Partnership for Research on Ebola VACcinations

Study Overview
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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.

Official Title
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Partnership for Research on Ebola VACcinations (PREVAC)

Conditions
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Ebola Virus Disease

Intervention / Treatment
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* Biological: Ad26.ZEBOV
* Biological: MVA-BN-Filo
* Biological: rVSVΔG-ZEBOV-GP
* Biological: Placebo
* Biological: rVSV boost


Participation Criteria
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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 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)

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ad26.ZEBOV (rHAd26) vaccine + MVA-BN-Filo (MVA) boost<br>Participants will receive the Ad26.ZEBOV (rHAd26) vaccine at Day 0 followed by an MVA-BN-Filo (MVA) boost at Day 56. | Biological: Ad26.ZEBOV<br>* 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<br>* Other names: rHAd26;Biological: MVA-BN-Filo<br>* 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<br>* Other names: MVA-mBN226B;|
| Placebo Comparator: Placebo (0.5 mL)<br>Participants will receive placebo at Day 0 followed by a placebo boost at Day 56. | Biological: Placebo<br>* 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<br>|
| Experimental: rVSVΔG-ZEBOV-GP (rVSV) vaccine + placebo boost<br>Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by a placebo boost at Day 56. | Biological: rVSVΔG-ZEBOV-GP<br>* 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<br>* Other names: V920;Biological: Placebo<br>* 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<br>|
| Experimental: rVSVΔG-ZEBOV-GP (rVSV) vaccine + rVSV boost<br>Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by an rVSV boost at Day 56. | Biological: rVSVΔG-ZEBOV-GP<br>* 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<br>* Other names: V920;Biological: rVSV boost<br>* 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<br>* Other names: V920;|
| Placebo Comparator: Placebo (1 mL)<br>Participants will receive placebo at Day 0 followed by a placebo boost at Day 56. | Biological: Placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response | 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. | Measured through Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Serious Adverse Events (SAEs) | SAEs as defined in the protocol | Measured through Month 60 | 
| Number of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response | 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. | Measured through Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ebola Vaccine