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

Primary Purpose

Trypanosoma Brucei Rhodesiense; Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fexinidazole
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Trypanosoma Brucei Rhodesiense; Infection focused on measuring Human African trypanosomiasis, neglected tropical disease, t.b. rhodesiense

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Rumphi District Hospital
  • Lwala Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fexinidazole

Arm Description

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

Outcomes

Primary Outcome Measures

Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients
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

Success rate at the End of Treatment in all stages patients
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
Success and failure outcomes at the test of cure
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)
Occurrence of adverse events and serious adverse events
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.
Unsatisfactory clinical and parasitological response
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)

Full Information

First Posted
May 23, 2019
Last Updated
October 21, 2022
Sponsor
Drugs for Neglected Diseases
Collaborators
European and Developing Countries Clinical Trials Partnership (EDCTP)
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1. Study Identification

Unique Protocol Identification Number
NCT03974178
Brief Title
Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
September 29, 2019 (Actual)
Primary Completion Date
November 30, 2021 (Actual)
Study Completion Date
October 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
Collaborators
European and Developing Countries Clinical Trials Partnership (EDCTP)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trypanosoma Brucei Rhodesiense; Infection
Keywords
Human African trypanosomiasis, neglected tropical disease, t.b. rhodesiense

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fexinidazole
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Fexinidazole
Intervention Description
Adults and Children patients will receive fexinidazole tablets every day for 10 days
Primary Outcome Measure Information:
Title
Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients
Description
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)
Time Frame
12 to 18 days after start of treatment
Secondary Outcome Measure Information:
Title
Success rate at the End of Treatment in all stages patients
Description
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
Time Frame
11 days after start of treatment
Title
Success and failure outcomes at the test of cure
Description
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)
Time Frame
12 months after start of treatment
Title
Occurrence of adverse events and serious adverse events
Description
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.
Time Frame
12 months after start of treatment
Title
Unsatisfactory clinical and parasitological response
Description
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)
Time Frame
11 days after start of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enock Matovu, Prof
Organizational Affiliation
Makerere University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rumphi District Hospital
City
Rumphi
ZIP/Postal Code
PO Box 225
Country
Malawi
Facility Name
Lwala Hospital
City
Lwala
State/Province
Kadeberamaido
ZIP/Postal Code
PO box 650
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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