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

NCT03025789 | Completed Phase 3 Results DMC

• 1 other identifier: DNDi-FEX-09-HAT
• Study Type: interventional
• Target: 174
• Locations: 2 countries
• Sites: 8

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.

Conditions

Trypanosomiasis, African; Sleeping Sickness; Trypanosomiasis; Gambian

Keywords

T.b gambiense; HAT; outpatients

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Whose Treatment Outcome at Month 18 is a Success

  Treatment outcome at Month 18 is categorized as success or failure. Success is defined as a cure, according to the criteria adapted from the World Health Organization (WHO) update of the methodological framework for clinical trials in Sept 2014 (WHO/HTM/NTD/IDM/2015.5). Failure is defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 18 visit, an unfavorable outcome earlier than Month 18, or signs and symptoms evoking a relapse at Month 18. Success rate at Month 18 is defined as the percentage of participants (regardless of g-HAT stage) whose treatment outcome is a success at Month 18. An estimate of the success rate at Month 18 and the 95% exact Clopper-Pearson confidence interval (CI) of the estimate are provided.

  Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

Secondary Outcomes (18)

• Percentage of Participants Whose Treatment Outcome at Month 12 is a Success

  Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

• Number of Participants With Any Grade ≥ 3 Treatment-emergent Adverse Events (AEs) Including Laboratory and Hematological Abnormalities (if Considered Clinically Significant)

  Between the first intake of fexinidazole (Day 1) and the end of the observation period, or the end of the follow-up period (18 months) for non-serious AEs assessed as related to fexinidazole

• Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE)

  Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)

• Number of Participants With Any Temporary or Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety

  Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

• Number of Participants With Any Hospitalization for Reasons Related to Safety (Outpatients Only)

  Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)

Study Arms (2)

Inpatients

EXPERIMENTAL

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

Drug: Fexinidazole

Outpatients

EXPERIMENTAL

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

Drug: Fexinidazole

Interventions

Fexinidazole 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)

Inpatients; Outpatients

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.).
• 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%;

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Sanofi: collaborator

Study Sites (8)

Dipumba Hospital

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

Location

Bagata Hospital

Bagata, Kwilu, Democratic Republic of the Congo

Location

Bandundu Hospital

Bandundu Province, Kwilu, Democratic Republic of the Congo

Location

Masi Manimba Hospital

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

Nkara Secondary Hospital

Nkara, Kwilu, Democratic Republic of the Congo

Location

Mushie Hospital

Mushie, Maï Ndombe Province, Democratic Republic of the Congo

Location

Roi Baudouin Hospital

Kinshasa, Democratic Republic of the Congo

Location

Dubreka Hospital

Dubréka, Guinea

Location

Related Publications (2)

• 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

  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.

  PMID: 40288399 DERIVED

MeSH Terms

Conditions

Trypanosomiasis, African; Trypanosomiasis

Interventions

fexinidazole

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Limitations and Caveats

There is an overlap between the safety profile of fexinidazole and the g-HAT symptoms, making the interpretation of the safety data (in particular the relationship with fexinidazole) difficult as this was a cohort study and not a comparative study. Some study sites were involved in another clinical trial. A recruitment bias towards patients not filling the other trial's criteria (pregnant and breastfeeding women, children, and patients with Karnofsky score between 40 and 50) may have occurred.

Results Point of Contact

• Title: Dr. Olaf Valverde Mordt
• Organization: Drugs for Neglected Diseases initiative (DNDi)

ovalverde@dndi.org

+41795431713

Study Officials

• Victor Kande Betu Kumeso, MD

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

  PRINCIPAL INVESTIGATOR

• Mamadou Camara, PhD

  National HAT Control Programme, Conakry, Guinea

  PRINCIPAL INVESTIGATOR

• Médard Ilunga Wa Kyhi, MD

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

  PRINCIPAL INVESTIGATOR

• Digas Ngolo Tete, MPH

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: January 20, 2017
• Study Start: November 10, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: January 8, 2025
• Results First Posted: June 7, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); GU (1)