Tolerance and Activity Evaluation of High Doses of Favipiravir Against Ebola Virus in the Semen (FORCE)
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|ClinicalTrials.gov Identifier: NCT02739477|
Recruitment Status : Unknown
Verified May 2016 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was: Recruiting
First Posted : April 15, 2016
Last Update Posted : May 4, 2016
|Condition or disease||Intervention/treatment||Phase|
|Ebola Virus Survivor||Drug: Favipiravir||Phase 2|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tolerance and Activity Assessment of High Doses of Favipiravir in Male Survivors With Ebola Virus in the Semen|
|Study Start Date :||April 2016|
|Estimated Primary Completion Date :||August 2016|
Favipiravir (oral administration, 200 mg light yellow, round-shaped, coated divisible tablets that can be crushed and mixed with liquid)
Cohort 1: Day 1 (inclusion) 4800 mg (2400 mg bid). Day 2 to Day 14: 3600 mg (1800 mg bid).
Cohort 2: Day 1 (inclusion) 4800 mg (2400 mg bid). Day 2 to Day 14: 3600, 4200, 4800 mg per day depending on cohort 1 results.
Cohort 3: Day 1 (inclusion) 4800 mg (2400 mg bid). Day 2 to Day 14: 3600, 4200, 4800 mg per day depending on cohorts 1 and 2 results.
Other Name: AVIGAN
- Number of patients undergoing grade 3 or 4 clinical or biological adverse events related to Favipiravir (Common Terminology Criteria for Adverse Events, CTCAE, v4.03) [ Time Frame: Day 14 ]Day 1 is the first day of favipiravir intake
- Evolution of EBOV semen RNA and infectious loads [ Time Frame: Semen collection will be performed at least at Day 7, Day 14, Day 21 and Day 90 ]From Day 14 to Day 90, semen EBOV PCR will be performed every 3 weeks until their semen tests negative for virus twice by RT-PCR, with an interval of one week between tests.
- Plasma and semen trough concentrations of favipiravir [ Time Frame: Plasma collection at Day 3, Day7, Day 10 and Day 14. Semen collection at Day 7 and Day 14 ]
- Genetic variations associated with favipiravir exposition [ Time Frame: Blood collection at Day 1 will be used for further genotyping. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02739477
|Contact: Daouda Sissoko, Doctor||00224 654 77 88 email@example.com|
|Contact: Sakoba Keita, Doctor||+224 622 931 firstname.lastname@example.org|
|Contact: Daouda Sissoko, Doctor|
|Contact: Daouda Sissoko, Doctor|
|Principal Investigator:||Daouda Sissoko, Doctor||Inserm 897 unit, ISPED, Université de Bordeaux, Bordeaux cedex|