EBOla Post-Exposure Prophylaxis (EBO-PEP)

January 21, 2026 updated by: ANRS, Emerging Infectious Diseases

Evaluation of the Efficacy of a Post-exposure Prophylaxis (PEP) Strategy in Contacts at High Risk of Developing Ebola Virus Disease (EVD)

EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.

The trial will be open during EVD epidemics and will recruit asymptomatic participants at high risk of developing EVD.

Participants will be randomized (1:1) into one of two trial arms:

  • Arm 1 (ERV): Ervebo D0 (72 million PFU IM)
  • Arm 2 (ERV+IMZ): Ervebo D0 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D0 + Ervebo D56 (revaccination)

Definition of high-risk:

Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD

Trial follow-up All participants are monitored daily for a minimum of 21 days.

Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center:

  • at Day 5, Day 10, and Day 21 for the ERV arm,
  • at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team.

Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb.

Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants.

Follow-up in Case of Hospitalisation In case of clinical signs suggestive of EVD, participants enter the suspected case management pathway at the Ebola Treatment Center (ETC).

If EVD is confirmed by EBOV PCR, participants are allowed at the ETC, and their study samples are discontinued. They continue to be followed by the research team, and daily data are collected throughout their stay at the ETC until they are discharged alive or deceased. The day of discharge from the ETC marks the end of follow-up in the study for these participants.

Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.

Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.

If EVD is not confirmed, participants continue to be followed up by the PEP center according to the protocol.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Since its discovery in the Democratic Republic of Congo (DRC) in 1976, the EBOV virus has been responsible for numerous epidemics. Outbreaks have occurred in the DRC, Gabon, Guinea, Liberia and Sierra Leone. Imported cases were also discovered in 1996 in South Africa, and in 2014 in Mali, Nigeria, Senegal, Italy, Spain, UK and USA (1). To date, the largest EVD epidemic occurred in West Africa between 2014 and 2016. It was responsible for over 28,000 infections and more than 11,000 deaths (2-4). Since this epidemic, EVD has emerged and re-emerged regularly in Sub-Saharan Africa (SSA).

Post-exposure prophylaxis (PEP) is the treatment of people at high risk of EVD. The main aim of PEP is to intervene during the asymptomatic incubation period (2-21 days) to prevent the development of EVD.

In addition to preventing the disease in individuals, an effective PEP strategy could reduce the rate of secondary attacks, thus interrupting transmission chains. If introduced rapidly, this tool could halt the spread of the disease and contribute to the fight against EVD epidemics (5). The particular vulnerability of healthcare personnel has been highlighted during several outbreaks, due to their close contact with infected patients and contaminated equipment (6). With an effective and accessible PEP tool, it will be possible to ensure the safety and protection of these essential personnel and minimize the risk of nosocomial transmission within healthcare establishments. PEP could also benefit contact tracing efforts by providing an appropriate preventive measure. By integrating PEP into comprehensive epidemic response strategies, it will be possible to improve countries' ability to control and mitigate the public health impact of EVD epidemics and prevent future outbreaks.

There is currently no comprehensive PEP strategy, i.e. one that combines several interventions. Several prophylactic interventions have been evaluated, including vaccination and mAb immunotherapy, each with its advantages and limitations (7-9). Although not intended for this use, Ervebo vaccine is currently administered as PEP during EVD epidemics, by being administered to contacts regardless of exposure levels.

MAbs have been administered as PEP on a compassionate basis, to healthcare workers following occupational exposure, in line with WHO expert advice from 2018 (10). In addition, mAbs are recommended as PEP for newborns of Ebola-infected mothers, within seven days of birth (11). PEP can prevent the risk of infection associated with a particular contact, but not the persistent risk of infection during an epidemic. A comprehensive strategy to protect high-risk contacts must therefore be put in place, including both a drug to prevent EVD after contact (mAb or antiviral) and a vaccine for long-term immunity, to guarantee both immediate and prolonged protection.

Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralizing humanized mAbs directed against 3 EBOV GP epitopes (atoltiviMab, maftiviMab and odesiviMab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates whose mothers have EVD at the time of delivery. Inmazeb inhibits viral entry into the target cell (12). This mechanism of action makes Inmazeb a promising candidate for PEP (34,40-44). In phase 1, the optimal dose was set at 150 mg/kg as a single intravenous (IV) dose, with good tolerability, except for moderate side effects such as headache and myalgia in 30% and 10% of participants respectively. The longest half-life of the three antibodies was 27.3 days (21.7 and 23.3 for the other two antibodies). At 180 days, the residual concentration of each antibody (administered at 150 mg/kg) is less than 10 mg/l (13). In the PALM trial, overall mortality after a single 150 mg/kg dose was estimated at 33.5% (versus 51.3% in the ZMapp control arm). However, the effect of treatment is strongly influenced by viral load. In patients with a high viral load at inclusion (NP Ct < 22), mortality was 63.6% (versus 86.2% in the Zmapp subgroup), while in patients with a low viral load at inclusion (NP Ct > 22), mortality was 11.2% (versus 25.8% in the Zmapp subgroup) (14). Following the PALM trial, Inmazeb was approved by the FDA for the treatment of EVD in adults and children (15).

