Prophylaxis Vaccine Antibodies Ebola (PROVAE)

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

• 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ebola Virus Disease
• Intervention / Treatment: Drug: ansuvimab; Biological: Ervebo

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marie Jaspard, MD; Email: marie.jaspard@coral.alima.ngo

Study Locations

• Guinea
  • N'Zerekore, Guinea
    • Centre de Traitement Ebola de N'Zerekore
    • Contact: Sakoba Keita, MD; Phone Number: +224 624510581; Email: sakoba54@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High risk arm; Mabs at day 0 and vaccine at week 6	Drug: ansuvimab; Human monoclonal antibody to Zaire strain GP (EBOV GP); Other Names: mab114; Biological: Ervebo; 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); Other Names: VSV-ZEBOV
EXPERIMENTAL: High risk arm (Immunological ancillary study); Mabs at day 0 and vaccine at week 6	Drug: ansuvimab; Human monoclonal antibody to Zaire strain GP (EBOV GP); Other Names: mab114; Biological: Ervebo; 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); Other Names: VSV-ZEBOV
ACTIVE_COMPARATOR: Control arm (Immunological ancillary study); Vaccine at day 0 for contacts eligible for vaccination	Biological: Ervebo; 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); Other Names: VSV-ZEBOV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 17, 2021
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (ACTUAL): March 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Virus Diseases; Hemorrhagic Fever, Ebola; Anti-Infective Agents; Antiviral Agents; Ansuvimab
• Other Study ID Numbers: ANRS 0006S

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No