Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1
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ClinicalTrials.gov Identifier: NCT02124083 |
Recruitment Status :
Completed
First Posted : April 28, 2014
Results First Posted : February 22, 2018
Last Update Posted : February 22, 2018
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Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators:
Washington University School of Medicine
Weill Medical College of Cornell University
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
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Tracking Information | |||||
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First Submitted Date ICMJE | April 25, 2014 | ||||
First Posted Date ICMJE | April 28, 2014 | ||||
Results First Submitted Date ICMJE | December 12, 2017 | ||||
Results First Posted Date ICMJE | February 22, 2018 | ||||
Last Update Posted Date | February 22, 2018 | ||||
Study Start Date ICMJE | April 25, 2014 | ||||
Actual Primary Completion Date | December 13, 2016 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
To assess the safety and tolerability of oral Vorinostat therapy in Niemann-Pick Disease, type C1 [ Time Frame: 6 months ] | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
To obtain pilot data on Plasma and cerebrospinal fluid biomarkers and on Potential clinical endpoints [ Time Frame: 6 months ] | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 | ||||
Official Title ICMJE | Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 | ||||
Brief Summary | Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). Vorinostat is a histone deacetylase inhibitor that has been shown in vivo to increase mutant NPC1 protein levels and to reverse cellular accumulation of unesterified cholesterol. Vorinostat has been labeled by the FDA for treatment of cutaneous T-cell lymphoma. In this Phase I, non-randomized, open-label, single-center study, we plan to study whether Vorinostat can be repurposed to treat patients with NPC1. Our primary objective is to determine the safety and tolerability of Vorinostat in NPC1 disease. Our secondary objectives will be to determine biochemical efficacy of Vorinostat to increase expression of NPC1 protein and normalize lipid and protein biomarkers. This study will enroll up to 12 NPC1 patients and test the safety of two dose levels (200 and 400 mg). Drug will be administered on a 3 days on/4 days off schedule for 3 months at each dose level. Patients will be evaluated at the NIH Clinical Center at 0, 3 and 6 months. Safety will be assessed by adverse events (AEs), clinical laboratory tests and physical examinations. Biochemical efficacy will be assessed by measurement of serum and cerebral spinal fluid biomarkers. Clinical efficacy will be evaluated by audiologic testing, assessment ataxia, and swallowing studies. | ||||
Detailed Description | Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). Vorinostat is a histone deacetylase inhibitor that has been shown in vivo to increase mutant NPC1 protein levels and to reverse cellular accumulation of unesterified cholesterol. Vorinostat has been labeled by the FDA for treatment of cutaneous T-cell lymphoma. In this Phase I, non-randomized, open-label, single-center study, we plan to study whether Vorinostat can be repurposed to treat patients with NPC1. Our primary objective is to determine the safety and tolerability of Vorinostat in NPC1 disease. Our secondary objectives will be to determine biochemical efficacy of Vorinostat to increase expression of NPC1 protein and normalize lipid and protein biomarkers. This study will enroll up to 12 NPC1 patients and test the safety of two dose levels (200 and 400 mg). Drug will be administered on a 3 days on/4 days off schedule for 3 months at each dose level. Patients will be evaluated at the NIH Clinical Center at 0, 3 and 6 months. Safety will be assessed by adverse events (AEs), clinical laboratory tests and physical examinations. Biochemical efficacy will be assessed by measurement of serum and cerebral spinal fluid biomarkers. Clinical efficacy will be evaluated by audiologic testing, assessment ataxia, and swallowing studies. | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Neimann-Pick Disease | ||||
Intervention ICMJE | Drug: Vorinostat
Histone deactylase inhibitor
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Study Arms ICMJE | Experimental: Vorinostat
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
Intervention: Drug: Vorinostat
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
12 | ||||
Original Estimated Enrollment ICMJE |
15 | ||||
Actual Study Completion Date ICMJE | December 13, 2016 | ||||
Actual Primary Completion Date | December 13, 2016 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | -INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 60 Years (Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02124083 | ||||
Other Study ID Numbers ICMJE | 140102 14-CH-0102 ( Other Identifier: The National Institutes of Health ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ) | ||||
Study Sponsor ICMJE | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | January 13, 2018 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |