VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease
Condition: Niemann-Pick Disease, Type C
MeSH terms: Pick Disease of the Brain; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Due to different study designs, the sponsor separated Part C into a separate registration
      (NCT04958642), leaving Parts A/B here in NCT02534844.

      This study is to find out how safe and effective VTS-270 is for patients with Niemann-Pick
      Type C1 (NPC1) disease who have neurologic symptoms (listed under Keywords).

      In Parts A/B, two out of every three patients will receive the study drug. The third patient
      will receive 1 to 2 small needle pricks at the location where the LP and IT injection is
      normally made (sham control).

      In Part C, all participants will receive study drug, as described in the Part C registration
      record.

      Start date for this record is the first day a participant was enrolled in Parts A/B. The
      trial is actually continuing until the last primary outcome measure of safety data are
      collected from Part C participants. The last primary outcome measure of safety, along with
      final adverse events results will be posted in the separate Part C registration record.
    

Detailed description: 
      Non-clinical studies and a Phase 1 clinical trial suggest that intrathecal administration of
      VTS-270 in patients with neurologic manifestations of Niemann-Pick Type C1 (NPC1) disease has
      the potential to slow the rate of progression of their neurologic disease.

      Niemann-Pick Type C1 (NPC1) disease is a rare, neurodegenerative, inherited, autosomal
      recessive lysosomal lipid storage disorder primarily in children and teenagers. The disease
      is characterized by the inability to properly metabolize cholesterol and other lipids within
      the cell due to mutations in the NPC1 gene, causing unesterified cholesterol to accumulate in
      the brain, liver and spleen.

      This study plans to enroll about 51 participants with NPC1 disease. It will be conducted in
      three parts: Parts A, B, and C.

        -  Part A will evaluate 3 different dose levels of VTS-270 in 12 participants to determine
           the dose level for Parts B and C.

        -  In Part B, 39 more participants will join the original 12 to evaluate the safety and
           effectiveness of the dose selected from Part A compared to sham control.

        -  Part C will be an open-label extension phase of the study for Part B participants who
           either complete Part B or have met rescue therapy criteria, as well as participants
           entering Part C from other trials.

      Participants in Part C will receive treatment with VTS-270 until the product is licensed or
      the program is terminated (anticipated within 5 years).

      Final results will be posted in the Part C registration record (NCT04958642).
    

Intervention name(s): Parts A/B: Adrabetadex; Parts A/B: Sham Control
Intervention type(s): Drug; Other
Intervention description(s): 900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion; No experimental drug is administered to participants - intrathecal administrations are simulated by skin prick
Other intervention name(s): 2-hydroxypropyl-β-cyclodextrin; Cyclodextrin; VTS-270; Adrabetadex; Procedure Control; Skin prick
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: In Parts A/B (see other registration for Part C description)
Masking: Double (Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Niemann-Pick Type C1 (NPC1) Disease; neurologic disease; gross motor dysfunction; fine motor dysfunction; dysphagia; swallowing problems; cognitive dysfunction; gait abnormalities; pediatrics