Trial to Determine Efficacy of Fexinidazole in Visceral Leihmaniasis Patients in Sudan
This study is designed to determine the efficacy of Fexinidazole as an oral treatment in Visceral Leishmanisasis sudanese adults patients.
The results of this proof of concept study will allow to make a decision on whether to proceed with clinical development of Fexinidazole for visceral leishmaniasis.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Proof of Concept Trial to Determine Efficacy of Fexinidazole in Visceral Leishmaniasis Patients in Sudan|
- Initial cure [ Time Frame: Day 28 ] [ Designated as safety issue: No ]Proportion of patients with an abscence of parasites in tissue aspirate and no rescue treatment administered up to and including day 28
- Final cure [ Time Frame: Day 210 ] [ Designated as safety issue: No ]Proportion of patients initially cured at day 28 (or day 56 for slow responders) with no further signs or symptoms of visceral leishmaniasis and no requirement for rescue medication during follow-up phase up to and including the day 210
- Safety endpoint [ Time Frame: From first dose of trial medication to day 56 for non serious AEs and to day 210 for SAEs ] [ Designated as safety issue: Yes ]Proportion of patients with SAE and/or AEs leading to treatment discontinuation
- Safety endpoint [ Time Frame: From first dose of trial medication to day 56 ] [ Designated as safety issue: Yes ]Proportion of patients experiencing at least one non-serious treatment emergent AE
- Pharmacokinetic assessment [ Time Frame: From day 1 to day 12 ] [ Designated as safety issue: No ]Whole blood concentration of Fexinidazole and metabolites (sulfone and sulfoxide) in an intensive cohort of 10 patients (18 sampling time points) and in a regular cohort for all other patients (6 sampling time points)
- Pharmacodynamic assessment [ Time Frame: Screening, D1, D3, D5, D8, D11, D14, D28, D56, D210 ] [ Designated as safety issue: No ]Parasite load in blood and bone marrow (if remainder of bone marrow aspirate sample) to follow parasite clearance rate
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||September 2015|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
3 tablets once a day for 4 days continued by 2 tablets once a day for 6 days
600 mg tablets given orally, after the main daily meal
Visceral Leishmaniasis (VL) is a neglected disease and it is fatal if left untreated.
Until recently the first line treatment in East Africa was 30 days of Sodium Stibogluconate which can be cardiotoxic. Since 2010 WHO recommended Sodium Stibogluconate and Paromomycin for 17 days which is a shorter treatment but there remains the toxicity associated with these drugs. The second line treatment is Ambisome given as 6-10 intravenous infusions, whilst this has a better safety profile than other VL regimens it is expensive.
So there is an urgent need for short course oral treatment for VL particularly in the East African region.
Fexinidazole is a 2 substituted 5-nitroimidazole formulated for oral administration. Fexinidazole through its metabolites has demonstrated potent activity againts L. donovani intracellular amastigotes in vitro and in vivo in a visceral leishmaniasis mouse model.
The dose selected for this study (1800 mg/1200 mg for 4/6 days) has been based on the dose selected for a phase II trial on Human African Trypasonomiasis. It is albeit well tolerated and is one dose level below the maximum tolerated dose level established in phase I.
The trial is designed and will be analysed according to a sequential method known as the triangular test, using day 28 data. This sequential design allows for repeated interim analysis (every 10 patients). The null hypothesis is that the proportion cured is less than or equal to 75%. The primary endpoint is initial cure at day 28. The primary population for interim analyses and interim decision making will be the per protocol population.In the final analysis of cumulative patient data, Intention to Treat and Per Protocol Population analyses will be conducted.
The conventional 6 months (day 210) follow up outcome is still an important secondary endpointfor the final decision on whether to proceed with clinical development of Fexinidazole for VL.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01980199
|Doka, Gedaref, Sudan|
|Principal Investigator:||Ahmed M Musa, MD PhD||Director, Institute of Endemic Diseases, University of Khartoum Associate Professor, Head, Department of Clinical Pathology & Immunology|
|Principal Investigator:||E. AG Khalil, Prof. MD||Institute of Endemic Diseases (IED), University of Khartoum|