA-BN-Filo	Participants will receive the Ad26.ZEBOV (rHAd26) vaccine at Day 0 followed by an MVA-BN-Filo (MVA) boost at Day 56.
rVSVΔG-ZEBOV-GP (rVSV) vaccine + placebo boost	rVSVΔG-ZEBOV-GP	Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by a placebo boost at Day 56.
rVSVΔG-ZEBOV-GP (rVSV) vaccine + placebo boost	Placebo	Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by a placebo boost at Day 56.
rVSVΔG-ZEBOV-GP (rVSV) vaccine + rVSV boost	rVSVΔG-ZEBOV-GP	Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by an rVSV boost at Day 56.
Placebo (1 mL)	Placebo	Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response	Measured through Month 12	Antibody responder at 12 months is defined as a participant who experiences a 4-fold increase in antibody level from baseline and for whom the antibody level at 12 months is greater than or equal to 200 EU/mL.

Secondary Outcome Measures

Name	Time	Method
Frequency of Serious Adverse Events (SAEs)	Measured through Month 60	SAEs as defined in the protocol
Number of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response	Measured through Month 60	Antibodies to the Ebola virus glycoprotein will be measured with the Filovirus Animal Nonclinical Group (FANG) ELISA assay if available. Other assays may also be used.

Trial Locations

Locations (6)

Landreah; 🇬🇳 Conakry, Guinea

The Redemption Hospital; 🇱🇷 Monrovia, Liberia

University Clinical Research Center (UCRC); 🇲🇱 Bamako, Mali

Mambolo Clinic; 🇸🇱 Kapesseh, Sierra Leone

Centre pour le Développement des Vaccins (CVD); 🇲🇱 Bamako, Mali

Centre national de formation et de recherche en santé rurale (Maferyniah); 🇬🇳 Conakry, Guinea