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Clinical Trial
. 2016 Sep 9;11(9):e0162199.
doi: 10.1371/journal.pone.0162199. eCollection 2016.

Experimental Treatment of Ebola Virus Disease with Brincidofovir

Jake Dunning  1 , Stephen B Kennedy  2 , Annick Antierens  3 , John Whitehead  4 , Iza Ciglenecki  5 , Gail Carson  1 , Rupa Kanapathipillai  3 , Lyndsey Castle  1 , Rebecca Howell-Jones  1 , Raul Pardinaz-Solis  1 , Jennifer Grove  1 , Janet Scott  6 , Trudie Lang  1 , Piero Olliaro  1   7 , Peter W Horby  1 ; RAPIDE-BCV trial team
Affiliations
Clinical Trial

Experimental Treatment of Ebola Virus Disease with Brincidofovir

Jake Dunning et al. PLoS One. .

Abstract

Background: The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic.

Methods and findings: In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD.

Conclusions: Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients.

Trial registration: Pan African Clinical Trials Registry PACTR201411000939962.

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Conflict of interest statement

The authors have no reported conflicts of interest. PO is a staff member of the World Health Organization (WHO); the authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the WHO.

Figures

Fig 1
Fig 1. CONSORT Flow Diagram.
Consort diagram of patients eligible, recruited, numbers followed up and included in analysis.
See this image and copyright information in PMC

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