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

• ClinicalTrials.gov Identifier: NCT03974178
• Recruitment Status: Recruiting
• First Posted: June 4, 2019
• Last Update Posted: August 30, 2021
• Sponsor: Drugs for Neglected Diseases
• Collaborator: European and Developing Countries Clinical Trials Partnership (EDCTP)
• Information provided by (Responsible Party): Drugs for Neglected Diseases

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 disease	Intervention/treatment	Phase
Trypanosoma Brucei Rhodesiense; Infection	Drug: Fexinidazole	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 (Clinical Trial)
• Estimated 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: September 29, 2019
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: March 2023

Arms and Interventions

Arm	Intervention/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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts

Contact: Deolinda Alves; +41225551971; dalves@dndi.org

Contact: Olaf Valverde, Dr; +41229069239; ovalverde@dndi.org

Locations

Malawi

Rumphi District Hospital; Recruiting

Rumphi, Malawi, PO Box 225

Contact: Westain T Nyirenda, MD +265885110094 wnyirenda@extern.dndi.org

Contact: Fredrick Jumah fjumah@extern.dndi.org

Principal Investigator: Westain T Nyirenda, MD

Uganda

Lwala Hospital; Not yet recruiting

Lwala, Kadeberamaido, Uganda, PO box 650

Contact: Anthony Eriatu, MD +256 782 869 227 aeriatu@extern.dndi.org

Contact: Ruth Enyimu +256774933925

Principal Investigator: Anthony Eriatu, MD

Sponsors and Collaborators

Drugs for Neglected Diseases

European and Developing Countries Clinical Trials Partnership (EDCTP)

Investigators

• Principal Investigator: Enock Matovu, Prof; Makerere University

More Information

• Responsible Party: Drugs for Neglected Diseases
• ClinicalTrials.gov Identifier: NCT03974178
• Other Study ID Numbers: DNDi-FEX-07-HAT
• First Posted: June 4, 2019
• Last Update Posted: August 30, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• 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:

Human African trypanosomiasis; neglected tropical disease; t.b. rhodesiense

Additional relevant MeSH terms:

Trypanosomiasis; Trypanosomiasis, African; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases