Prophylaxis Vaccine Antibodies Ebola (PROVAE)

• ClinicalTrials.gov Identifier: NCT04822376
• Recruitment Status: Unknown
• First Posted: March 30, 2021
• Last Update Posted: October 15, 2021
• Sponsor: ANRS, Emerging Infectious Diseases
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases

Study Description

Brief Summary:

• 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.

Condition or disease	Intervention/treatment	Phase
Ebola Virus Disease	Drug: ansuvimab; Biological: Ervebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment

Intervention 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)
• Primary Purpose: Prevention
• Official Title: 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
• Estimated Study Start Date: October 17, 2021
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2022

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: VSV-ZEBOV

Outcome Measures

Primary Outcome Measures :

1. Efficacy [ Time Frame: Week 3 ]
   Proportion of participants with negative RT-PCR
2. Immunological ancillary study [ Time Frame: 6 months after vaccination ]
   Anti-GP IgG level (FANG reference technique)

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Contacts

Contact: Marie Jaspard, MD; marie.jaspard@coral.alima.ngo

Locations

Guinea

Centre de Traitement Ebola de N'Zerekore

N'Zerekore, Guinea

Contact: Sakoba Keita, MD +224 624510581 sakoba54@gmail.com

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

More Information

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT04822376
• Other Study ID Numbers: ANRS 0006S
• First Posted: March 30, 2021
• Last Update Posted: October 15, 2021
• Last Verified: October 2021

• 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

Additional relevant MeSH terms:

Virus Diseases; Hemorrhagic Fever, Ebola; Infections; Hemorrhagic Fevers, Viral; RNA Virus Infections; Filoviridae Infections; Mononegavirales Infections; Ansuvimab; Antiviral Agents; Anti-Infective Agents