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PROVAE: Prophylaxis Vaccine Antibodies Ebola

Sponsor
ANRS, Emerging Infectious Diseases (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04822376
Collaborator
(none)
250
Enrollment
1
Location
3
Arms
5.5
Anticipated Duration (Months)
45.8
Patients Per Site Per Month

Study Details

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
Phase 2

Study Design

Study Type:
Interventional
Anticipated 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.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
Anticipated Study Start Date :
Oct 17, 2021
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
Apr 1, 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 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy [Week 3]

      Proportion of participants with negative RT-PCR

    2. Immunological ancillary study [6 months after vaccination]

      Anti-GP IgG level (FANG reference technique)

    Secondary Outcome Measures

    1. Tolerance [Day 7 post-PEP and day 7 post-vaccination]

      Estimating adverse effects

    2. Lost of follow-up [Week 6]

      Lost of follow-up rate

    3. Humoral immune response [1 and 3 months after vaccination]

      Anti-GP IgG level (FANG reference technique)

    4. Neutralizing antibodies [1, 3 and 6 months after vaccination]

      Neutralizing antibodies level

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Locations

    Site City State Country Postal Code
    1 Centre de Traitement Ebola de N'Zerekore N'Zerekore Guinea

    Sponsors and Collaborators

    • ANRS, Emerging Infectious Diseases

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    ANRS, Emerging Infectious Diseases
    ClinicalTrials.gov Identifier:
    NCT04822376
    Other Study ID Numbers:
    • ANRS 0006S
    First Posted:
    Mar 30, 2021
    Last Update Posted:
    Oct 15, 2021
    Last Verified:
    Oct 1, 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
    Ansuvimab

    Study Results

    No Results Posted as of Oct 15, 2021