Prophylaxis Vaccine Antibodies Ebola (PROVAE)

ANRS, Emerging Infectious Diseases

Status and phase: Unknown; Phase 2

Conditions: Ebola Virus Disease

Treatments: Drug: ansuvimab; Biological: Ervebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04822376

ANRS 0006S

Details and patient eligibility

About

• 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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250 participants in 3 patient groups

High risk arm

Experimental group

Description:

Mabs at day 0 and vaccine at week 6

Treatment:

Biological: Ervebo

Drug: ansuvimab

High risk arm (Immunological ancillary study)

Experimental group

Description:

Mabs at day 0 and vaccine at week 6

Treatment:

Biological: Ervebo

Drug: ansuvimab

Control arm (Immunological ancillary study)

Active Comparator group

Description:

Vaccine at day 0 for contacts eligible for vaccination

Treatment:

Biological: Ervebo