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出境医 / 临床实验 / Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense
Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense
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:
Patients with a body weight ≥ 20 and < 35 kg:
|
Drug: Fexinidazole
Adults and Children patients will receive fexinidazole tablets every day for 10 days
|
Outcome Measures
Primary Outcome Measures :
- 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 :
- 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
- 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)
- 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.
- 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: Christelle Perdrieu | +41229069236 | cperdrieu@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 |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 23, 2019 | ||||||||
| First Posted Date ICMJE | June 4, 2019 | ||||||||
| Last Update Posted Date | October 19, 2020 | ||||||||
| Actual Study Start Date ICMJE | September 29, 2019 | ||||||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
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)
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense | ||||||||
| Official Title ICMJE | Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial | ||||||||
| 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) |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 2 Phase 3 |
||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
| Condition ICMJE | Trypanosoma Brucei Rhodesiense; Infection | ||||||||
| Intervention ICMJE | Drug: Fexinidazole
Adults and Children patients will receive fexinidazole tablets every day for 10 days
|
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| Study Arms ICMJE | Experimental: Fexinidazole
Patients with a body weight ≥ 35 kg:
Patients with a body weight ≥ 20 and < 35 kg:
Intervention: Drug: Fexinidazole
|
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| Publications * | Not Provided | ||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
50 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | March 2023 | ||||||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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| Sex/Gender ICMJE |
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| Ages ICMJE | 6 Years and older (Child, Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Malawi, Uganda | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03974178 | ||||||||
| Other Study ID Numbers ICMJE | DNDi-FEX-07-HAT | ||||||||
| Has Data Monitoring Committee | Yes | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Drugs for Neglected Diseases | ||||||||
| Study Sponsor ICMJE | Drugs for Neglected Diseases | ||||||||
| Collaborators ICMJE | European and Developing Countries Clinical Trials Partnership (EDCTP) | ||||||||
| Investigators ICMJE |
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| PRS Account | Drugs for Neglected Diseases | ||||||||
| Verification Date | October 2020 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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