A study conducted during the 10éme EVD epidemic in the DRC evaluated PEP with mAbs as part of a compassionate program (Post-Exposure Prophylaxis Monitored Emergency Used for Unregistered Intervention - PEP MEURI). In this study, 23 vaccine-naïve high-risk contacts received mAbs (21 Ebanga and 2 Inmazeb) after a median delay of one day between contact and PEP. At D14, none of the participants were symptom-free and their PCR was negative (16).

EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.

The trial will be open during EVD epidemics, and will recruit asymptomatic participants at high risk of developing EVD. Participants will be randomized (1:1) into one of two trial arms:

  • Arm 1 (control arm): Ervebo D1 (72 million PFU IM)
  • Arm 2: Ervebo D1 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D1 + Ervebo D56 (revaccination)

Definition of high-risk:

Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Democratic Republic of the Congo
      • Kinshasa, Democratic Republic of the Congo
        • National Institute for Biomedical Research (INRB)
        • Contact:
  • Guinea
      • Conakry, Guinea
        • Guinea Centre for Research and Training in Infectious Diseases (CERFIG)
        • Contact:
  • Liberia
      • Monrovia, Liberia
        • National Public Health Institute of Liberia
        • Contact:
  • Sierra Leone
      • Freetown, Sierra Leone
        • University of Sierra Leone College of Medicine and Allied Health Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  • Last high-risk contact within the last 5 days
  • No sign or symptoms of EVD
  • Signed and dated informed consent from participants over the age of majority to participate in the trial or from a representative of parental authority for minor participants.

Non-inclusion criteria

  • History of vaccination with Ervebo or any other EVD vaccine within the last 5 years (self-reported by the participant)
  • History of confirmed EVD within the last 5 years (self-reported by the participant)
  • Hypersensitivity to any of the experimental medical products (IMP) or their excipients (self-reported by the participant)
  • Participation in another therapeutic or vaccine trial for EVD
  • Any other reason that, at the investigator's discretion, could compromise the participant's safety and cooperation in the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ervebo vaccine alone
Administration of Ervebo vaccine (72 million PFU IM) at day 1
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:
  • r-VSV-ZEBOV vaccine
Experimental: Ervebo + Inmazeb
Administration of Ervebo vaccine (72 million PFU IM) and Inmazeb IV (150 mg/kg) at day 1 and Inmazeb IV (150 mg/kg) at day 56
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:
  • r-VSV-ZEBOV vaccine
Biological: Inmazeb
Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralising humanised mAbs directed against 3 epitopes of the EBOV GP (atoltivimab, maftivimab and odesivimab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates born to mothers with confirmed EVD.
Other Names:
  • REGN-EB3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
Time Frame: Between Day 1 and Day 21
EVD rate
Between Day 1 and Day 21

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerance
Time Frame: Between Day 1 and Day 60
Proportion of participants with a grade 3 or higher Adverse Event
Between Day 1 and Day 60
Severity of EVD
Time Frame: Between Day 1 and Day 60

Proportion of participants admitted to the Ebola Treatment Center with confirmed EVD meeting at least one of the following criteria:

  • Nucleoprotein cycle threshold (NP Ct) < 22
  • KDIGO stage 3
  • ASAT or ALAT > 5N
  • External bleeding
  • AVPU score
  • NEWS2 score ≥ 7
Between Day 1 and Day 60
Proportion of deaths
Time Frame: Between Day 1 and Day 60
Proportion of participants who died (all causes combined)
Between Day 1 and Day 60
Changes in viral load
Time Frame: Between Day 1 and Day 21
NP Ct curve (nucleoprotein cycle threshold)
Between Day 1 and Day 21
Estimating cost-effectiveness
Time Frame: Between Day 1 and up to Day 60
Incremental cost-effectiveness ratio (ICER) for ERV+IMZ arm vs ERV
Between Day 1 and up to Day 60
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
Time Frame: Between Day 1 and Day 60
EVD rate
Between Day 1 and Day 60
Proportion of participants with asymptomatic EVD
Time Frame: Between Day 1 and Day 21
Rate of PCR-confirmed EVD
Between Day 1 and Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

University of Bordeaux
Cheikh Anta Diop University, Senegal
Barcelona Institute for Global Health
Medecins Sans Frontieres, Netherlands
Alliance for International Medical Action
PACCI Program
Agence Nationale de Sécurité Sanitaire de Guinée (ANSS)
INSERM UMR S 1136
National Public Health Institute of Liberia
Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG)
National Institute for Biomedical Research DRC
The PANdemic preparedness plaTform for Health and Emerging infectious Response
University of Sierra Leone College of Medicine and Allied Health Sciences

Investigators

  • Study Chair: Placide MBALA, MD, MSPH, PhD, INRB

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

January 28, 2025

First Submitted That Met QC Criteria

February 18, 2025

First Posted (Actual)

February 24, 2025

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 0515s EBO-PEP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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