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

Primary Purpose

Visceral Leishmaniasis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Liposomal amphotericin B (Ambisome)
Liposomal amphotericin B (Ambisome)
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Visceral Leishmaniasis

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arba Minch LRTC
  • Gondar
  • Kassab Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Ambisome control:

Ambisome test

Arm Description

Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21

Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Parasitological clearance at day 30.

Full Information

First Posted
January 29, 2009
Last Updated
January 20, 2016
Sponsor
Drugs for Neglected Diseases
Collaborators
Addis Ababa University
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1. Study Identification

Unique Protocol Identification Number
NCT00832208
Brief Title
Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With VL
Official Title
Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Study Start Date
April 2009 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
Collaborators
Addis Ababa University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Visceral Leishmaniasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ambisome control:
Arm Type
Active Comparator
Arm Description
Ambisome, Total dose 21.0 mg given as 7 x 3mg on days 1,2,3,4,5, and 14 and 21
Arm Title
Ambisome test
Arm Type
Experimental
Arm Description
Single dose Ambisome in sequence(7.5 / 10.0/ 12.5 / 15.0mg)
Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B (Ambisome)
Other Intervention Name(s)
Ambisome
Intervention Description
21.0 mg/kg total dose. Given iv as 3mg/kg/day on days 1,2,3,4,5, and 14 and 21
Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B (Ambisome)
Other Intervention Name(s)
Ambisome
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Time Frame
at 6 months post treatment
Secondary Outcome Measure Information:
Title
Parasitological clearance at day 30.
Time Frame
Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sisay Yifru, MD
Organizational Affiliation
Gondar University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arba Minch LRTC
City
Arba Minch
Country
Ethiopia
Facility Name
Gondar
City
Gondar
Country
Ethiopia
Facility Name
Kassab Hospital
City
Kassab
State/Province
Gedarif
Country
Sudan

12. IPD Sharing Statement

Citations:
PubMed Identifier
24454970
Citation
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.
Results Reference
derived
PubMed Identifier
21375777
Citation
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.
Results Reference
derived

Learn more about this trial

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

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