Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
Human African Trypanosomiasis (HAT)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|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|
- success or failure at 18 months FU visit [ Time Frame: 18 months after treatment ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]recording of triplicates ECG
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Active Comparator: NECT (Nifurtimox Eflornithine Combination Therapy)
Other Name: LampitDrug: Eflornithine
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:
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01685827
|Central African Republic|
|Batangafo, Central African Republic|
|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|