Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With VL

Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis

This is a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. In this trial, the minimum effective dose will be determined in a sequential step, dose escalation design, which minimises the number of patients exposed to low, potentially inadequate doses and provides contemporaneous comparative data against the manufacturer's recommended dose schedule in this indication.

Study Overview

• Status: Terminated
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Drug: Liposomal amphotericin B (Ambisome); Drug: Liposomal amphotericin B (Ambisome)

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ethiopia
  • Arba Minch, Ethiopia
    • Arba Minch LRTC
  • Gondar, Ethiopia
    • Gondar
• Sudan
  • Gedarif
    • Kassab, Gedarif, Sudan
      • Kassab Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female adults and children aged 4 years or older with no upper age limit (in accordance with manufacturer's instructions)
• Acute, symptomatic, VL proven by parasitological examination of splenic aspirate (or bone marrow aspirate) with initial parasite index of at least 2+
• Haemoglobin >4g/dL
• Fever for more than 2 weeks
• Living within reachable distance of the trial site to enable attendance for follow-up visits
• Written informed consent to participate (for children, by parent or guardian)
• HIV negative status

Exclusion Criteria:

• Patients 'in extremis' with signs/symptoms indicative of severe VL
• Patients who have received any anti-leishmanial treatment within the last 6 months
• Patients who have received any investigational (unlicensed) drugs during 6 months before recruitment
• Known underlying chronic disease, such as severe cardiac, pulmonary, renal, or hepatic impairment.
• Renal function tests (serum creatinine) outside the normal range
• Liver function tests more than 3 times the normal range at study entry
• Platelet count less than 40,000/ mm3
• Known alcohol abuse
• Pregnancy or lactation
• Concomitant acute drug usage for malaria and bacterial infection, pneumonia within last 7 days
• Known hypersensitivity to AmBisome or amphotericin B
• Any other condition which may invalidate the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ambisome control: Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21	Drug: Liposomal amphotericin B (Ambisome); 21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21; Other Names: Ambisome; Drug: Liposomal amphotericin B (Ambisome); liposomal amphotericin b given intravenously as single dose at 7.5 mg/kg increasing to 10, 12.5 and 15.0mg/kg depending on results of interim analyses.; Other Names: Ambisome
Experimental: Ambisome test; Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg)	Drug: Liposomal amphotericin B (Ambisome); 21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21; Other Names: Ambisome; Drug: Liposomal amphotericin B (Ambisome); liposomal amphotericin b given intravenously as single dose at 7.5 mg/kg increasing to 10, 12.5 and 15.0mg/kg depending on results of interim analyses.; Other Names: Ambisome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration.	at 6 months post treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Parasitological clearance at day 30.	Day 30

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Collaborators: Addis Ababa University
• Investigators: Principal Investigator: Sisay Yifru, MD, Gondar University

Publications and helpful links

General Publications

• Khalil EA, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid AA, Dorlo TP, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AM, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.
• Edwards T, Omollo R, Khalil EA, Yifru S, Musa B, Musa A, Wasunna M, Smith PG, Royce C, Ellis S, Balasegaram M, Hailu A. Single-dose liposomal amphotericin B (AmBisome(R)) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Mar 6;12:66. doi: 10.1186/1745-6215-12-66.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: January 29, 2009
• First Submitted That Met QC Criteria: January 29, 2009
• First Posted (Estimate): January 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: AMBI 0106