Clinical Trial to Assess the Safety and Efficacy of Sodium Stibogluconate (SSG) and AmBisome® Combination, Miltefosine and AmBisome® and Miltefosine Alone for the Treatment Visceral Leishmaniasis in Eastern Africa

A Phase II Randomized, Parallel Arm, Open-labeled Clinical Trial to Assess the Safety and Efficacy of the Combination of Sodium Stibogluconate Plus Single Dose AmBisome®, Miltefosine Plus Single Dose AmBisome® and Miltefosine Alone for the Treatment of Primary Visceral Leishmaniasis in Eastern Africa

This study is to assess if shorter combinations of SSG plus single dose AmBisome®, Miltefosine plus single dose AmBisome® and Miltefosine alone are effective in treating visceral leishmaniasis in Eastern Africa.

Study Overview

• Status: Completed
• Conditions: Primary Visceral Leishmaniasis
• Intervention / Treatment: Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate; Drug: Liposomal amphotericin B + miltefosine; Drug: Miltefosine

Detailed Description

The current study intends to look at potential feasible short course combination therapies as well as evaluate (and possibly register) miltefosine in its conventional dose against VL in Sudan and Kenya.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2

Contacts and Locations

Study Locations

• Kenya
  • Kimalel, Kenya
    • Kimalel Health Centre
• Sudan
  • Gedaref
    • Kassab, Gedaref, Sudan
      • Kassab Hospital
  • Gedarif
    • Doka, Gedarif, Sudan
      • El Hassan Centre for Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with clinical signs and symptoms of VL and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow or spleen where relevant) on microscopy.
• Patients aged between 7 (to allow for blood sampling) 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.
• HIV negative status

Exclusion Criteria:

• Patients who have received any anti-leishmanial drugs in the last 6 months/ relapse cases.
• Patients with a negative lymph node/bone marrow (or spleen) smears.
• Patients with severe protein and or caloric malnutrition (Kwashiorkor or marasmus ; Adults: BMI </= 15, Children W/H<70, presence of oedema)
• Patients with previous history of hypersensitivity reaction to SSG or Amphotericin B.
• Patients suffering from a concomitant severe infection such as TB or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication.
• Patients suffering from other conditions associated with splenomegaly such as schistosomiasis.
• Patients with previous history of cardiac arrhythmia or an abnormal ECG
• Patients who are female of child bearing age (all females who have achieved menarche) / pregnant or lactating.
• Patients with haemoglobin < 5gm/dl.
• Patients with WBC < 1 x 10³/mm³.
• Patients with platelets < 40,000/mm³.
• Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
• Patients with serum creatinine outside the normal range for age and gender.
• Major surgical intervention within 2 weeks prior to enrolment.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amb+SSG; AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11	Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate; AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11
Experimental: Amb+Milt; AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11	Drug: Liposomal amphotericin B + miltefosine; AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11
Experimental: Milt; Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28	Drug: Miltefosine; Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Initial cure: proportion cured at Day 28	Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Final cure: proportion cured at day 210	6 months post treatment
Adverse events and serious adverse events occurring in the three study arms	up to day 60

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Collaborators: Gilead Sciences; Paladin Labs Inc.
• Investigators: Principal Investigator: Monique Wasunna, MD, Kenya Medical Research Institute

Publications and helpful links

General Publications

• Wasunna M, Njenga S, Balasegaram M, Alexander N, Omollo R, Edwards T, Dorlo TP, Musa B, Ali MH, Elamin MY, Kirigi G, Juma R, Kip AE, Schoone GJ, Hailu A, Olobo J, Ellis S, Kimutai R, Wells S, Khalil EA, Strub Wourgaft N, Alves F, Musa A. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial. PLoS Negl Trop Dis. 2016 Sep 14;10(9):e0004880. doi: 10.1371/journal.pntd.0004880. eCollection 2016 Sep.
• Allison A, Edwards T, Omollo R, Alves F, Magirr D, E Alexander ND. Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups. Trials. 2015 Nov 16;16:522. doi: 10.1186/s13063-015-1018-1.
• Omollo R, Alexander N, Edwards T, Khalil EA, Younis BM, Abuzaid AA, Wasunna M, Njoroge N, Kinoti D, Kirigi G, Dorlo TP, Ellis S, Balasegaram M, Musa AM. Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Jun 30;12:166. doi: 10.1186/1745-6215-12-166.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 10, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Actual): April 24, 2017
• Last Update Submitted That Met QC Criteria: April 21, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Phase II; Randomised clinical trial; Visceral Leishmaniasis
• 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; Antineoplastic Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Miltefosine; Amphotericin B; Liposomal amphotericin B; Antimony Sodium Gluconate
• Other Study ID Numbers: LEAP 0208

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study Protocol
   Information comments: Final Study Protocol