VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease | NCT02534844 | Trialant
NCT02534844
Sponsor
Mandos LLC
Status
Completed
Last Update Posted
Feb 22, 2023Actual
Enrollment
56Actual
Phase
Phase 2Phase 3
Conditions
Niemann-Pick Disease, Type C
Interventions
Parts A/B: Adrabetadex
Parts A/B: Sham Control
Countries
United States
Australia
France
Germany
New Zealand
Singapore
Spain
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02534844
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
VTS301 (Parts A/B)
Secondary IDs
ID
Type
Description
Link
2015-002548-15
EudraCT Number
Brief Title
VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease
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
Acronym
Not provided
Organization
Mandos LLCINDUSTRY
Status Module
Record Verification Date
Feb 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 2015Actual
Primary Completion Date
Mar 28, 2018Actual
Completion Date
Mar 28, 2018Actual
First Submitted Date
Aug 18, 2015
First Submission Date that Met QC Criteria
Aug 27, 2015
First Posted Date
Aug 28, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 11, 2022
Results First Submitted that Met QC Criteria
Feb 20, 2023
Results First Posted Date
Feb 22, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 20, 2023
Last Update Posted Date
Feb 22, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Mandos LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
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).
Conditions Module
Conditions
Niemann-Pick Disease, Type C
Keywords
Niemann-Pick Type C1 (NPC1) Disease
neurologic disease
gross motor dysfunction
fine motor dysfunction
dysphagia
swallowing problems
cognitive dysfunction
gait abnormalities
pediatrics
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
56Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Parts A/B: Sham Control
Experimental
Participants receive no study drug
Other: Parts A/B: Sham Control
Parts A/B: Adrabetadex
Other
Participants receive adrabetadex
Drug: Parts A/B: Adrabetadex
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Parts A/B: Adrabetadex
Drug
900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion
Parts A/B: Adrabetadex
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
Measure
Description
Time Frame
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and auditory brainstem response modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual component scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
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
Key Exclusion Criteria:
Has exclusion criteria as assessed by NPC Clinical Severity Scale:
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
Has recently used anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
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
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.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
No
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.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: Adrabetadex 900 mg
Participants received 4 lumbar intrathecal (IT) infusions of adrabetadex 900 milligrams (mg) once every 2 weeks.
FG001
Part A: Adrabetadex 1200 mg
Periods
Title
Milestones
Reasons Not Completed
Part A
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Oct 18, 2019
Nov 1, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
In Parts A/B (see other registration for Part C description)
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
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.
Who Masked
Care ProviderInvestigator
2-hydroxypropyl-β-cyclodextrin
Cyclodextrin
VTS-270
Adrabetadex
Parts A/B: Sham Control
Other
No experimental drug is administered to participants - intrathecal administrations are simulated by skin prick
Parts A/B: Sham Control
Procedure Control
Skin prick
Baseline, Week 52
Parts A/ B: Number of Participants Classified as CGIC Responders 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). CGIC Responders are defined as participants who received the caregiver's rating of no change, minimally improved, moderately improved, or markedly improved from baseline to 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
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and ABR modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment. Responders on NPC-SS Total Score are defined as participants with no change or improvement on NPC-SS total score from baseline to 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
The EQ-5D-3L assessment is a self-reported, simple, descriptive system measuring 5 dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranges from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
Baseline, Week 52
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Participants who manifested significant disease progression according to predefined clinical criteria after treatment of 26 weeks or more had the option to rescue. Number of participants who qualified for the rescue option following a minimum of 26 weeks of treatment were analyzed.
Baseline up to Week 26
Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse) with higher scores indicating more severe clinical impairment.
Baseline, Week 52
Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 45 (worst), with higher scores indicating more severe clinical impairment.
Baseline, Week 52
Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite 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. The product-limit survival analysis method is used to estimate the time to one point increase (worsening) in NPC-SS composite score. Time to worsening in NPC-SS Composite Score defined as the interval from study drug administration to a one point increase in the NPC-SS composite score. If a subject discontinued from the study prior to Week 52, then the subject was censored at time of discontinuation. If a subject completed the Week 52 visit, then the subject was censored at the time of last study visit.
Baseline up to Week 52
Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
The TUG is a test of balance and risk for falls. This test measures the time taken by a participant to walk 3 meters starting from a sitting position and it ends when the participant is seated again.
Baseline, Week 52
Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
The 9-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded.
Baseline, Week 52
Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event (AE) with onset on or after start of study Drug. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Baseline up to Week 52
Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite 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. The Annualized rate of change (Slope) is calculated as 365.25 *([measurement at post-baseline visit - measurement at baseline]/[date of post-baseline visit - date of baseline visit + 1]).
