INRB-ANRS 0515s EBO-PEP

Objectives of EBO-PEP

EBO-PEP is a randomised, controlled platform trial. It aims to evaluate different post-exposure prophylaxis strategies among contacts of FVD cases during a specific outbreak. Treatment comparisons may utilise flexible methodologies and are described in sub-protocols appended to a master protocol. Each sub-protocol is named according to the investigational medicinal product (IMP) concerned and the target viral species.

Participants are individually randomised into different intervention arms depending on the virus and the options available for post-exposure prophylaxis (PEP) during a specific outbreak. The total duration of follow-up for trial participants is 42 days or until the end of hospitalisation in an Ebola Treatment Centre (ETC) for confirmed cases of filovirus disease. All participants are monitored daily for at least 21 days.

Primary objective

• To conduct a phase III, multicentre, multi-outbreak clinical trial to test the efficacy of different interventions used in PEP for high-risk contacts of filovirus diseases.

Secondary objectives

• To strengthen the capacity of clinical researchers and increase community knowledge and engagement in filovirus research.
• To promote the adoption of the PEP strategy for high–risk contacts through strategic communication and targeted advocacy with key stakeholders

First two sub-protocols

Sub–protocol No. 1: EBO–PEP ODV–BDBV

The investigational medicinal product proposed for the evaluation of PEP against the Ebola Bundibugyo virus is obeldesivir (EBO–PEP ODV–BDBV sub–protocol).

The EBO-PEP ODV-BDBV sub-protocol provides the framework for a double-blind, placebo-controlled superiority trial with two parallel arms, designed to assess the safety and efficacy of obeldesivir (ODV) compared with placebo in the prevention of symptomatic Ebola virus disease (EVD) caused by infection with the Bundibugyo virus (BVD) in participants who have had high-risk contact.

Participants will be individually randomised in a 1:1 ratio between the following two arms:

• Placebo
• Obeldesivir (ODV)

An interim analysis is planned at the halfway point of recruitment in order to:

• assess the efficacy of the treatment at an early stage;
• assess whether the trial is futile;
• and, if necessary, reassess the required sample size.

Inclusion criteria:

• Documented contact with a confirmed case of FVD (risk level defined in each sub-protocol)
• No signs or symptoms of FVD
• Informed consent signed and dated by adult participants to take part in the trial, or by a legal representative for minors or adults with cognitive impairment

Number of participants:

• 494 participants per arm
• Total sample size of 998 participants

Sub-protocol No. 2: EBO-PEP RDV-BDBV

The EBO-PEP RDV-BDBV sub-protocol governs a prospective interventional cohort study evaluating the administration of remdesivir for the prevention of symptomatic Bundibugyo Ebola virus disease (BVD) in children, as well as in pregnant and breastfeeding women who have had high-risk contact.

The cohort is being conducted in parallel with the EBO-PEP ODV-BDBV sub-protocol and focuses on the population most vulnerable to Ebola virus disease.

Inclusion criteria specific to sub-protocol 2:

• Age < 12 years.
• Pregnant women or those with a positive pregnancy test.
• Women planning to breastfeed for the duration of the study and up to 21 days after the last dose of the study intervention.
• Most recent high-risk contact within the last 5 days with a case of Ebola virus disease caused by the Bundibugyo virus (BDBV)

Number of participants: 350

Definition of high-risk contact

• Direct contact with a person with EVD confirmed by PCR presenting with diarrhoea, vomiting or external haemorrhages (‘wet symptoms’), or with their bodily fluids;
• Direct contact with the corpse of a person with confirmed or probable EVD;
• Injection with a syringe contaminated by a person with confirmed or probable EVD.