Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense

NCT03974178 | Completed Phase 2 Results DMC

• 1 other identifier: DNDi-FEX-07-HAT
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 2

Brief Summary

The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:

• Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
• Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
• Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
• Is fexinidazole treatment safe in patient with r-HAT, regardless of stage? Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 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.

Conditions

Trypanosomiasis, African; Sleeping Sickness; Trypanosoma Brucei Rhodesiense; Infection

Keywords

Trypanosoma Brucei (T. b.) rhodesiense; HAT; Neglected Tropical Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole

  The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the Data Safety Monitoring Board (DSMB), was calculated. The World Health Organization(WHO) verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.

  12 to 18 days after start of treatment

Secondary Outcomes (10)

• Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization

  12 to 18 days after start of treatment

• Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months

  12 months after start of treatment

• Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization

  12 to 18 days after start of treatment

• Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months

  12 months after start of treatment

• Percentage of Evaluable Patients With Any r-HAT Stage Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole

  12 to 18 days after start of treatment

Study Arms (2)

Patients with stage 1 r-HAT

EXPERIMENTAL

Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL. Patients were to receive fexinidazole orally for 10 days.

Drug: Fexinidazole

Patients with stage 2 r-HAT

EXPERIMENTAL

Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL. Patients were to receive fexinidazole orally for 10 days.

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)

Patients with stage 1 r-HAT; Patients with stage 2 r-HAT

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:

• 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 confirmation 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

You may not qualify if:

• 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
• Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
• 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

Sponsors & Collaborators

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

Study Sites (2)

Rumphi District Hospital

Rumphi, PO Box 225, Malawi

Location

Lwala Hospital

Lwala, Kadeberamaido, PO Box 650, Uganda

Location

Related Publications (1)

• Matovu E, Nyirenda W, Eriatu A, Alves D, Perdrieu C, Lemerani M, Wamboga C, Lejon V, Seixas J, Signorell A, Reymondier A, Baudin E, Scherrer B, Valverde Mordt O. Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2-3, non-randomised study. Lancet Glob Health. 2025 May;13(5):e910-e919. doi: 10.1016/S2214-109X(25)00016-6.

  PMID: 40288400 DERIVED

MeSH Terms

Conditions

Trypanosomiasis, African; Infections; Neglected Diseases

Interventions

fexinidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The main limitation is the benchmark study design. A direct comparison with melarsoprol was impossible due to its toxicity (5% of patients die due to treatment-related encephalopathy) and the rarity of r-HAT cases. The annual number of r-HAT cases in all endemic countries decreased from 110 patients in 2012 to 27 in 2017. Although the primary endpoint required a subjective assessment of the cause of death, this was performed by independent experts from the safety committee to ensure robustness.

Results Point of Contact

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

ovalverde@dndi.org

+41229069239/+41795431713

Study Officials

• Enock Matovu, Prof

  Makerere University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: June 4, 2019
• Study Start: September 29, 2019
• Primary Completion: November 30, 2021
• Study Completion: October 12, 2022
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1); MA (1)