Efficacy of Favipiravir Against Ebola (JIKI)

NCT02329054 | Completed Phase 2 DMC

• 1 other identifier: C14-63
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 4

Brief Summary

There is no specific treatment for Ebola Virus Disease (EVD). Current EVD care are supportive, and includes intravenous or oral rehydration, nutrition, pain killers, treatment of coinfections with antibacterial and antimalarial drugs, and blood transfusion when appropriate. Despite these interventions, mortality remains high since the ongoing Ebola outbreak in West Africa was declared in April. Potential anti-Ebola specific interventions include convalescent plasma, monoclonal and polyclonal antibodies, small inhibitory RNA (siRNA), synthetic adenosine analogues or RNA polymerase inhibitors. All these interventions are considered investigational due to lack of data in humans with EVD. In this study, the investigators chose to study the efficacy of favipiravir because this drug:

• showed anti-Ebola efficacy in immunodeficient murine models;
• has been studied in thousands of adult humans participating in anti-influenza trials, with good tolerance; it has been approved for treating novel or resistant influenza infections in Japan;
• is immediately available;
• can be used orally, and can be easily given in both adults and children because pills can be crushed and mixed in food or liquids;
• has recently been used in Europe for treating several patients with EVD; the French drug safety agency (ANSM) has reviewed published data as well as data provided by the firm (Toyama Chemical Co., Ltd), and approved its compassionate use in EVD. Here the investigators propose to assess the efficacy of high-dosed favipiravir in reducing mortality in humans with EVD. In the present trial "JIKI" (means "Hope" in "Kissi" language), investigators, sponsor, scientific advisory board and safety monitoring board will be coordinated in a very reactive way, so that any new fact can be discussed rapidly and the research plan can be adapted accordingly (change in drug dosage; use of drug combination; combination with another strategy such as passive immunization with convalescent plasma, etc.).

Conditions

Ebola Virus Disease

Keywords

Ebola Virus Disease; Antivirals; Mortality; Viral load; Proof-of-concept; Phase II trial; Guinea; Adults; Children

Outcome Measures

Primary Outcomes (1)

• Mortality

  Day-0 is the day of the first dose of favipiravir

  Day-14

Secondary Outcomes (6)

• Evolution of EBOV plasma RNA and infectious loads

  routine care venepuncture (Day-0; end of symptoms (EOS)+72h and EOS+96h if EOS >Day-9; or Day-12 and Day-13 if EOS <Day-9); (ii) additional trial venepuncture at: Day-2, Day-4 and Day-30 in group A1; Day-2 and Day-30 in group A2

• Occurrence of grade 3 or 4 clinical or biological adverse events (Common Terminology Criteria for Adverse Events, CTAE, v3.0)

  participants will be followed for the duration of hospital stay up to Day-14

• Evolution of viral micro-diversity of EBOV (including potential resistance mutations)

  routine care venepuncture (Day-0; end of symptoms (EOS)+72h and EOS+96h if EOS >Day-9; or Day-12 and Day-13 if EOS <Day-9); (ii) additional trial venepuncture at: Day-2, Day-4 and Day-30 in group A1; Day-2 and Day-30 in group A2

• Plasma trough concentrations of favipiravir

  routine care venepuncture (Day-0; end of symptoms (EOS)+72h and EOS+96h if EOS >Day-9; or Day-12 and Day-13 if EOS <Day-9); (ii) additional trial venepuncture at: Day-2, Day-4 and Day-30 in group A1; Day-2 and Day-30 in group A2

• Criteria for cure

  Day-30

Study Arms (1)

Favipiravir

EXPERIMENTAL

Favipiravir (oral administration, 200 mg light yellow, round-shaped, coated divisible tablets that can be crushed and mixed with liquid)

Drug: Favipiravir

Interventions

Favipiravir DRUG

Group A1: Day-0 (inclusion), h0: 2400 mg; h8: 2400 mg; h16: 1200 mg. Day-1 to Day-9: 1200 mg bid. Group A2: Day-0 (inclusion), h0: 2400 mg; h8: 2400 mg; h16: 1200 mg. Day-1 to Day-9: 1200 mg bid. Group C: daily dosages will be adapted to their body weight.

