Prophylaxis Vaccine Antibodies Ebola

Study Overview
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Brief Summary
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Three measures are currently being implemented to control Ebola outbreaks: Monitoring of contacts Isolation and treatment of sick people Vaccination of the population in high-risk areas. In contacts with high viral exposure and therefore a high risk of incubation and rapid expression of infection, the r-VSV-ZEBOV vaccine does not provide adequate protection because vaccine antibody production is effective 6 to 10 days after administration. Specific monoclonal antibodies (Mab) from the Regeneron and mAb114 research specialties have been shown to be effective in reducing mortality in patients with Ebola virus disease (EVD). Their use in a single parenteral administration and good tolerability make them candidates for use in post-exposure prophylaxis (PEP) in individuals at high risk of viral exposure. A comprehensive strategy for the protection of high-risk contacts must therefore be implemented, including the vaccine and the Mabs, to ensure both immediate and prolonged protection. Indeed, the efficacy of the vaccine is likely to be diminished when co-administered with Mabs, as both strategies share the same viral target (the GP envelope glycoprotein) and the vaccine is replicative (and therefore may be inhibited by Mabs). PROVAE aim to evaluate the effectiveness of a comprehensive strategy to prevent transmission of MVE in contacts at high risk of infection, including (i) post-exposure prophylaxis with Mabs and (ii) vaccination with r-VSV-ZEBOV.

Official Title
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Phase IIa Pilot Study Evaluating the Efficacy of a Monoclonal Antibody and Vaccine-based Post-exposure Prophylaxis Strategy in High-risk Contact Cases of Ebola Virus Disease Infection

Conditions
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Ebola Virus Disease

Intervention / Treatment
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* Drug: ansuvimab
* Biological: Ervebo


Participation Criteria
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Eligibility Criteria
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The inclusion criteria for the efficacy trial are: Have had, within the previous 72 hours, a high-risk contact with an Ebola patient confirmed by RT-PCR; Be 18 years of age or older at the time of inclusion; Have no symptoms of EVD; Give consent to participate in the efficacy trial; Agree not to participate in any other therapeutic or vaccine study until the end of the trial follow-up. The criteria for non-inclusion in the efficacy trial are: Have a history of EVD (self-report); Have been vaccinated with ERVEBO prior to the start of the study; Have participated in another therapeutic or vaccine study within 15 days prior to inclusion. Inclusion criteria for the immunology ancillary study are: High Risk Arm: Be included in the efficacy trial; Be available for extended follow-up as specified in the protocol; Specifically consent to the immunology ancillary study. Control arm: Be 18 years of age or older at the time of inclusion; Have no symptoms of EVD; Eligible for ERVEBO vaccination according to national program criteria; Be available for extended follow-up as specified in the protocol; Consent specifically for the ancillary immunology study. The criteria for non-inclusion in the immunologic ancillary study are: All efficacy trial non-inclusion criteria; HIV positive; Pregnant women.

Ages Eligible for Study
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Minimum Age: 18 Years

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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Efficacy trial : Exploratory, non-comparative, unblinded trial with Mab at D0 and vaccine at W6. Immunological ancillary study : Exploratory, controlled, comparative, non-randomized, 2-group, unblinded study comparing Mab at D0 and vaccine at W6 for high-risk contacts with vaccine at D0 for vaccinated contacts.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High risk arm<br>Mabs at day 0 and vaccine at week 6 | Drug: ansuvimab<br>* Human monoclonal antibody to Zaire strain GP (EBOV GP)<br>* Other names: mab114;Biological: Ervebo<br>* Ebola Zaire vaccine (rVSV∆G-ZEBOV-GP, live, attenuated) ≥ 72 million PFU, composed of the Indiana strain of recombinant vesicular stomatitis virus (rVSV) with a deletion of the envelope glycoprotein (G) of VSV replaced by the surface glycoprotein (GP) of the Kikwit 1995 strain of Ebola virus Zaire (ZEBOV)<br>* Other names: VSV-ZEBOV;|
| Experimental: High risk arm (Immunological ancillary study)<br>Mabs at day 0 and vaccine at week 6 | Drug: ansuvimab<br>* Human monoclonal antibody to Zaire strain GP (EBOV GP)<br>* Other names: mab114;Biological: Ervebo<br>* Ebola Zaire vaccine (rVSV∆G-ZEBOV-GP, live, attenuated) ≥ 72 million PFU, composed of the Indiana strain of recombinant vesicular stomatitis virus (rVSV) with a deletion of the envelope glycoprotein (G) of VSV replaced by the surface glycoprotein (GP) of the Kikwit 1995 strain of Ebola virus Zaire (ZEBOV)<br>* Other names: VSV-ZEBOV;|
| Active Comparator: Control arm (Immunological ancillary study)<br>Vaccine at day 0 for contacts eligible for vaccination | Biological: Ervebo<br>* Ebola Zaire vaccine (rVSV∆G-ZEBOV-GP, live, attenuated) ≥ 72 million PFU, composed of the Indiana strain of recombinant vesicular stomatitis virus (rVSV) with a deletion of the envelope glycoprotein (G) of VSV replaced by the surface glycoprotein (GP) of the Kikwit 1995 strain of Ebola virus Zaire (ZEBOV)<br>* Other names: VSV-ZEBOV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Proportion of participants with negative RT-PCR | Week 3 | 
| Immunological ancillary study | Anti-GP IgG level (FANG reference technique) | 6 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance | Estimating adverse effects | Day 7 post-PEP and day 7 post-vaccination | 
| Lost of follow-up | Lost of follow-up rate | Week 6 | 
| Humoral immune response | Anti-GP IgG level (FANG reference technique) | 1 and 3 months after vaccination | 
| Neutralizing antibodies | Neutralizing antibodies level | 1, 3 and 6 months after vaccination |