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

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 EVD. 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 EVD: REGN-E3B (Inmazeb) and Mab114 (Ebanga).

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 does not appear to be a good standalone 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 expresses the viral target recognized by mAbs, GP EBOV. It is therefore possible that the vaccine response (production of vaccine antibodies) is inhibited by mAbs, which bind to GP EBOV and prevent vaccine replication, 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 when administered with monoclonal antibodies could be non-inferior to the vaccine alone, thus providing optimal short and long term protection.

The main objective of this study is to evaluate the extent of effect, if any, of Inmazeb administration on vaccine-induced neutralizing antibody responses to Zaire Ebola virus by Ervebo vaccine. If an interaction is observed, this will possibly enable determination of the time interval required between the administration of Inmazeb and Ervebo vaccine.

The trial will have 6 arms. A control arm of vaccination alone will serve to characterize the immune response to the vaccine and it will be used as a comparator of vaccine immune response in the intervention arms. A control arm of mAb alone will serve to characterize the pharmacokinetic profile of mAb in the Guinean population. The 4 arms including different doses of Inmazeb plus vaccination were designed to mimic a time interval between Ervebo and Inmazeb administration (15, 57 and 169 days after Inmazeb).

Conditions

• Ebola Virus Disease

Interventions

BIOLOGICAL

Ervebo

Administration of r-VSV-ZEBOV vaccine

DRUG

Inmazeb

Administration of Inmazeb

Sponsors & Collaborators

• University of Bordeaux

  collaborator OTHER

• Institut National de la Santé Et de la Recherche Médicale, France

  collaborator OTHER_GOV

• Clinical and Operational Research Alliance (CORAL)

  collaborator UNKNOWN

• Institut Pasteur

  collaborator INDUSTRY

• Regeneron Pharmaceuticals

  collaborator INDUSTRY

• MSD France

  collaborator INDUSTRY

• Alliance for International Medical Action

  collaborator OTHER

• Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG)

  collaborator UNKNOWN

• PACCI Program

  collaborator OTHER

• ANRS, Emerging Infectious Diseases

  lead OTHER_GOV

Principal Investigators

• Marie JASPARD, PHD · CORAL

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2027-01-31

Primary Completion

2027-08-31

Completion

2027-08-31