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

NCT05202288 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ANRS 0064S IMOVA
• Study Type: interventional
• Target: 132
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

Post Exposure Prophylaxis; Ebola vaccine

Outcome Measures

Primary Outcomes (1)

• Neutralizing antibodies rates

  The level will be evaluated with a pseudo-type plaque reduction neutralization test

  Day 1, Day 29, Day 57, Day 85 and during participant's early termination

Secondary Outcomes (7)

• Anti-EBOV GP IgG rates

  Day 1, Day 29, Day 57, Day 85 and during participant's early termination

• RT-PCR VSV

  Day 3

• T cell response

  Day 1, Day 29

• Proportion of participants with grade 3 or 4 adverse events

  Day 3, Day 7, Day 29, Day57, Day 85 and anytime after infusion and vaccination

• Proportion of participants lost to follow-up

  Day 85 after vaccination

Study Arms (6)

Ervebo 72 million PFU

ACTIVE COMPARATOR

The control arm (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. Administration at D1.

Biological: Ervebo

Inmazeb 150mg/kg

ACTIVE COMPARATOR

This second control arm of mAb alone will serve to characterize the pharmacokinetic profile of mAb in the Guinean population. Administration at D1.

Drug: Inmazeb

Inmazeb 150mg/kg + Ervebo 72 million PFU

EXPERIMENTAL

The Arm 3, is a concomitant administration of the antibody and the vaccine at D1.

Biological: Ervebo; Drug: Inmazeb

Inmazeb 50mg/kg + Ervebo 72 million PFU

EXPERIMENTAL

The Arm 4, is a concomitant injection of different-dose of the antibody and the vaccine. This design mimics a time interval of 15 days between Ervebo and Inmazeb administration. The administration will be at D1. These may help define a time interval between Ervebo administration and Inmazeb infusion.

Biological: Ervebo; Drug: Inmazeb

Inmazeb 10mg/kg + Ervebo 72 million PFU

EXPERIMENTAL

The Arm 5, is a concomitant injection of different-dose of the antibody and the vaccine. This design mimics a time interval of 57 days between Ervebo and Inmazeb administration. The administration will be at D1. These may help define a time interval between Ervebo administration and Inmazeb infusion.

Biological: Ervebo; Drug: Inmazeb

Inmazeb 0.7mg/kg + Ervebo 72 million PFU

EXPERIMENTAL

The Arm 6, is a concomitant injection of different-dose of the antibody and the vaccine. This design mimics a time interval of 169 days between Ervebo and Inmazeb administration. The administration will be at D1. These may help define a time interval between Ervebo administration and Inmazeb infusion.

Biological: Ervebo; Drug: Inmazeb

Interventions

Ervebo BIOLOGICAL

Administration of r-VSV-ZEBOV vaccine

Also known as: r-VSV-ZEBOV vaccine

Ervebo 72 million PFU; Inmazeb 0.7mg/kg + Ervebo 72 million PFU; Inmazeb 10mg/kg + Ervebo 72 million PFU; Inmazeb 150mg/kg + Ervebo 72 million PFU; Inmazeb 50mg/kg + Ervebo 72 million PFU

Inmazeb DRUG

Administration of Inmazeb

Also known as: REGN-E3B

Inmazeb 0.7mg/kg + Ervebo 72 million PFU; Inmazeb 10mg/kg + Ervebo 72 million PFU; Inmazeb 150mg/kg; Inmazeb 150mg/kg + Ervebo 72 million PFU; Inmazeb 50mg/kg + Ervebo 72 million PFU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior history of EVD (self-reported);
• Previous vaccination with r-VSV-ZEBOV or any other Ebola vaccine (self-reported);
• Previous administration of Ebola antibody;
• HIV-1 and/or 2 positive serology;
• Pregnant women (positive pregnancy test);
• Breastfeeding women;
• 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;
• Taking Immunosuppressive therapy;
• Participation in another clinical research study within the last 30 days;
• Allergy to any component of the vaccine or Mabs;
• Person deprived of freedom by a judicial or administrative decision;
• Any other reason that, at the investigator\'s discretion, would compromise the participant\'s safety and cooperation in the trial.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• University of Bordeaux: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Clinical and Operational Research Alliance (CORAL): collaborator
• Institut Pasteur: collaborator
• Regeneron Pharmaceuticals: collaborator
• MSD France: collaborator
• Alliance for International Medical Action: collaborator
• Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG): collaborator
• PACCI Program: collaborator

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

atoltivimab, maftivimab, and odesivimab-ebgn drug combination

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Marie JASPARD, PHD

  CORAL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie JASPARD, PHD

CONTACT

0658809012; marie.jaspard@aphp.fr

Béatrice SERRA, Master

CONTACT

beatrice.serra@coral.alima.ngo

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 21, 2022
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share