Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease
Condition: Niemann-Pick Disease, Type C1
MeSH terms: Pick Disease of the Brain; Aphasia, Primary Progressive; Frontotemporal Dementia; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Hydroxypropyl beta cyclodextrin (HPBCD) is being tested for a disease called Niemann-Pick
      disease type C1 (NPC1). NPC1 is a genetic disorder that results in gradual loss of nervous
      system function. Cholesterol and other fats have trouble moving out of the brain cells, which
      makes the cells work poorly and leads to symptoms. There is no treatment currently approved
      in the US for NPC1. Researchers want to test if it is safe to use HPBCD for NPC1. They want
      to see if it can help brain cells process cholesterol better.

      Objectives:

      - To test the safety and effectiveness of HPBCD for NPC1.

      Eligibility:

      - Individuals between 2 and 25 years of age who have been diagnosed with NPC1 and who have
      not already received HPBCD in an attempt to treat NPC1.

      Design:

        -  Participants will be screened with a physical exam and medical history. They will
           provide blood and urine samples for screening. They will also have neurological tests,
           including tests of hearing, speech and movement.

        -  Participants will have a lumbar puncture (also called a spinal tap) every month to
           deliver the drug to the spinal fluid that surrounds the brain. The length of the trial
           will be determined by the safety and efficacy information that is obtained.

        -  Treatment will be monitored with frequent blood and urine tests, cerebral spinal fluid
           tests, hearing and neurological exams.
    

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). The National Institutes of Health (NIH) Therapeutics for Rare and
      Neglected Diseases (TRND) program is developing 2-hydroxypropyl-Beta-cyclodextrin
      (HP-Beta-CD) for the treatment of patients with Niemann-Pick disease type C1 (NPC1) to slow
      progression of symptoms of the disease. In this Phase 1, non-randomized, open-label,
      single-center, study, we propose to administer HP-Beta-CD intrathecally via lumbar injection
      to drug naive cohorts of 3 patients at doses of 200 mg escalated to 300, 400 mg and 900 mg.
      Subsequent dose escalations may occur in increments of up to 300 mg. The objectives of this
      study are to assess the safety, tolerability, feasibility, and pharmacokinetics (PK) of
      intrathecally (IT) administered HP-Beta-CD to NPC1 patients, to determine an active dose of
      HP-Beta-CD as measured by changes in plasma 24-(S) hydroxycholesterol (24(S)-HC)
      concentration, and to evaluate the use of biomarkers and potential clinical outcomes of NPC1.
      All patients in the cohort will receive HP-Beta-CD (n = 3) once monthly for at least two
      doses, and the decision to dose-escalate will be based on safety and on biochemical data.
      Safety will be assessed by adverse events (AEs), audiologic evaluation, clinical laboratory
      tests, vital signs, physical examinations, chest X-rays and electrocardiograms (ECGs).
      Biochemical efficacy will be measured by change from baseline in plasma 24(S)-HC. PK will be
      assessed for plasma HP-Beta-CD.
    

Intervention name(s): VTS-270
Intervention type(s): Drug
Other intervention name(s): 2-hydroxypropyl-beta-cyclodextrin
Intervention MeSH terms: Betadex
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 2-Hydroxypropyl-B-Cyclodextrin; Niemann-Pick Disease, Type C1; Neurodegeneration