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Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1

NCT02124083 · Status: COMPLETED · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 12

Last updated 2018-02-22

Study results available
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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.

Conditions

  • Neimann-Pick Disease

Interventions

DRUG

Vorinostat

Histone deactylase inhibitor

Sponsors & Collaborators

  • Washington University School of Medicine

    collaborator OTHER

  • Weill Medical College of Cornell University

    collaborator OTHER

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    lead NIH

Principal Investigators

  • Forbes D Porter, M.D. · Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
60 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-04-25
Primary Completion
2016-12-13
Completion
2016-12-13
FDA Drug
Yes

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02124083 on ClinicalTrials.gov