SCH708980 With and Without AmBisome for Visceral Leishmaniasis
|First Submitted Date ICMJE||September 16, 2011|
|First Posted Date ICMJE||September 20, 2011|
|Last Update Posted Date||August 28, 2013|
|Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||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 [ Time Frame: Measured through Day 8 ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01437020 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||SCH708980 With and Without AmBisome for Visceral Leishmaniasis|
|Official Title ICMJE||A Phase I/II Clinical Trial To Assess the Safety and Biologic Activity of the Anti-IL-10 Monoclonal Antibody, SCH708980, in Combination With AmBisome(Registered Trademark), Versus That of Placebo in Combination With Ambisome(Registered Trademark), in Subjects With Visceral Leishmaniasis (VL)|
- 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.
- To study the safety and effectiveness of SCH708980, alone and combined with AmBisome(Registered Trademark), as a treatment for visceral leishmaniasis.
Visceral leishmaniasis (VL) or kala-azar is the most severe form of leishmaniasis, which can be fatal if left untreated. The majority of VL cases are found in resource-poor regions, including India (Bihar), Bangladesh, Brazil, Nepal, and Sudan. VL pathogenesis has been linked to an overproduction of the anti-inflammatory cytokine, interleukin (IL)-10, which can promote parasite replication and disease progression. Experimental models have shown that IL-10 plays a key role in the pathogenesis of VL.
The current study has two parts. Part 1 will be an open-label, dose-escalating design to determine the safety and tolerability of SCH708980 used in combination with AmBisome(Registered Trademark). Part 2 will be a randomized, single-blind, placebo-controlled, parallel design. A total of 50 subjects (n=10 subjects/group) will be enrolled in part 1 of the study. A group of 10 subjects will be observed for 7 days prior to receiving AmBisome(Registered Trademark) (10 mg/kg) on the 8th day, as part of the control group. Subsequently, 40 subjects (10 subjects/group) will receive a single intravenous (IV) infusion of SCH708980 (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, or 10 mg/kg) followed by a single IV infusion of AmBisome(Registered Trademark) (10 mg/kg) 7 days later. The first 2 subjects from each dose group to receive SCH708980 will be followed for 3 days after the drug is administered before treatment is initiated in the remaining 8 subjects in that group. Also, all individuals in each group will be followed for 7 days after AmBisome(Registered Trademark) is administered before the next higher dose-level group is enrolled in the study. Dose escalation will continue to the next dose level unless dose-limiting toxicities occur in > 20% of subjects in any cohort.
The dose level of SCH708980 to use in part 2 of the study will be decided 30 days after the start of AmBisome(Registered Trademark) treatment in the group receiving the highest dose in part 1. Randomization and accrual for part 2 of the study will begin at this time. The highest safe dose of SCH709890 (< 20% of subjects with dose-limiting toxicity) will be administered to subjects, not to exceed 10 mg/kg. Thirty subjects (n=10 subjects/group) will be randomized to 1:1:1 to receive:
SCH709890 and placebo will be administered over 60 minutes, while AmBisome(Registered Trademark) will be administered over 120 minutes.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: Dose escalating-IV infusion of SCH708980 and Ambisome
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Subjects (18 to 60 years of age) who meet the following criteria are eligible to enter the study:
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).
Exclusion of children:
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.
Exclusion of women:
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.
|Ages||18 Years to 60 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||India|
|Removed Location Countries|
|NCT Number ICMJE||NCT01437020|
|Other Study ID Numbers ICMJE||11-I-N222
11-I-N222 ( Other Identifier: NIH )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institute of Allergy and Infectious Diseases (NIAID)|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institute of Allergy and Infectious Diseases (NIAID)|
|Verification Date||August 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP