Ebola Virus SurvivorPhase 2FORCENCT02739477
Tolerance and Activity Evaluation of High Doses of Favipiravir Against Ebola Virus in the Semen
A Phase 2 study testing Favipiravir in people with Ebola Virus Survivor, run by Institut National de la Santé Et de la Recherche Médicale, France at 2 sites in Guinea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Ebola Virus Survivor
- What is being tested?
- Favipiravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesGuinea
- Study dates
- Apr 2016to Aug 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male survivor of biologically confirmed EVD
- age >= 18 years
- EBOV RT-PCR on semen with cycle threshold [Ct]<38 at Day -7 and semen aliquot available for later quantification of EBOV
- signed informed consent
- Non-Inclusion Criteria:
- EBOV RT-PCR on blood with cycle threshold [Ct]<38 at Day -7
Show all 14Show fewer
- Biological abnormality higher than grade 2 according to CTCAE (v4.03) on following parameters: creatinine, ASAT, ALAT, alkaline phosphatase, total bilirubin
- Fridericia corrected QT interval (QTc) > 450 ms
- Concomitant use of QT/QTc interval-prolonging drugs or drugs that could cause electrolyte imbalance, such as: loop diuretics, thiazide diuretics or related
- Previous gout attack or ongoing treatment for gout or hyperuricemia
- Ongoing pyrazinamide treatment or other drug known to induce hyperuricemia
- Previous hypersensitivity reaction due to nucleoside analogue
- Symptom or biological value suggesting systemic disorder (renal, hepatic, cardio-vascular, pulmonary) or any medical condition that could interfere with results interpretation or compromise participants' health
- Explicit refusal to comply with proper use of drug (condom use)
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
About this study
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.
Read the detailed description
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.
- Conditions
- Ebola Virus Survivor
- Being tested
- Favipiravir
- Keywords
- Favipiravir, Tolerance, Survivor, Ebola Virus, Genital reservoir, Guinea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FavipiravirDrug
Also called AVIGAN
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.
| Study group | Role | What they receive |
|---|---|---|
| Favipiravir | Experimental | Favipiravir (oral administration, 200 mg light yellow, round-shaped, coated divisible tablets that can be crushed and mixed with liquid) Receives: Drug: Favipiravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Day 1 is the first day of favipiravir intake
Measured: Day 14
Secondary outcomes (3)
Evolution of EBOV semen RNA and infectious loads
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.
Measured: Semen collection will be performed at least at Day 7, Day 14, Day 21 and Day 90
Plasma and semen trough concentrations of favipiravir
Measured: 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
Measured: Blood collection at Day 1 will be used for further genotyping.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionAug 2016
- Study completionAug 2016
Why it stopped: End date of epidemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ebola Virus SurvivorStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Daouda Sissoko, Doctor, Principal investigator, Inserm 897 unit, ISPED, Université de Bordeaux, Bordeaux cedex
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02739477
- Sponsor's protocol ID
- C15-101
- Acronym
- FORCE
- Status last verified
- Feb 2025
- First submitted
- 24 Feb 2016
- Last updated
- 24 Feb 2025
- Results posted
- No
Publications
Eloy P, Laouenan C, Beavogui AH, Keita S, Manchon P, Etard JF, Sissoko D, Mentre F, Malvy D. High doses of favipiravir in two men survivors of Ebola virus disease carrying Ebola virus in semen in Guinea. IDCases. 2022 Jan 21;27:e01412. doi: 10.1016/j.idcr.2022.e01412. eCollection 2022.
PubMed 35127447
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolerance and Activity Assessment of High Doses of Favipiravir in Male Survivors With Ebola Virus in the Semen
- ClinicalTrials.gov ID
- NCT02739477
- Acronym / sponsor ID
- FORCE / C15-101
- Conditions
- Ebola Virus Survivor
- Keywords
- Favipiravir, Tolerance, Survivor, Ebola Virus, Genital reservoir, Guinea
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End date of epidemic
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Apr 2016
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Favipiravir | Experimental | Drug: FavipiravirFavipiravir (oral administration, 200 mg light yellow, round-shaped, coated divisible tablets that can be crushed and mixed with liquid) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- male survivor of biologically confirmed EVD
- age >= 18 years
- EBOV RT-PCR on semen with cycle threshold [Ct]<38 at Day -7 and semen aliquot available for later quantification of EBOV
- signed informed consent
- EBOV RT-PCR on blood with cycle threshold [Ct]<38 at Day -7
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FavipiravirAlso: AVIGANCohort 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. | Drug | Favipiravir |
Primary outcome
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
3 secondary outcomes
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
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.
Results and safety
The study was stopped early (reason given: End date of epidemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Results publication: PubMed 35127447Eloy P, Laouenan C, Beavogui AH, Keita S, Manchon P, Etard JF, Sissoko D, Mentre F, Malvy D. High doses of favipiravir in two men survivors of Ebola virus disease carrying Ebola virus in semen in Guinea. IDCases. 2022 Jan 21;27:e01412. doi: 10.1016/j.idcr.2022.e01412. eCollection 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daouda Sissoko, Doctor principal investigator
Inserm 897 unit, ISPED, Université de Bordeaux, Bordeaux cedex
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Favipiravir in people with Ebola Virus Survivor, run by Institut National de la Santé Et de la Recherche Médicale, France at 2 sites in Guinea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: End date of epidemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02739477, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.