Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

NCT ID: NCT03025789

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-10
• Study Completion Date: 2021-02-01

Brief Summary

This study evaluates the effectiveness of fexinidazole administered to patients with human African trypanosomiasis due to T. b. gambiense (g-HAT) at all stages of the disease. The aim of the present study is to provide additional information on the effectiveness and safety of fexinidazole and to assess its use under conditions as close as possible to those in real life, both in patients treated on an out-patient basis and in the hospital setting, depending on clinical status.

Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 18 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms. Treatment compliance, feasibility, and packaging acceptability will be thoroughly assessed in the participants receiving treatment at home. Those participants will complete questionnaires to check that instructions for fexinidazole administration are clear enough and followed correctly.

Detailed Description

See attached protocol.

Conditions

Trypanosomiasis, African; Sleeping Sickness; Trypanosomiasis; Gambian

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inpatients

Participants received fexinidazole orally for 10 days as inpatients (at the hospital)

Group Type: EXPERIMENTAL

Fexinidazole

Intervention Type: DRUG

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Outpatients

Participants received fexinidazole orally for 10 days as outpatients (at home)

Group Type: EXPERIMENTAL

Fexinidazole

Intervention Type: DRUG

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Interventions

Fexinidazole

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patient, including breastfeeding or pregnant women in the second or third trimester.
• ≥ 6 years of age.
• ≥ 20 kg body weight.
• Signed Informed Consent Form and Assent Form for patients less than 18 years of age
• Trypanosomes detected in any body fluid.
• Physically able to ingest at least one solid meal per day.
• Able to take oral medication.
• Karnofsky Performance Status > 40%.
• Able to comply with the schedule of follow-up visits and with the study constraints.
• Easily reachable during the out-patient follow-up period.
• Willing to undergo lumbar punctures.

• Recovery period after antimalarial treatment and/or treatment of helminthiasis (at least 3 days).
• Uncontrolled diabetes or hypertension or any patients requiring clinical stabilization; wait until appropriate treatment to control the disease has been initiated.
• First trimester of pregnancy.
• Traumatic lumbar puncture at Screening i.e. red blood cells visible in cerebrospinal fluid (CSF); wait for 48 hours before repeating lumbar puncture.

Eligibility Criteria for Out-patient Treatment

• Accepting to be treated on an out-patient basis;
• Karnofsky Performance Status > 50%;
• Good understanding of the method of administration of fexinidazole by the patient and/or caregiver* (checked using a questionnaire at the time of dispensing fexinidazole);
• Residing close to the investigational center, i.e. approximately one hour by road and/or boat, during the treatment period**;
• Easily reachable during the treatment period;
• No medical or psychiatric contraindications for treatment as out-patient;
• No pregnancy or breastfeeding;
• No neurological symptoms.

Exclusion Criteria

• Active clinically relevant medical conditions other than HAT that, in the Investigator's opinion, could jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular diseases, human immunodeficiency virus (HIV) infection, central nervous system (CNS) trauma or seizure disorders, coma or altered consciousness not related to HAT.
• Severe renal or hepatic impairment defined as:

elevated creatinine at > 3 times the upper limit of normal (ULN); elevated alanine aminotranferase (ALT), aspartate aminotransferase (AST), or bilirubin at > 3 ULN

• Severely deteriorated general condition, such as cardiovascular shock, respiratory distress or terminal illness.
• Any condition (except symptoms of HAT) that compromises ability to communicate with the Investigator as required for completion of the study.
• Any contraindication to imidazole products (known hypersensitivity to imidazoles).
• Treatment for HAT within 2 years prior to inclusion.
• Prior enrolment in the study or prior intake of fexinidazole.
• Foreseeable difficulty in complying with the schedule of follow-up visits (migrants, refugees, itinerant traders, etc.).

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victor Kande Betu Kumeso, MD

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health, Kinshasa, The Democratic Republic of the Congo

Mamadou Camara, PhD

Role: PRINCIPAL_INVESTIGATOR

National HAT Control Programme, Conakry, Guinea

Médard Ilunga Wa Kyhi, MD

Role: PRINCIPAL_INVESTIGATOR

National HAT Control Programme, Kinshasa, The Democratic Republic of the Congo

Digas Ngolo Tete, MPH

Role: PRINCIPAL_INVESTIGATOR

National HAT Control Programme, Kinshasa, The Democratic Republic of the Congo

Locations

Dipumba Hospital

Mbuji-Mayi, Kasaï Oriental Province, Democratic Republic of the Congo

Bagata Hospital

Bagata, Kwilu, Democratic Republic of the Congo

Bandundu Hospital

Bandundu Province, Kwilu, Democratic Republic of the Congo

Masi Manimba Hospital

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Nkara Secondary Hospital

Nkara, Kwilu, Democratic Republic of the Congo

Mushie Hospital

Mushie, Maï Ndombe Province, Democratic Republic of the Congo

Roi Baudouin Hospital

Kinshasa, , Democratic Republic of the Congo

Dubreka Hospital

Dubréka, , Guinea

Countries

Democratic Republic of the Congo; Guinea

References

WHO. Human African trypanosomiasis: update of the methodological framework for clinical trials: report of the first meeting of the Development of New Tools subgroup, Geneva, 24 September 2014. World Health Organization 2015. WHO/HTM/NTD/IDM/2015.5

Reference Type: BACKGROUND

Kumeso VKB, Perdrieu C, Menetrey C, Kyhi MIW, Tete DN, Camara M, Tampwo J, Kavunga P, Camara ML, Kourouma A, Mindele WK, Masa FA, Mahenzi H, Makaya J, Malu TM, Mandula G, Nzambi DMM, Ntoya SL, Reymondier A, Kalonji WM, Scherrer B, Mordt OV. Effectiveness and safety of fexinidazole for gambiense human African trypanosomiasis and exploration of adherence in outpatients: a phase 3b, prospective, open-label, non-randomised, cohort study. Lancet Glob Health. 2025 May;13(5):e900-e909. doi: 10.1016/S2214-109X(24)00526-6.

Reference Type: DERIVED

PMID: 40288399 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DNDi-FEX-09-HAT

Identifier Type: -

Identifier Source: org_study_id