Also known as: AVIGAN

Favipiravir

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• age \>1 year and weighting ≥10kg,
• EVD confirmed by a positive qualitative PCR test,
• signed informed consent (signed by the parents/adults guardians in case of minor patient).
• pregnancy\*,
• inability to take the drug (encephalopathy, severe vomiting). \* Emergency use of favipiravir in pregnant women outside of the trial is envisaged and under evaluation.
• In this protocol, the investigators will refer to the following groups according to age and duration of symptoms\*\*:
• Group A1: adults with time between first symptoms and first dose of favipiravir ≤72h;
• Group A2: adults with time between first symptoms and first dose of favipiravir \>72h;
• Group C: all children \>1 year and weighting ≥10kg. Time of first symptom refers to the time of the beginning of any symptom considered to be related to EVD. \*\*Symptoms to be considered will be: acute onset of fever, severe headache, myalgia, extreme fatigue, vomiting, diarrhoea, abdominal pain, or unexplained hemorrhage.
• The division in groups is a matter of analysis, and will not be perceptible by the patients during the trial process. Patients in the three groups will receive the same treatment and will be followed under the same procedures, with only two exceptions: the number of additional blood sample collections will be lower in group A2 and C (n=2) than in group A1 (n=3) and daily dosages will be adapted to the body weight in group C.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (4)

The caregivers treatment center

Conakry, Guinea

Location

MSF Ebola treatment centre

Gueckedou, Guinea

Location

French Red Cross Ebola care center

Macenta, Guinea

Location

ALIMA Ebola care center

Nzérékoré, Guinea

Location

Related Publications (5)

• Mentre F, Taburet AM, Guedj J, Anglaret X, Keita S, de Lamballerie X, Malvy D. Dose regimen of favipiravir for Ebola virus disease. Lancet Infect Dis. 2015 Feb;15(2):150-1. doi: 10.1016/S1473-3099(14)71047-3. Epub 2014 Nov 28. No abstract available.

  PMID: 25435054 BACKGROUND

• Nguyen TH, Guedj J, Anglaret X, Laouenan C, Madelain V, Taburet AM, Baize S, Sissoko D, Pastorino B, Rodallec A, Piorkowski G, Carazo S, Conde MN, Gala JL, Bore JA, Carbonnelle C, Jacquot F, Raoul H, Malvy D, de Lamballerie X, Mentre F; JIKI study group. Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted. PLoS Negl Trop Dis. 2017 Feb 23;11(2):e0005389. doi: 10.1371/journal.pntd.0005389. eCollection 2017 Feb.

  PMID: 28231247 RESULT

• 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.

