PREVAIL IV: A Randomized, Double-Blind, Two-Phase, Phase 2 Trial of Remdesivir versus Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors

Clin Infect Dis. 2021 Mar 12;ciab215. doi: 10.1093/cid/ciab215. Online ahead of print.

Abstract

Background: Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA.

Methods: We recruited men with persistent seminal Ebola RNA in Liberia and in Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over one hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) pre-enrollment semen tests. The study team was blinded to treatment group allocation and specific liver related lab results. We evaluated the difference in mean assay negativity rate (ANR), i.e., the proportion of negative tests for each participant in each group in the treatment (days 1-28) and follow-up (months 2-6) phases, on an intention-to-treat basis. ClinicalTrials.gov NCT02818582; closed.

Results: We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (sd=24%) and 76% (sd=30%) in the remdesivir and placebo arms, respectively (p=0.270). The mean follow-up phase ANRs were 96% (sd=10%) and 81% (sd=29%) in the remdesivir and placebo arms, respectively (p=0.041). The five-day remdesivir regimen was well-tolerated with no safety concerns.

Conclusions: In this small trial, remdesivir 100mg/day for five days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors two to six months after administration. A larger follow up study is necessary to confirm results.

Keywords: Ebola survivors; Ebola virus disease; controlled clinical trial; post-Ebola syndrome; remdesivir.

Associated data

  • ClinicalTrials.gov/NCT02818582