Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense

Sponsor
Drugs for Neglected Diseases (Other)
Overall Status
Recruiting
CT.gov ID
NCT03974178
Collaborator
European and Developing Countries Clinical Trials Partnership (EDCTP) (Other)
50
Enrollment
2
Locations
1
Arm
41
Anticipated Duration (Months)
25
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims at evaluating the efficacy and safety of a new oral treatment drug against Human African trypanosomiasis (HAT) due to T.b rhodesiense. 34 patients will be recruited in 2 sites located in Malawi and Uganda. All patients will receive the study drug fexinidazole.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2/Phase 3

Detailed Description

Nowadays, the only treatment available for the stage 2 of HAT due to t.b rhodesiense is melarsoprol, a very toxic drug.

The primary objective of this trial is to evaluate fexinidazole as an alternative treatment over melarsoprol in patients with stage 2 of HAT disease due to t.b rhodesiense in a Phase II/III cohort trial with 34 stage 2 patients. All stages of the disease will be recruited but the recruitment will stop once 34 evaluable stage-2 patients have reached the end of treatment.

The trial will be a multicentre, non-randomized, clinical trial in patients with r-HAT.

Subjects will be recruited among the patients reporting to Lwala Hospital (Uganda) and Rumphi District Hospital (Malawi). If feasible, r-HAT patients from other hospitals and centres in Kaberamaido/Dokolo Districts (Uganda) and Rumphi/Mzimba North District (Malawi) and well as Zambia bordering areas, will be referred to Lwala and Rumphi Hospitals, respectively, for treatment.

Fexinidazole is an oral treatment which has to be taken every day for 10 days. In case of lack of efficacy (e.g. disease relapse) the patients will be switched to the standart treatment that is part of the National Control Program in each country (melarsoprol for stage-2 patients and suramin for stage-1 patients)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial
Actual Study Start Date :
Sep 29, 2019
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Fexinidazole

Patients with a body weight ≥ 35 kg: 1800 mg (3 tablets) from day 1 to 4 1200 mg (2 tablets) from day 5 to 10 Patients with a body weight ≥ 20 and < 35 kg: 1200 mg (2 tablets) from day 1 to 4 600 mg (1 tablet) from day 5 to 10

Drug: Fexinidazole
Adults and Children patients will receive fexinidazole tablets every day for 10 days

Outcome Measures

Primary Outcome Measures

  1. Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients [12 to 18 days after start of treatment]

    Death possibly related to r-HAT or treatment according to DSMB; since at the study sites anatomopathological techniques are not available, the completion of the WHO verbal autopsy questionnaire will be requested in case of death)

Secondary Outcome Measures

  1. Success rate at the End of Treatment in all stages patients [11 days after start of treatment]

    success is defined as: patient alive and no trypanosomes at end of treatment. Failure is defined as: presence of trypanosomes in any body fluid at end of treatment or death at End of hospitalization. Deaths to be considered are defined as possibly related to r-HAT or treatment according to DSMB. Unrelated deaths are neither success nor failure

  2. Success and failure outcomes at the test of cure [12 months after start of treatment]

    A modification of the WHO recommendations is used to determine success and failure for stage-1 and stage-2 r-HAT patients (Appendix I - Evaluation criteria of efficacy endpoints)

  3. Occurrence of adverse events and serious adverse events [12 months after start of treatment]

    3. Occurrence of adverse events, including abnormal laboratory or ECG findings, during the observation period (until the end of hospitalisation scheduled up to 7 days after EOT) and those considered as possibly related to r-HAT or treatment, among those detected until the end of the follow-up period (12-month visit). All serious adverse events (SAE) whether they are considered as possibly related to r-HAT treatment or not.

  4. Unsatisfactory clinical and parasitological response [11 days after start of treatment]

    defined as the compound analysis of the clinical evolution (symptoms of HAT) associated with presence of parasites in at least one body fluid (via blood test and/or lumbar puncture)

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Signed Informed Consent Form (plus assent for children)

  • ≥ 6 years old

  • ≥ 20 kg body weight

  • Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)

  • Karnofsky index ≥ 40

  • Parasitological confirmed of T.b. rhodesiense infection

  • Having a permanent address or being traceable by others and willing and able to comply with follow-up visit schedule

  • Agreement to be hospitalised for a minimum of 13 days and to receive the study treatment

Exclusion Criteria:
  • Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.

  • Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness

  • Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole) or to any of the excipients

  • Patients previously enrolled in the study or having already received fexinidazole

  • Patients with severe hepatic impairment (ex: clinical signs of cirrhosis or jaundice)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Rumphi District HospitalRumphiMalawiPO Box 225
2Lwala HospitalLwalaKadeberamaidoUgandaPO box 650

Sponsors and Collaborators

  • Drugs for Neglected Diseases
  • European and Developing Countries Clinical Trials Partnership (EDCTP)

Investigators

  • Principal Investigator: Enock Matovu, Prof, Makerere University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT03974178
Other Study ID Numbers:
  • DNDi-FEX-07-HAT
First Posted:
Jun 4, 2019
Last Update Posted:
Aug 30, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Drugs for Neglected Diseases
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 30, 2021