Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers

• Status: Not yet recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Ebola virus disease (EVD) is emerging regularly in various African countries for various reasons: during contact with mortal remains, during an unsafe burial or following the viral dissemination around a recovered patient.

However, tools to fight the spread of the disease are being made available to countries affected by MVE. A vaccine (Ervebo), developed by the Merck laboratory, demonstrated its efficacy in protecting contacts and contacts of contacts in the "Ebola That's Enough" trial and two monoclonal antibodies (Mabs) have demonstrated their efficacy in reducing mortality in patients with EVM: REGN-E3B and Mab114.

The question of their use in post-exposure prophylaxis (PEP), defined as the treatment of contacts at very high risk of contracting EVD, is essential. Vaccination with Ervebo alone does not appear to be a good option for PEP, particularly because antibody synthesis is delayed, and the vaccine is likely to be inactive for 10 days after administration. Monoclonal antibodies, on the other hand, seem to be a promising avenue in this indication because of their rapid action on the inhibition of virus entry into the cell.

Moreover, Ervebo vaccine and monoclonal antibodies share the same viral target. It is therefore possible that the vaccine is inhibited by the monoclonal antibodies, particularly in the case of concomitant administration. However, no data on vaccine efficacy in combination are available. The question of the interaction between the monoclonal antibody and Ervebo and the delay between the administration of these two strategies remains unresolved.

The hypothesis of this trial is that Ervebo vaccine efficacy is diminished with the concomitant administration of a monoclonal antibody, especially if this administration is close (short time between Mabs and vaccination). We hypothesize that with an optimal delay between Mabs and vaccination, the immunogenicity of the vaccine combined with monoclonal antibodies could be non-inferior to the vaccine alone, thus providing optimal short and long term protection.

The primary objective of this study is to compare the vaccine immune response at 24 weeks induced by Ervebo administered on the same day (D0) or at S3, S6, or S12 of Inmazeb administration, in healthy volunteers, with vaccination with Ervebo alone.

The trial will have 5 arms. The control arm (vaccination alone) will serve as a comparator of vaccine response in the intervention arms. The 4 intervention arms will assess the minimum time between Mab and vaccination.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Agence Nationale de Sécurité Sanitaire de Guinée (ANSS); Alliance for International Medical Action; Clinical and Operational Research Alliance (CORAL); Institut National de la Santé Et de la Recherche Médicale, France; Méthodologie et Evaluation pour la Recherche clinique et Epidémiologique sur le VIH en Afrique (MEREVA); Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire; University of Bordeaux
• Treatments: Vaccines

Criteria

Inclusion Criteria:

• Available for the duration of the protocol follow-up;

• Consent to participate ;

• Agreed not to participate in another clinical research study until the end of the trial follow-up.

Exclusion Criteria:

• Prior history of EVD (self-reported);

• Previous vaccination with r-VSV-ZEBOV or any other Ebola vaccine (self-reported);

• Previous administration of Ebola antibody-based PEP;

• HIV-1 and/or 2 positive serology;

• Pregnant women (positive pregnancy test);

• To the opinion of the investigator, any clinically significant acute/chronic condition that would limit the participant's ability to meet the requirements of the study protocol;

• Immunosuppressive drugs;

• Participation in another clinical research study within the last 30 days;

• Allergy to any component of the vaccine or Mabs;

• Any other reason that, at the investigator's discretion, would compromise the participant's safety and cooperation in the trial.