  PMID: 35127447 RESULT

• Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH, Baize S, Camara AM, Maes P, Shepherd S, Danel C, Carazo S, Conde MN, Gala JL, Colin G, Savini H, Bore JA, Le Marcis F, Koundouno FR, Petitjean F, Lamah MC, Diederich S, Tounkara A, Poelart G, Berbain E, Dindart JM, Duraffour S, Lefevre A, Leno T, Peyrouset O, Irenge L, Bangoura N, Palich R, Hinzmann J, Kraus A, Barry TS, Berette S, Bongono A, Camara MS, Munoz VC, Doumbouya L, Harouna S, Kighoma PM, Koundouno FR, Lolamou R, Loua CM, Massala V, Moumouni K, Provost C, Samake N, Sekou C, Soumah A, Arnould I, Komano MS, Gustin L, Berutto C, Camara D, Camara FS, Colpaert J, Delamou L, Jansson L, Kourouma E, Loua M, Malme K, Manfrin E, Maomou A, Milinouno A, Ombelet S, Sidiboun AY, Verreckt I, Yombouno P, Bocquin A, Carbonnelle C, Carmoi T, Frange P, Mely S, Nguyen VK, Pannetier D, Taburet AM, Treluyer JM, Kolie J, Moh R, Gonzalez MC, Kuisma E, Liedigk B, Ngabo D, Rudolf M, Thom R, Kerber R, Gabriel M, Di Caro A, Wolfel R, Badir J, Bentahir M, Deccache Y, Dumont C, Durant JF, El Bakkouri K, Uwamahoro MG, Smits B, Toufik N, Van Cauwenberghe S, Ezzedine K, D'Ortenzio E, Pizarro L, Etienne A, Guedj J, Fizet A, de Sainte Fare EB, Murgue B, Tran-Minh T, Rapp C, Piguet P, Poncin M, Draguez B, Duverger TA, Barbe S, Baret G, Defourny I, Carroll M, Raoul H, Augier A, Eholie SP, Yazdanpanah Y, Levy-Marchal C, Antierrens A, Van Herp M, Gunther S, de Lamballerie X, Keita S, Mentre F, Anglaret X, Malvy D; JIKI Study Group. Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med. 2016 Apr 5;13(4):e1002009. doi: 10.1371/journal.pmed.1002009. eCollection 2016 Apr.

  PMID: 27046271 RESULT

• Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH, Baize S, Camara AM, Maes P, Shepherd S, Danel C, Carazo S, Conde MN, Gala JL, Colin G, Savini H, Bore JA, Le Marcis F, Koundouno FR, Petitjean F, Lamah MC, Diederich S, Tounkara A, Poelart G, Berbain E, Dindart JM, Duraffour S, Lefevre A, Leno T, Peyrouset O, Irenge L, Bangoura N, Palich R, Hinzmann J, Kraus A, Barry TS, Berette S, Bongono A, Camara MS, Chanfreau Munoz V, Doumbouya L, Souley Harouna, Kighoma PM, Koundouno FR, Rene Lolamou, Loua CM, Massala V, Moumouni K, Provost C, Samake N, Sekou C, Soumah A, Arnould I, Komano MS, Gustin L, Berutto C, Camara D, Camara FS, Colpaert J, Delamou L, Jansson L, Kourouma E, Loua M, Malme K, Manfrin E, Maomou A, Milinouno A, Ombelet S, Sidiboun AY, Verreckt I, Yombouno P, Bocquin A, Carbonnelle C, Carmoi T, Frange P, Mely S, Nguyen VK, Pannetier D, Taburet AM, Treluyer JM, Kolie J, Moh R, Gonzalez MC, Kuisma E, Liedigk B, Ngabo D, Rudolf M, Thom R, Kerber R, Gabriel M, Di Caro A, Wolfel R, Badir J, Bentahir M, Deccache Y, Dumont C, Durant JF, El Bakkouri K, Gasasira Uwamahoro M, Smits B, Toufik N, Van Cauwenberghe S, Ezzedine K, D'Ortenzio E, Pizarro L, Etienne A, Guedj J, Fizet A, Barte de Sainte Fare E, Murgue B, Tran-Minh T, Rapp C, Piguet P, Poncin M, Draguez B, Allaford Duverger T, Barbe S, Baret G, Defourny I, Carroll M, Raoul H, Augier A, Eholie SP, Yazdanpanah Y, Levy-Marchal C, Antierrens A, Van Herp M, Gunther S, de Lamballerie X, Keita S, Mentre F, Anglaret X, Malvy D; JIKI Study Group. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med. 2016 Mar 1;13(3):e1001967. doi: 10.1371/journal.pmed.1001967. eCollection 2016 Mar.

  PMID: 26930627 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

favipiravir

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Denis Malvy, Professor

  CHU de Bordeaux & INSERM, Université de Bordeaux, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2014
• First Posted: December 31, 2014
• Study Start: December 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 18, 2025

Record last verified: 2015-03

Locations

GU (4)