Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Drugs for Neglected Diseases
Sponsor:
Information provided by (Responsible Party):
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT01685827
First received: September 12, 2012
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

This clinical trial is designed to prove the efficacy and safety of Fexinidazole as an oral treatment for human african trypanosomiasis in advanced stage. The Fexinidazole is compared to reference treatment NECT. The trial will try to demonstrate that Fexinidazole is not inferior to NECT treatment.


Condition Intervention Phase
Human African Trypanosomiasis
Sleeping Sickness
Drug: Fexinidazole
Drug: Nifurtimox
Drug: Eflornithine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Fexinidazole Compared to Nifurtimox-Eflornithine Combination Therapy (NECT) in Patients With Late-stage Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: Pivotal, Non-inferiority, Multicentre, Randomised, Open-label Study

Resource links provided by NLM:


Further study details as provided by Drugs for Neglected Diseases:

Primary Outcome Measures:
  • success or failure at 18 months FU visit [ Time Frame: 18 months after treatment ] [ Designated as safety issue: No ]

    The primary endpoint is the outcome (success or failure) at the test of cure (ToC) visit 18 months after the end of treatment (EOT) adapted from WHO criteria.

    Success at 18 months is:

    • Either cure:

      • patient alive,
      • AND with no evidence of trypanosomes in any body fluid,
      • AND 20 or less WBC/µl CSF
    • Or Probable cure:

      • Patient with no parasitological evidence of relapse in blood and lymph
      • AND who refuses lumbar puncture OR whose CSF sample is haemorrhagic without trypanosomes
      • AND whose clinical condition is satisfactory (without clinical symptom or signs) OR whose clinical status is unlikely to be due to HAT


Secondary Outcome Measures:
  • Safety endpoint [ Time Frame: 18 days - observation period ] [ Designated as safety issue: Yes ]

    Occurrence of any grade (all grades combined) adverse events during the observation period (D1-18) including:

    • any worsening of clinical symptoms listed in the inclusion checklist of symptoms and signs,
    • laboratory abnormalities of grade ≥ 2
    • Occurrence of grade ≥ 3 adverse events during the observation period
    • Occurrence of drug-related adverse events (grade ≥ 3 and any grade) during the observation period

  • Safety endpoint [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Occurrence of any serious adverse events from first drug intake to the end of follow-up period (18 months), and from M18 to M24.

  • Pharmacokinetics endpoint [ Time Frame: from D8 to D12 after first dosing ] [ Designated as safety issue: No ]
    Whole blood and CSF concentrations of fexinidazole, M1, M2 and PK parameters derived from a model of population PK data.

  • QT evaluation [ Time Frame: D0 - D4 - D10 ] [ Designated as safety issue: Yes ]
    recording of triplicates ECG


Estimated Enrollment: 510
Study Start Date: October 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NECT (Nifurtimox Eflornithine Combination Therapy)
  • Nifurtimox tablets will be given orally three times a day, at the daily dose of 15 mg/kg/day, for 10 days.
  • Eflornithine (400 mg/kg/day) will be given twice daily for 7 days, as a 2-hour IV infusion.
Drug: Nifurtimox
Other Name: Lampit
Drug: Eflornithine
Other Name: Ornidyl
Experimental: Fexinidazole

Fexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of:

  • 1 800 mg (3 tablets) once a day for 4 days,
  • Followed by 1 200 mg (2 tablets) once a day for 6 days. Total duration of treatment will be 10 days.
Drug: Fexinidazole

Detailed Description:

Human African Trypanosomiasis (HAT) is a life-threatening and neglected disease.

Few treatment options are currently available for stage 2 (meningo-encephalitic stage) HAT, with NECT being the most commonly used one since 2010. Though NECT represents a significant improvement over current therapies, it is still far from ideal given the environment in which HAT patients live (remote, poor areas with little health infrastructure, if any, and difficult logistics). There is an urgent need for less toxic and more easily manageable compounds to treat this fatal disease.

Fexinidazole is a 2-5-nitroimidazole, formulated for oral administration, which has been shown to possess in vitro and in vivo activity against both T. b. rhodesiense and T. b. gambiense parasites.

