SCH708980 With and Without AmBisome for Visceral Leishmaniasis

NCT01437020 | Withdrawn Phase 1 DMC

• 1 other identifier: 11-I-N222
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Background: \- Visceral leishmaniasis (VL) is an infection caused by parasites carried by sand flies. The parasites cause fever, weight loss, and enlargement of the spleen and liver. They can also affect the blood and immune system. One possible treatment for VL involves an experimental drug called SCH708980, which may help to prevent the immune system from becoming suppressed and worsening the VL. Researchers want to give the drug along with AmBisome(Registered Trademark), which kills the parasites, to see if it is a safe and effective treatment. Objectives: \- To study the safety and effectiveness of SCH708980, alone and combined with AmBisome(Registered Trademark), as a treatment for visceral leishmaniasis. Eligibility:

• Individuals 18 to 60 years of who have been diagnosed with visceral leishmaniasis in the past 4 to 5 days, are HIV-negative, and are willing to stay in the hospital for 30 days.
• All participants will come from and be treated at the Kala-Azar Medical Research Center in Muzaffarpur, India. Design:
• This is a two-part study. Participants will be assigned to only one part of the study.
• Participants will be screened with a medical history and physical exam; blood, urine, and stool samples, spleen or bone marrow samples; spleen measurements; a chest xray; and a heart function test.
• Part 1 participants will be separated into two groups: a larger group will have a selected dose of the study drug followed by AmBisome 7 days later, and a smaller group will have a placebo treatment followed by AmBisome.
• Part 2 participants will have either the study drug or a placebo plus AmBisome, based on the test results from the Part 1 participants.
• All participants will be monitored in the hospital for 30 days, and will have the following tests:
• Regular blood samples
• Urine and stool samples (day 14)
• Spleen measurements (days 8, 14, 21, and 30)
• Spleen or bone marrow sample (day 30 only). Participants who still have VL symptoms will give another sample on day 45.
• At 6 months after the start of treatment, participants will have a follow-up visit with spleen measurements, blood and stool samples, and possible spleen or bone marrow samples

Conditions

Leishmaniasis; Effects of Immunotherapy

Keywords

IL-10; Leishmaniasis; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and tolerability of a single IV infusion of SCH708980 (0.3 mg/kg, 1.0 mg/kg, 3 mg/kg, or 10 mg/kg) over the initial 7 days and in combination with a single IV infusion of AmBisome® (10 mg/kg) on the 8th day in part 1 of the study

  Measured through Day 8

Secondary Outcomes (4)

• The anti-IL-10 parasitic effect, as measured by real-time polymerase chain reaction (RT-PCR)

  Measured 6 months after the start of treatment

• Serum concentrations of SCH708980

  Measured 6 months after the start of treatment

• Clinical response

  Measured 6 months after the start of treatment

• Outcomes at 6 months post-treatment

  Measured 6 months after the start of treatment

Study Arms (1)

Dose escalating-IV infusion of SCH708980 and Ambisome

EXPERIMENTAL

Drug: SCH708980 Anti-IL-10 monoclonal; Drug: AmBisome

Interventions

SCH708980 Anti-IL-10 monoclonal DRUG

Participants in Part 1 of the study will receive varying doses (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, or 10.0 mg/kg) of a single IV infusion of SCH708980. Participants in Part 2 of the study will receive a single IV infusion of SCH708980 on Day 1.

Dose escalating-IV infusion of SCH708980 and Ambisome

AmBisome DRUG

Participants in Part 1 of the study will receive a single IV infusion of AmBisome (10 mg/kg) 7 days after they receive SCH708980. Participants in Part 2 of the study will receive varying doses (3.75 mg/kg, 5 mg/kg, or 10 mg/kg) of a single IV infusion of AmBisome on Day 8.

Dose escalating-IV infusion of SCH708980 and Ambisome

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects (18 to 60 years of age) who meet the following criteria are eligible to enter the study:
• Newly diagnosed VL (within 4 to 5 days of screening) and confirmed by spleen or bone marrow aspirate.
• Clinical signs and symptoms compatible with VL: fever (\> 99 degrees F) over a 2-week duration, splenomegaly (palpable spleen below the costal margin), and weight loss.
• Biochemical and hematological test values:
• Hemoglobin \> 6.0g/100mL.
• WBC count \> 1.0 times 10(9)/L.
• Platelet count \> 40 times 10(9)/L.
• Aspartate aminotransferase (AST),alanine transaminase (ALT), and alkaline phosphatase \< 3 times the upper limit of normal.
• Prothrombin time (PT) \< 4 seconds above the control values.
• Serum creatinine levels within normal limits (males, 0.7 mg/dL - 1.1 mg/dL; females, 0.6 mg/dL - 0.9 mg/dL).
• Human immunodeficiency virus (HIV)-negative status.
• Willingness to be hospitalized for 30 days.
• Willingness to have samples stored.
• Negative serum pregnancy test result for women of childbearing potential.

You may not qualify if:

• A history of intercurrent or concurrent diseases (e.g., chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular, or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study.
• Any condition which, in the investigator's opinion, may prevent the subject from completing the study and the subsequent follow-up.
• Previous treatment for VL within 45 days of study enrollment.
• A history of allergy or hypersensitivity to amphotericin B.
• Prior treatment failures with amphotericin B.
• Current use of other drugs with known anti-leishmanial activity (e.g., antimonials, pentamidine, paromomycin, miltefosine), azoles (e.g., fluconazole, ketoconazole or itraconazole), nephrotoxic drugs, immunosuppressive drugs, other investigational agents, immunomodulatory drugs.
• Breastfeeding women
• Vaccinations within 30 days prior to enrollment in the study.
• Subjects younger than 18 years of age will be excluded from the study because insufficient data are available supporting dosing with SCH708980 in adults to judge the potential risk in children.
• Pregnant and lactating women are excluded from the study because insufficient data are available supporting dosing with SCH708980 in these populations to judge the potential risk.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Kala-Azar Medical Research Center (KAMRC), Rambag Road

Muzaffarpur, India

Location

Banaras Hindu University

Varanasi, India

Location

Related Publications (3)

• Desjeux P. Leishmaniasis. Public health aspects and control. Clin Dermatol. 1996 Sep-Oct;14(5):417-23. doi: 10.1016/0738-081x(96)00057-0. No abstract available.

  PMID: 8889319 BACKGROUND

• Addy M, Nandy A. Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in 24-Parganas? Bull World Health Organ. 1992;70(3):341-6.

  PMID: 1638662 BACKGROUND

• Bern C, Hightower AW, Chowdhury R, Ali M, Amann J, Wagatsuma Y, Haque R, Kurkjian K, Vaz LE, Begum M, Akter T, Cetre-Sossah CB, Ahluwalia IB, Dotson E, Secor WE, Breiman RF, Maguire JH. Risk factors for kala-azar in Bangladesh. Emerg Infect Dis. 2005 May;11(5):655-62. doi: 10.3201/eid1105.040718.

  PMID: 15890115 BACKGROUND

MeSH Terms

Conditions

Leishmaniasis

Interventions

liposomal amphotericin B

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Shyam Sundar, MD

  Institute of Medical Sciences, Banaras Hindu Universtiy, Varanasi, India

  PRINCIPAL INVESTIGATOR

• David Sacks, PhD

  Laboratory of Parasitic Diseases, NIAID, NIH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 20, 2011
• Last Updated: August 28, 2013

Record last verified: 2013-08

Locations

IN (2)