NCT01122771

Phase III, Study of Three Short Course Combo (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome for the Treatment of VL in Bangladesh

A Phase III, Open Label, Randomised, Study of Three Short Course Combination Regimens (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome® Alone for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 602 (actual)
• Sponsor: Drugs for Neglected Diseases · Academic / Other
• Sex: All
• Age: 5 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This protocol will evaluate the efficacy and safety of various combinations of the three drugs; AmBisome, Paromomycin and Miltefosine at reduced total dosage against the standard treatment with a total dose of 15mg/kg of AmBisome.

Detailed description

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. The causative parasite in Bangladesh is almost exclusively L. donovani. • The current treatment options in Bangladesh are not satisfactory as they are either toxic and long, or are of limited use in women of childbearing age due to possible teratogenicity, long treatment duration which leads to non-compliance and possible emergence of resistance or expensive. In collaboration with Indian Medical Research Council and investigators in India, DNDi initiated a combination trial for treatment of VL in Bihar, India in 2008 including 624 patients from age 5 - 60. The same combinations will be used in the present study. An interim safety review was conducted on the first 120 patients included in the Indian VL Combination study and revealed no safety issues with combination treatment. The enrolment is complete and the final results for 624 patients are expected in Q1 2010. This is a randomized, controlled, open-label, parallel group study to compare the safety and efficacy of different combination regimens with AmBisome for the treatment of VL in Bangladesh. This trial is designed in two steps: Step 1: First 120 patients will be recruited in a hospital setting in a study including parasitology and laboratory assessments at Community Based Medical College, Bangladesh (CBMC,B), primarily for the purpose of reconfirming the safety of combination treatments in Bangladesh. Pending the review and approval of an independent DSMB of the Day 45 data, step 2 will commence. Step 2: Approximately 554 Patients will then be recruited and treated in Upazilla Health Centre's (UZHC), situated in endemic regions of Bangladesh. We will use rapid diagnostic test (RDT) and the limited laboratory assessments that are available in the centres. Female patients will be stratified according to marital status, such that unmarried women of child-bearing age will be stratified to receive treatments that do not contain Miltefosine, and married women will be stratified to receive one of the four treatment regimens and must consent to use an approved method of contraception and undergo pregnancy test at the start of the study. Child-bearing age is defined as achieving menarche. There will be one planned safety review assessing safety and initial cure at Day 45 following completion of Step 1.

Conditions

• Visceral Leishmaniasis

Interventions

Type	Name	Description
DRUG	Liposomal amphotericin B	Ambisome i.v. 5mg on days 1, 3 and 5
DRUG	liposomal amphotericin B + miltefosine	Ambisome 5mg single dose iv Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10)
DRUG	liposomal amphotericin B + paromomycin	Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10) + Paromomycin base 11mg/kg/day IM for 10 days (days 1-10).
DRUG	Miltefosine + Paromomycin	Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10) + Paromomycin base 11mg/kg/day IM for 10 days (days 1-10).

Timeline

• Start date: 2010-05-01
• Primary completion: 2014-03-01
• Completion: 2014-03-01
• First posted: 2010-05-13
• Last updated: 2016-01-21

Locations

4 sites across 1 country: Bangladesh