Predicted CSF concentrations reached target levels after repeated dosing. Its efficacy and safety must now be tested in patients with stage 2 HAT.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 15 years old or more
  • Male or female
  • Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
  • Karnofsky index>50 (see Appendix 2 - Karnofsky Scale; p81)
  • Parasitologically confirmed late-stage African trypanosomiasis infection with T. b. gambiense in the blood and/or lymph and/or CSF, attested by mobile team report (with detail of exams performed and values of WBC measured in CSF) or done at the study centre. If parasitologically negative in CSF, WBC >20/µl detected in the CSF to document stage 2 infection.
  • Having a permanent address and able to comply with follow-up visit schedule
  • Signed Informed Consent Form

Exclusion Criteria:

  • Severely malnourished patients, defined as having a BMI < 16.
  • Patients unable to take oral medication.*
  • Pregnancy or lactation
  • Active clinically relevant medical conditions that, in the Investigator's opinion, may jeopardize subject safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, active documented or suspected infection, CNS trauma or seizure disorders, coma or altered consciousness.
  • Severely deteriorated general condition, such as cardiovascular shock, respiratory distress, or terminal illness.
  • Any condition which compromises ability to communicate with the Investigator as required for the completion of this study.
  • Any contraindication to imidazole products (known hypersensitivity to imidazoles) and NECT (known hypersensitivity to eflornithine).
  • Patients previously treated for HAT.
  • Patients previously enrolled in the study.
  • Follow-up expectable difficulties (migrants, refugees, traders, etc.).
  • History of alcohol abuse or any drug addiction.
  • Clinically significant abnormal laboratory value
  • Pregnancy
  • Unstable ECG abnormalities
  • QTcF≥ 450 msec in resting position (confirmed by 2 measurement).
  • Patients not tested for malaria and/or treated adequately for this infection
  • Patients not treated adequately for soil transmitted helminthic diseases
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685827

Contacts
Contact: Antoine Tarral, MD atarral@dndi.org
Contact: Francois Simon +41791967868 fsimon@dndi.org

Locations
Central African Republic
Batangafo Recruiting
Batangafo, Central African Republic
Principal Investigator: Francis Regongbenga, MD         
Congo
Masi Manimba Hospital Recruiting
Masi Manimba, Bandundu - DRC, Congo
Contact: Willy Kuziena, MD         
Principal Investigator: Willy Kuziena, MD         
Vanga Hospital Recruiting
Vanga, Bandundu - DRC, Congo
Principal Investigator: Jean-Pierre Fina, MD         
HGR Mushie hospital Recruiting
Mushie, Bandundu, Congo
Contact: Guylain Mandula, MD       gmandula@dndi.org   
Principal Investigator: Guylain mandula, MD         
CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital Recruiting
Mbuji Mayi, East Kasai, Congo
Contact: , MD         
Principal Investigator: Médard Ilunga, MD         
HS Katanda hospital Recruiting
Katanda, Kasaï Oriental, Congo
Contact: Lewis KANINDA BADIBABI         
Principal Investigator: Lewis KANINDA BADIBABI, MD         
HGR ISANGI hospital Recruiting
Isangi, Province orientale, Congo
Contact: KASONGO BONAMA         
Principal Investigator: KASONGO BONAMA, MD         
HGR (General Reference Hospital) Bandundu Recruiting
Bandundu, Congo
Principal Investigator: Pathou Nganzobo, MD         
Dingila Recruiting
Dingila, Congo
Principal Investigator: Josué Amici, MD         
Sponsors and Collaborators
Drugs for Neglected Diseases
Investigators
Principal Investigator: Victor KANDE, MD HAT National Control Program in DRC
  More Information

Additional Information:
No publications provided

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT01685827     History of Changes
Other Study ID Numbers: DNDiFEX004
Study First Received: September 12, 2012
Last Updated: June 19, 2014
Health Authority: Congo, Democratic Republic of the: Ministry of Health

Additional relevant MeSH terms:
Trypanosomiasis
Trypanosomiasis, African
Euglenozoa Infections
Parasitic Diseases
Protozoan Infections
Eflornithine
Nifurtimox
Anti-Infective Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on October 20, 2014