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VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02534844
Recruitment Status : Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : July 29, 2021
Information provided by (Responsible Party):
Mandos LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Niemann-Pick Disease, Type C Drug: Parts A/B: Adrabetadex Other: Parts A/B: Sham Control Phase 2 Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
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)
Masking Description: While it is a double-blind trial, the participant and outcomes assessor will be blinded, as well as the Care Provider and Investigator.
Primary Purpose: Treatment
Official Title: A Phase 2b/3 Prospective, Randomized, Double-Blind, Sham-Controlled 3-Part Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease
Actual Study Start Date : October 2015
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Arm Intervention/treatment
Experimental: Parts A/B: Sham Control
Participants receive no study drug
Other: Parts A/B: Sham Control
No experimental drug is administered to patients - intrathecal administrations are simulated by skin prick
Other Names:
  • Procedure Control
  • Skin prick

Parts A/B: Adrabetadex
Participants receive adrabetadex
Drug: Parts A/B: Adrabetadex
900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion
Other Names:
  • 2-hydroxypropyl-β-cyclodextrin
  • Cyclodextrin
  • VTS-270
  • Adrabetadex

Primary Outcome Measures :
  1. Parts A/B: Composite Niemann Pick Type C Severity Scale (NPC-SS) [ Time Frame: Baseline, Week 52 ]
    Each of four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The highest (worst) possible score is 20.

  2. Parts A/ B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) [ Time Frame: Week 52 ]
    The study doctor rates his impression of the change in each participant's condition at week 52 on a scale from marked improvement (1) to marked worsening (7).

Secondary Outcome Measures :
  1. Parts A/B: NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response) at Baseline and Week 52 [ Time Frame: Baseline, Week 52 ]

    Each of four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The highest (worst) possible score is 20.

    The hearing domain and auditory brainstem response modifiers will be removed from the total NPC-SS total score for this measure.

  2. Parts A/ B: Number of Participants Classified as Responders by Their Caregiver at Week 52 [ Time Frame: Week 52 ]
    Caregiver rates the global impression of change at Week 52. Participants who receive the caregiver's rating of no change, minimally improved, moderately approved, or markedly improved will be classified as responders. The number of participants classified as responders will be recorded.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   4 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

Parts A/B:

  1. Had onset of neurological symptoms prior to 15 years of age
  2. Has confirmed diagnosis of NPC1 determined by either:

    1. two NPC1 mutations
    2. positive filipin staining and at least one NPC1 mutation
    3. vertical supranuclear gaze palsy (VSNGP) in combination with either: one NPC1 mutation, OR positive filipin staining or oxysterol levels consistent with NPC disease and no Niemann-Pick Type C2 (NPC2) Disease mutations
  3. Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
  4. Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
  5. Has an NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the following components: ambulation, fine motor skills, or swallowing; and has a score of 0 through 4 on the cognition component
  6. Has a total NPC Clinical Severity Scale Score of 10 or greater
  7. If taking miglustat, must have been on a stable dose for past 6-8 weeks and be willing to remain on a stable dose
  8. If participant has seizures, they have been adequately controlled for 3 months without changing dose or regimen
  9. Has agreed to discontinue all non-prescription supplements at least 1 month prior to first dose (Study Day 0)
  10. Has agreed to discontinue any other investigational treatments for NPC including vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0)
  11. If of child-bearing potential (not surgically sterile), agrees to use a medically acceptable method continuously, until at least 30 days after participation in the study

Key Exclusion Criteria:

  1. Has exclusion criteria as assessed by NPC Clinical Severity Scale:

    1. Unable to walk, wheelchair dependent (ambulation NPC score=5)
    2. Has need for a nasogastric tube to overcome swallowing difficulties (swallowing NPC score=5) unless used for supplemental feeding or administering medication
    3. severe dysmetria (fine motor score =5) or
    4. minimal cognitive function (cognition NPC score=5)
  2. Weighs less than 15 kg
  3. Has had prior treatment with intravenous 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for NPC1 disease, unless the subject has undergone a minimum 3-month washout period prior to Study Day 0, or has had any prior intrathecal (IT) administration of HP-β-CD
  4. Is taking antipsychotics for treatment of psychosis; use of antipsychotic medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity Disorder) will not exclude participation in this trial
  5. Has a history of hypersensitivity reactions to any product containing HP-β-CD
  6. Has a spinal deformity that could impact the ability to perform a lumbar puncture
  7. Has had a skin infection in the lumbar region within 2 months of study entry
  8. Has neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L
  9. Has thrombocytopenia (platelet count of less than 75 X 10^9/L)
  10. Has activated partial thromboplastin time (aPTT) or prothrombin time (PT) prolonged by > 1.5 times the upper limit of normal (ULN) or known history of a bleeding disorder
  11. Has had status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified
  12. Has evidence of either obstructive hydrocephalus or normal pressure hydrocephalus
  13. Has recently used anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
  14. Is unable to comply with the study procedures or has a clinical disease or laboratory abnormality that in the opinion of the investigator would potentially increase the risk of participation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02534844

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Sponsors and Collaborators
Mandos LLC
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Study Director: Clinical Study Lead Mandos LLC
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Responsible Party: Mandos LLC
ClinicalTrials.gov Identifier: NCT02534844    
Other Study ID Numbers: VTS301 (Parts A/B)
2015-002548-15 ( EudraCT Number )
First Posted: August 28, 2015    Key Record Dates
Last Update Posted: July 29, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT02534844) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mandos LLC:
Niemann-Pick Type C1 (NPC1) Disease
neurologic disease
gross motor dysfunction
fine motor dysfunction
swallowing problems
cognitive dysfunction
gait abnormalities
Additional relevant MeSH terms:
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Pick Disease of the Brain
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Frontotemporal Dementia
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lipid Metabolism Disorders