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Reference: Dunning, J, Sahr, F, Rojek, A et al., (2016). Experimental treatment of Ebola virus disease with TKM-130803: A single-arm phase 2 clinical trial. PLoS Medicine, 13 (4), e1001997.Citable link to this page:

 

Experimental treatment of Ebola virus disease with TKM-130803: A single-arm phase 2 clinical trial.

Abstract: BackgroundTKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated.Methods and FindingsIn this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission.After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM- 130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusionrelated reaction observed. Three patients were enrolled in the observational cohort, of whom two died.ConclusionsAdministration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2016-03-08 Funder: Wellcome Trust   Funder: Seventh Framework Programme   Funder: Department for International Development   Notes:© 2016 Dunning et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org/

Journal: PLoS Medicinesee more from them

Publication Website: http://journals.plos.org/plosmedicine/

Volume: 13

Issue: 4

Issue Date: 2016-04

pages:e1001997Identifiers

Doi: https://doi.org/10.1371/journal.pmed.1001997

Issn: 1549-1676

Issn: 1549-1277

Uuid: uuid:4b9f83ce-449a-479d-9230-f6aaf978e553

Urn: uri:4b9f83ce-449a-479d-9230-f6aaf978e553

Pubs-id: pubs:616748 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: RAPIDE-TKM trial team Humans Hemorrhagic Fever, Ebola RNA, Small Interfering RNA, Viral Antiviral Agents Treatment Outcome Viral Load Infusions, Intravenous Survival Analysis Time Factors Adult Aged Aged, 80 and over Middle Aged Sierra Leone Female Male Ebolavirus Nanoparticles Host-Pathogen Interactions Young Adult RNAi Therapeutics

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Author: Dunning, J - Oxford, MSD, NDM, Tropical Medicine - - - Sahr, F - - - Rojek, A - Oxford, MSD, NDM, NDM Experimental Medicine - - -

Source: https://ora.ox.ac.uk/objects/uuid:4b9f83ce-449a-479d-9230-f6aaf978e553



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