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

Dunning, Jake and Sahr, Foday and Rojek, Amanda and Gannon, Fiona and Carson, Gail and Idriss, Baimba and Massaquoi, Thomas and Gandi, Regina and Joseph, Sebatu and Osman, Hassan K. and Brooks, Timothy J. G. and Simpson, Andrew J. H. and Goodfellow, Ian G and Thorne, Lucy and Arias, Armando and Merson, Laura and Castle, Lyndsey and Howell-Jones, Rebecca and Pardinaz-Solis, Raul and Hope-Gill, Benjamin and Ferri, Mauricio and Grove, Jennifer and Kowalski, Mark and Stepniewska, Kasia and Lang, Trudie and Whitehead, John Raymond and Olliaro, Piero and Samai, Mohammed and Horby, Peter W. (2016) Experimental treatment of Ebola virus disease with TKM-130803:a single-arm phase 2 clinical trial. PLoS Medicine, 13 (4). ISSN 1549-1277

Full text not available from this repository.

Abstract

Background: TKM-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 Findings: In 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 infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions: Administration 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. Trial registration: Pan African Clinical Trials Registry PACTR201501000997429 © 2016 Dunning et al.

Item Type:
Journal Article
Journal or Publication Title:
PLoS Medicine
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700
Subjects:
ID Code:
79738
Deposited By:
Deposited On:
24 May 2016 14:30
Refereed?:
Yes
Published?:
Published
Last Modified:
26 May 2020 04:56