Back to Search Start Over

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques

Authors :
Elizabeth E. Zumbrun
Carly B. Garvey
Jay B. Wells
Ginger C. Lynn
Sean A. Van Tongeren
Jesse T. Steffens
Kelly S. Wetzel
Darrell L. Wetzel
Heather L. Esham
Nicole L. Garza
Eric D. Lee
Jennifer L. Scruggs
Franco D. Rossi
Elizabeth S. Brown
Jessica M. Weidner
Laura M. Gomba
Kristan A. O’Brien
Alexandra N. Jay
Xiankun Zeng
Kristen S. Akers
Paul A. Kallgren
Ethan Englund
J. Matthew Meinig
Jeffrey R. Kugelman
Joshua L. Moore
Holly A. Bloomfield
Sarah L. Norris
Tameka Bryan
Christie H. Scheuerell
Jesse Walters
Nevena Mollova
Christiana Blair
Darius Babusis
Tomas Cihlar
Danielle P. Porter
Bali Singh
Charlotte Hedskog
Sina Bavari
Travis K. Warren
Roy Bannister
Source :
Viruses, Vol 16, Iss 12, p 1934 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical–pathological changes associated with EBOV disease in this model.

Details

Language :
English
ISSN :
19994915
Volume :
16
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.243a58d11234ef6905715ea28ce6153
Document Type :
article
Full Text :
https://doi.org/10.3390/v16121934