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

Trypanosoma Brucei Rhodesiense; Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03974178
• Other study ID #: DNDi-FEX-07-HAT
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 29, 2019
• Est. completion date: October 12, 2022

Study information

• Verified date: October 2022
• Source: Drugs for Neglected Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 12, 2022
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Trypanosoma Brucei Rhodesiense; Infection
• Trypanosomiasis
• Trypanosomiasis, African

Intervention

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

Locations

Country	Name	City	State
Malawi	Rumphi District Hospital	Rumphi
Uganda	Lwala Hospital	Lwala	Kadeberamaido

Sponsors (2)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases	European and Developing Countries Clinical Trials Partnership (EDCTP)

Countries where clinical trial is conducted

Malawi,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients	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)	12 to 18 days after start of treatment
Secondary	Success rate at the End of Treatment in all stages patients	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	11 days after start of treatment
Secondary	Success and failure outcomes at the test of cure	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)	12 months after start of treatment
Secondary	Occurrence of adverse events and serious adverse events	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.	12 months after start of treatment
Secondary	Unsatisfactory clinical and parasitological response	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)	11 days after start of treatment