Ebola Virus Survivor Clinical Trial
Official title:
Tolerance and Activity Assessment of High Doses of Favipiravir in Male Survivors With Ebola Virus in the Semen
This study aims to evaluate favipiravir high dose tolerance in male survivor of Ebola Virus Disease (EVD) with Ebola Virus (EBOV) RNA in semen. This is a dose escalation study with 3 cohorts of 6 patients, each dose level including 2 sentinel patients.
Rational:
- Data suggesting persistence of EBOV in semen a few months after the end of EVD and
sexual transmission of EBOV
- Encouraging results on favipiravir efficacy to reduce mortality of EVD in JIKI trial
(NCT02329054 )
- Favipiravir trough plasma concentration in JIKI trial lower than predicted by population
pharmacokinetic model, suggesting an increase of dose might be necessary to achieve a
therapeutically relevant exposure.
Objectives:
- Primary objective: to assess clinical and biological tolerance of high-dosed favipiravir
bid for 14 days
- Secondary objectives: to assess the activity of favipiravir on evolution of EBOV RNA and
infectious loads in semen under treatment; the trough plasma and semen concentrations of
favipiravir; and genetic factors associated with favipiravir pharmacokinetic.
Dose escalation scheme:
Each patient of each cohort will receive favipiravir loading doses of 4800 mg at Day 1 (2400
mg bid), following by 3600 mg (1800 mg bid) from Day 2 to 14 (cohort 1), then 3600, 4200 or
4800 mg from Day 2 to 14 (cohort 2 and 3), depending on previous cohort results.
Escalation rules are based on the number of patient undergoing treatment-related adverse
events (TRAE) of grade 3 or 4 according to the Common Terminology Criteria for Adverse Events
v4.03 (CTCAE), as defined by the investigator and sponsor.
Participants will attend medical visits at Day 1, Day 3, Day 7, Day 10, Day 14, Day 21 and
clinical tolerance will be assessed daily by phone call from Day 1 to Day 14.
At the end of the first cohort:
- if no TRAE, cohort 2 will be given 2400 mg bid from Day 2 to 14;
- if 1 or 2 TRAE is observed, cohort 2 will be given 2100 mg bid from Day 2 to Day 14;
- if 3 or more TRAE is observed, cohort 2 will be given the same dose as cohort 1.
At the end of cohort 2, same rules will be apply to cohort 3, without exceed 4800 mg of
favipiravir per day.
Each cohort will include 6 patients. Each dose level will comprise 2 sentinel patients.
In their own interest, patients included in a cohort with detection of EBOV RNA in semen by
RT-PCR (CT<38) at Day 21, could be included in the next cohort.
Recruitment will start among PostEbogui cohort from coast Guinea.
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