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

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ClinicalTrials.gov Identifier: NCT03974178
Recruitment Status : Not yet recruiting
First Posted : June 4, 2019
Last Update Posted : June 4, 2019
Sponsor:
Collaborator:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Drugs for Neglected Diseases

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 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)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: Fexinidazole

All adults and children with a body weight ≥ 35 kg:

  • 1800 mg (3 tablets) from day 1 to 4
  • 1200 mg (2 tablets) from day 5 to 10

Children 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




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 hospitalization. Failure is defined as: death or presence of trypanosomes in any body fluid 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)



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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 12 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
  • Any contraindication to nitroimidazole class (known hypersensitivity to imidazoles) or to any of the excipients
  • Patients previously enrolled in the study or having already received fexinidazole
  • First trimester of pregnancy
  • Patients with severe hepatic impairment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03974178


Contacts
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Contact: Christelle Perdrieu +41229069236 cperdrieu@dndi.org
Contact: Olaf Valverde, Dr +41229069239 ovalverde@dndi.org

Sponsors and Collaborators
Drugs for Neglected Diseases
European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
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Principal Investigator: Enock Matovu, Prof Makerere University

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Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT03974178     History of Changes
Other Study ID Numbers: DNDi-FEX-07-HAT
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Trypanosomiasis
Trypanosomiasis, African
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases