VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease
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
2 other identifiers
interventional
56
9 countries
29
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2015
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 18, 2015
CompletedFirst Posted
Study publicly available on registry
August 28, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 28, 2018
CompletedResults Posted
Study results publicly available
February 22, 2023
CompletedFebruary 22, 2023
February 1, 2023
2.5 years
August 18, 2015
November 11, 2022
February 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score
The NPC-SS composite score is the sum of the ambulation, cognition, fine motor, and swallowing domains of the NPC-SS. Each of the four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The total score was the sum of individual components scores which ranges from 0 (best) to 20 (worst), with higher scores indicating more severe clinical impairment.
Baseline, Week 52
Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52
The Clinician CGIC is a 7-point Likert scale. The scale requires assessment of change from a baseline level of disease activity, with anchors ranging from markedly improved, moderately improved, and minimally improved to no change and corresponding worsening (minimally, moderately, markedly). The Investigator rates his/her impression of the change in each participant's condition at week 52 on a scale from marked improvement (1) to marked worsening (7).
Week 52
Secondary Outcomes (12)
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
Baseline, Week 52
Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52
Week 52
Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
Week 52
Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
Baseline, Week 52
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Baseline up to Week 26
- +7 more secondary outcomes
Study Arms (2)
Parts A/B: Sham Control
EXPERIMENTALParticipants receive no study drug
Parts A/B: Adrabetadex
OTHERParticipants receive adrabetadex
Interventions
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
Eligibility Criteria
You may qualify if:
- Parts A/B:
- Had onset of neurological symptoms prior to 15 years of age
- Has confirmed diagnosis of NPC1 determined by either:
- two NPC1 mutations
- positive filipin staining and at least one NPC1 mutation
- 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
- Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
- Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
- 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
- Has a total NPC Clinical Severity Scale Score of 10 or greater
- If taking miglustat, must have been on a stable dose for past 6-8 weeks and be willing to remain on a stable dose
- If participant has seizures, they have been adequately controlled for 3 months without changing dose or regimen
- Has agreed to discontinue all non-prescription supplements at least 1 month prior to first dose (Study Day 0)
- 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)
- 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
You may not qualify if:
- Unable to walk, wheelchair dependent (ambulation NPC score=5)
- Has need for a nasogastric tube to overcome swallowing difficulties (swallowing NPC score=5) unless used for supplemental feeding or administering medication
- severe dysmetria (fine motor score =5) or
- minimal cognitive function (cognition NPC score=5)
- Weighs less than 15 kg
- 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
- 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
- Has a history of hypersensitivity reactions to any product containing HP-β-CD
- Has a spinal deformity that could impact the ability to perform a lumbar puncture
- Has had a skin infection in the lumbar region within 2 months of study entry
- Has neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10\^9/L
- Has thrombocytopenia (platelet count of less than 75 X 10\^9/L)
- 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
- Has had status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified
- Has evidence of either obstructive hydrocephalus or normal pressure hydrocephalus
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mandos LLClead
Study Sites (29)
University of Alabama at Birmingham
Birmingham, Alabama, 35223, United States
Children's Hospital of Orange County
Orange, California, 92867, United States
University of California San Francisco
San Francisco, California, 94143-0780, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Shands Children's Hospital
Gainesville, Florida, 32608, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Bethesda, Maryland, 20892-2425, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
University of North Carolina
Chapel Hill, North Carolina, 27514, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18101, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Multicare Institute for Research and Innovation
Tacoma, Washington, 98405, United States
The Prince of Wales Hospital
Sydney, New South Wales, 2031, Australia
Monash Medical Centre
Clayton, Victoria, 3168, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Royal Perth Hospital
Perth, Western Australia, 6000, Australia
CHU Paris Est - Hospital d'Enfants Armand-Trousseau
Paris, Cedex 12, 75 571, France
Katholisches Klinikim Bochum gGmbH
Bochum, 44791, Germany
Universitaetsklinikum Mainz
Mainz, 55131, Germany
Universitaetsklinikum Muenster
Münster, 48149, Germany
Waikato Hospital
Hamilton West, 3204, New Zealand
National University Hospital (Singapore) Pte, Ltd
Singapore, 119074, Singapore
Hospital Universitario del Valle Hebron
Barcelona, 08035, Spain
Hacettepe University Medical Faculty
Altındağ, Ankara, 06230, Turkey (Türkiye)
Gazi University Medical Faculty
Çankaya, Ankara, 06570, Turkey (Türkiye)
Birmingham Women's and Children's NHS Trust
Birmingham, West Midlands, B4 6NH, United Kingdom
Great Ormond Street Hospital
London, WC1N 3JH, United Kingdom
Related Publications (1)
Farmer C, Lewis M, Farhat N, Robbins KP, Joseph L, Albert OK, Bianconi S, Hoffmann A, Giserman-Kiss I, Alexander DM, Thurm A, Porter FD, Kravis EB. Convergent Validity of the Fine Motor, Speech, and Cognitive Domains of the 5-Domain Niemann-Pick Disease Type C Clinical Severity Scale. J Child Neurol. 2026 Jan;41(1):43-53. doi: 10.1177/08830738251346348. Epub 2025 Jun 17.
PMID: 40525490DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Executive Vice President, Regulatory Affairs
- Organization
- Mandos, LLC
Study Officials
- STUDY DIRECTOR
Clinical Study Lead
Mandos LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- CARE PROVIDER, INVESTIGATOR
- Masking Details
- While it is a double-blind trial, the participant and outcomes assessor will be blinded, as well as the Care Provider and Investigator.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 18, 2015
First Posted
August 28, 2015
Study Start
October 1, 2015
Primary Completion
March 28, 2018
Study Completion
March 28, 2018
Last Updated
February 22, 2023
Results First Posted
February 22, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will not share
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.