PREVAIL IV – a trial to investigate if GS-5734 eliminates Ebola virus from semen

PREVAIL IV, a trial for men who have survived Ebola virus disease (EVD) but continue to have evidence of Ebola RNA in their semen, has opened.

The six-month study will enrol 60 to 120 EVD survivors whose semen has evidence of Ebola virus RNA prior to their enrolment. Participants in the double-blind trial will receive either Gilead’s investigational drug GS-5734 or a placebo.

Liberia was one of the hardest hit countries during the Ebola epidemic of 2014-15. On June 9, the World Health Organisation declared the end of the most recent outbreak in Liberia and the country entered a 90-day period of heightened surveillance to ensure that any new cases are quickly identified and contained. “We know that traces of Ebola virus can sometimes remain in a recovered person’s body and can initiate a new bout of illness in the survivor or be passed onto others, which could start a new chain of infection in the community,” said National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, M.D. “The goal of the PREVAIL IV trial is to see if the experimental drug can eliminate the traces of Ebola virus from semen in men who have survived Ebola infection. It is anticipated that this would decrease the risk of passing the virus to their sexual partners. If so, the drug would be another weapon in our arsenal against Ebola virus disease.”

GS-5734 has been shown to reduce viremia in non-human primates

Upon enrolment, volunteers in the new trial will receive the study drug (or placebo) once a day for five days and will provide multiple blood and semen samples during this period. All volunteers must have previously enrolled in the PREVAIL III Ebola Natural History study for survivors and their household and sexual contacts. Prior to enrolment, volunteers will be tested for normal kidney and liver function. Volunteers will be seen at the clinic 10 times in the first month and then once a month for the remaining five months. Volunteers will provide blood and semen samples throughout the trial period. Investigators will test the semen samples to see if Ebola viral RNA can continue to be detected. All volunteers will be counselled to use condoms during the course of the trial.

GS-5734 has previously been tested for safety in healthy men and women. In that study, no serious side effects of the experimental drug were detected, but some volunteers experienced a rise and then a fall in liver enzyme levels. This information has been incorporated into the new trial by the study investigators, who will be monitoring volunteers for kidney and liver function during the trial. In non-human primates infected experimentally with a lethal dose of Ebola virus, GS-5734 has been shown to reduce viremia and to improve survival.

The trial is sponsored by NIAID in partnership with the Ministry of Health of Liberia and Gilead Sciences.