Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01980199
Other study ID # FEXI VL 001
Secondary ID
Status Terminated
Phase Phase 2
First received November 4, 2013
Last updated October 29, 2015
Start date November 2013
Est. completion date September 2015

Study information

Verified date July 2014
Source Drugs for Neglected Diseases
Contact n/a
Is FDA regulated No
Health authority Sudan: National Medicines and Poisons Board
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Terminated
Enrollment 14
Est. completion date September 2015
Est. primary completion date November 2014
Accepts healthy volunteers No
Gender Both
Age group 15 Years to 60 Years
Eligibility Inclusion Criteria:

- Patients with clinical signs and symptoms of primary VL (fever for at least 2 weeks, splenomegaly) and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow) on microscopy.

- Patients aged between 15 and 60 years (inclusive) who are able to comply with the protocol.

- Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age together with the patients assent.

- HIV negative status

Exclusion Criteria:

- Patients who have previously been diagnosed with VL and received anti-leishmanial treatment (ie relapse)

- Patients with BMI <16 kg/m2

- Patients with contra-indication (known hypersensitivity) to other imidazoles (e.g. ketaconazole)

- Patients suffering from a concomitant severe underlying disease (cardiac, renal, hepatic) including hepatitis B, para kala-azar dermal leishmaniasis and tuberculosis

- Patient with clinically significant ECG findings or QTcF= 450 msec in 2 successive ECGs

- Major surgical intervention 4 weeks prior to enrollment.

- Patients who are pregnant or lactating.

- Female patients of child bearing age who do not agree to use an acceptable method of contraception

- Patients with haemoglobin < 5g/dl.

- Patients with platelets < 40,000/mm³.

- Patients with liver function (ALT and AST) tests of more than 2 times the upper limit of the normal range.

- Patients with serum creatinine above the normal range for age and gender.

- Patients with serum potassium (K+) above the normal range

- Patients with Bilirubin more than 1.5 times the upper limit of the normal range

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Fexinidazole
600 mg tablets given orally, after the main daily meal at the daily dose of 1800 mg (3 tablets) once a day for 4 days continued by 1200mg (2 tablets)once a day for 6 days

Locations

Country Name City State
Sudan Doka Hospital Doka Gedaref

Sponsors (1)

Lead Sponsor Collaborator
Drugs for Neglected Diseases

Country where clinical trial is conducted

Sudan, 

Outcome

Type Measure Description Time frame Safety issue
Other Safety endpoint Proportion of patients with SAE and/or AEs leading to treatment discontinuation From first dose of trial medication to day 56 for non serious AEs and to day 210 for SAEs Yes
Other Safety endpoint Proportion of patients experiencing at least one non-serious treatment emergent AE From first dose of trial medication to day 56 Yes
Other Pharmacokinetic assessment 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) From day 1 to day 12 No
Other Pharmacodynamic assessment Parasite load in blood and bone marrow (if remainder of bone marrow aspirate sample) to follow parasite clearance rate Screening, D1, D3, D5, D8, D11, D14, D28, D56, D210 No
Primary Initial cure Proportion of patients with an abscence of parasites in tissue aspirate and no rescue treatment administered up to and including day 28 Day 28 No
Secondary Final cure 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 Day 210 No
See also
  Status Clinical Trial Phase
Terminated NCT02839603 - Asymptomatic Leishmania Infection in HIV Patients
Completed NCT00370825 - Combination Chemotherapy for the Treatment of Indian Kala-Azar Phase 2
Recruiting NCT05426577 - Evaluation of Less Invasive Procedures for Visceral Leishmaniasis Treatment Efficacy Monitoring Test of Cure
Completed NCT01069198 - A Community Trial for Visceral Leishmaniasis (VL) N/A
Completed NCT00371995 - Short Course of Miltefosine and Liposomal Amphotericin B for Kala-azar Phase 2
Completed NCT01032187 - Amphotericin B to Treat Visceral Leishmaniasis in Brazilian Children Phase 4
Completed NCT00604955 - Expand Access/Assess Safety and Efficacy of Paromomycin IM Injection for the Treatment of Visceral Leishmaniasis Phase 4
Completed NCT00342823 - Immunogenetics of Visceral Leishmaniasis N/A
Completed NCT04003532 - LAMP Assay for the Diagnosis of Visceral Leishmaniasis
Completed NCT00255567 - Efficacy/Safety of Sodium Stibogluconate (SSG) Versus Paromomycin (PM) and SSG/PM Combination to Treat V Leishmaniasis Phase 3
Not yet recruiting NCT06118749 - Leishmania Antigen Rapid Diagnostic Test Proof-of-Concept and Validation Study
Recruiting NCT04342715 - A Study to Assess Immune Response Status in Patients Before and After Treatment for Visceral Leishmaniasis
Completed NCT02431143 - Pharmacokinetics/Safety of Miltefosine Allometric Dose for the Treatment of Visceral Leishmaniasis in Children in Eastern Africa Phase 2
Completed NCT01122771 - Phase III, Study of Three Short Course Combo (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome for the Treatment of VL in Bangladesh Phase 3
Completed NCT03636659 - Steady State Global Bioequivalence Study of Amphotericin B Liposome for Injection 50 mg/ Vial in Fed Condition Phase 1
Not yet recruiting NCT01566552 - Single Dose Liposomal Amphotericin B for Visceral Leishmaniasis Phase 4
Completed NCT00696969 - Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens for Visceral Leishmaniasis Phase 3
Completed NCT00318721 - Efficacy, Acceptability and Cost-effectiveness of Long Lasting Insecticide Nets (LLIN) in the Prevention of Kala Azar N/A
Completed NCT00216346 - Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis Phase 3
Completed NCT02011958 - Efficacy Trial of Ambisome Given Alone and Ambisome Given in Combination With Miltefosine for the Treatment of VL HIV Positive Ethiopian Patients. Phase 3