Experimental Treatment of Ebola Virus Disease with Brincidofovir.
<h4>Background</h4>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 age...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162199&type=printable |
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| author | Jake Dunning Stephen B Kennedy Annick Antierens John Whitehead Iza Ciglenecki Gail Carson Rupa Kanapathipillai Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Jennifer Grove Janet Scott Trudie Lang Piero Olliaro Peter W Horby RAPIDE-BCV trial team |
| author_facet | Jake Dunning Stephen B Kennedy Annick Antierens John Whitehead Iza Ciglenecki Gail Carson Rupa Kanapathipillai Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Jennifer Grove Janet Scott Trudie Lang Piero Olliaro Peter W Horby RAPIDE-BCV trial team |
| author_sort | Jake Dunning |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>Pan African Clinical Trials Registry PACTR201411000939962. |
| format | Article |
| id | doaj-art-60c087d0d1b1410393a2f7dcb96ebb68 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-60c087d0d1b1410393a2f7dcb96ebb682025-08-20T02:03:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016219910.1371/journal.pone.0162199Experimental Treatment of Ebola Virus Disease with Brincidofovir.Jake DunningStephen B KennedyAnnick AntierensJohn WhiteheadIza CigleneckiGail CarsonRupa KanapathipillaiLyndsey CastleRebecca Howell-JonesRaul Pardinaz-SolisJennifer GroveJanet ScottTrudie LangPiero OlliaroPeter W HorbyRAPIDE-BCV trial team<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>Pan African Clinical Trials Registry PACTR201411000939962.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162199&type=printable |
| spellingShingle | Jake Dunning Stephen B Kennedy Annick Antierens John Whitehead Iza Ciglenecki Gail Carson Rupa Kanapathipillai Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Jennifer Grove Janet Scott Trudie Lang Piero Olliaro Peter W Horby RAPIDE-BCV trial team Experimental Treatment of Ebola Virus Disease with Brincidofovir. PLoS ONE |
| title | Experimental Treatment of Ebola Virus Disease with Brincidofovir. |
| title_full | Experimental Treatment of Ebola Virus Disease with Brincidofovir. |
| title_fullStr | Experimental Treatment of Ebola Virus Disease with Brincidofovir. |
| title_full_unstemmed | Experimental Treatment of Ebola Virus Disease with Brincidofovir. |
| title_short | Experimental Treatment of Ebola Virus Disease with Brincidofovir. |
| title_sort | experimental treatment of ebola virus disease with brincidofovir |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0162199&type=printable |
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