Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
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|ClinicalTrials.gov Identifier: NCT01685827|
Recruitment Status : Completed
First Posted : September 14, 2012
Last Update Posted : February 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Human African Trypanosomiasis (HAT) Sleeping Sickness||Drug: Fexinidazole Drug: Nifurtimox Drug: Eflornithine||Phase 2 Phase 3|
Human African Trypanosomiasis (HAT) is a life-threatening and neglected disease.
Few treatment options are currently available for stage 2 (meningo-encephalitic stage) HAT, with NECT being the most commonly used one since 2010. Though NECT represents a significant improvement over current therapies, it is still far from ideal given the environment in which HAT patients live (remote, poor areas with little health infrastructure, if any, and difficult logistics). There is an urgent need for less toxic and more easily manageable compounds to treat this fatal disease.
Fexinidazole is a 2-5-nitroimidazole, formulated for oral administration, which has been shown to possess in vitro and in vivo activity against both T. b. rhodesiense and T. b. gambiense parasites.
Predicted CSF concentrations reached target levels after repeated dosing. Its efficacy and safety must now be tested in patients with stage 2 HAT.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||394 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Efficacy and Safety of Fexinidazole Compared to Nifurtimox-Eflornithine Combination Therapy (NECT) in Patients With Late-stage Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: Pivotal, Non-inferiority, Multicentre, Randomised, Open-label Study|
|Study Start Date :||October 2012|
|Actual Primary Completion Date :||November 11, 2016|
|Actual Study Completion Date :||April 26, 2017|
Active Comparator: NECT (Nifurtimox Eflornithine Combination Therapy)
Other Name: Lampit
Other Name: Ornidyl
Fexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of:
- success or failure at 18 months FU visit [ Time Frame: 18 months after treatment ]
The primary endpoint is the outcome (success or failure) at the test of cure (ToC) visit 18 months after the end of treatment (EOT) adapted from WHO criteria.
Success at 18 months is:
- patient alive,
- AND with no evidence of trypanosomes in any body fluid,
- AND 20 or less WBC/µl CSF
Or Probable cure:
- Patient with no parasitological evidence of relapse in blood and lymph
- AND who refuses lumbar puncture OR whose CSF sample is haemorrhagic without trypanosomes
- AND whose clinical condition is satisfactory (without clinical symptom or signs) OR whose clinical status is unlikely to be due to HAT
- Safety endpoint [ Time Frame: 18 days - observation period ]
Occurrence of any grade (all grades combined) adverse events during the observation period (D1-18) including:
- any worsening of clinical symptoms listed in the inclusion checklist of symptoms and signs,
- laboratory abnormalities of grade ≥ 2
- Occurrence of grade ≥ 3 adverse events during the observation period
- Occurrence of drug-related adverse events (grade ≥ 3 and any grade) during the observation period
- Safety endpoint [ Time Frame: 24 months ]Occurrence of any serious adverse events from first drug intake to the end of follow-up period (18 months), and from M18 to M24.
- Pharmacokinetics endpoint [ Time Frame: from D8 to D12 after first dosing ]Whole blood and CSF concentrations of fexinidazole, M1, M2 and PK parameters derived from a model of population PK data.
- QT evaluation [ Time Frame: D0 - D4 - D10 ]recording of triplicates ECG
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): NCT01685827
|Central African Republic|
|Batangafo, Central African Republic|
|Congo, The Democratic Republic of the|
|Bagata, Bandundu, Congo, The Democratic Republic of the|
|Masi Manimba Hospital|
|Masi Manimba, Bandundu - DRC, Congo|
|Vanga, Bandundu - DRC, Congo|
|HGR Mushie hospital|
|Mushie, Bandundu, Congo|
|CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital|
|Mbuji Mayi, East Kasai, Congo|
|HS Katanda hospital|
|Katanda, Kasaï Oriental, Congo|
|HGR ISANGI hospital|
|Isangi, Province Orientale, Congo|
|HGR (General Reference Hospital) Bandundu|
|Principal Investigator:||Victor KANDE, MD||HAT National Control Program in DRC|