Baseline, Week 52
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
Participants received 4 lumbar IT infusions of adrabetadex 1200 mg once every 2 weeks.
FG002
Part A: Adrabetadex 1800 mg
Participants received 4 lumbar IT infusions of adrabetadex 1800 mg once every 2 weeks.
FG003
Part A: Sham Control
Participants received sham control procedures once every 2 weeks.
FG004
Part B: Adrabetadex 900 mg
Participants received lumbar IT infusions of adrabetadex 900 mg once every 2 weeks.
FG005
Part B: Sham Control
Participants received sham control procedures once every 2 weeks.
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
Received at Least One Dose of Study Drug
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Part B
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00429 subjects
FG00515 subjects
Received at Least One Dose of Study Drug
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Intent-to-treat (ITT) population was defined as all randomized participants. As per planned analysis, baseline characteristics data were collected and presented by participants' overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
BG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00018
BG00138
BG00256
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00011.7± 5.10
BG00112.7± 5.64
BG00212.4± 5.45
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00010
BG00116
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0003
BG0013
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Modified intent-to-treat (mITT) population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Units
Counts
Participants
OG00018
OG00138
Title
Denominators
Categories
Baseline
ParticipantsOG00018
ParticipantsOG00136
Title
Measurements
OG0008.1± 4.27
Primary
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).
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Posted
Count of Participants
Participants
Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Secondary
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and auditory brainstem response modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual component scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment.
mITT population included all randomized participants who received at least one treatment. As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Secondary
Parts A/ B: Number of Participants Classified as CGIC Responders 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). CGIC Responders are defined as participants who received the caregiver's rating of no change, minimally improved, moderately improved, or markedly improved from baseline to Week 52.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Posted
Count of Participants
Participants
Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks..
Secondary
Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and ABR modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment. Responders on NPC-SS Total Score are defined as participants with no change or improvement on NPC-SS total score from baseline to Week 52.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Posted
Count of Participants
Participants
Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Secondary
Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
The EQ-5D-3L assessment is a self-reported, simple, descriptive system measuring 5 dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranges from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
mITT population included all randomized participants who received at least one treatment. As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure. Number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Secondary
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Participants who manifested significant disease progression according to predefined clinical criteria after treatment of 26 weeks or more had the option to rescue. Number of participants who qualified for the rescue option following a minimum of 26 weeks of treatment were analyzed.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Posted
Count of Participants
Participants
Baseline up to Week 26
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Units
Counts
Participants
Secondary
Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse) with higher scores indicating more severe clinical impairment.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, Number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Units
Counts
Secondary
Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 45 (worst), with higher scores indicating more severe clinical impairment.
mITT population included all randomized participants who received at least one treatment). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure, and number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Secondary
Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite 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. The product-limit survival analysis method is used to estimate the time to one point increase (worsening) in NPC-SS composite score. Time to worsening in NPC-SS Composite Score defined as the interval from study drug administration to a one point increase in the NPC-SS composite score. If a subject discontinued from the study prior to Week 52, then the subject was censored at time of discontinuation. If a subject completed the Week 52 visit, then the subject was censored at the time of last study visit.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study.
Posted
Median
95% Confidence Interval
Days
Baseline up to Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Secondary
Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
The TUG is a test of balance and risk for falls. This test measures the time taken by a participant to walk 3 meters starting from a sitting position and it ends when the participant is seated again.
mITT population included all randomized participants who received at least one treatment. As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure, and number analyzed = participants evaluable at specified time-point.
Posted
Mean
Standard Deviation
seconds
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Units
Counts
Participants
Secondary
Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
The 9-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded.
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
seconds
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Units
Counts
Secondary
Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event (AE) with onset on or after start of study Drug. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Safety population was defined as all randomized participants who received at least 1 procedure (adrabetadex infusion via LP or sham).
Posted
Count of Participants
Participants
Baseline up to Week 52
ID
Title
Description
OG000
Part A: Adrabetadex 900 mg
Participants received 4 lumbar IT infusions of adrabetadex 900 mg once every 2 weeks.
OG001
Part A: Adrabetadex 1200 mg
Participants received 4 lumbar IT infusions of adrabetadex 1200 mg once every 2 weeks.
OG002
Part A: Adrabetadex 1800 mg
Participants received 4 lumbar IT infusions of adrabetadex 1800 mg once every 2 weeks.
OG003
Part A: Sham Control
Secondary
Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite 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. The Annualized rate of change (Slope) is calculated as 365.25 *([measurement at post-baseline visit - measurement at baseline]/[date of post-baseline visit - date of baseline visit + 1]).
mITT population included all randomized participants who received at least one treatment (sham or adrabetadex). As per planned analysis, efficacy data were collected and presented by overall randomized treatment assignment (either sham or adrabetadex). These two treatment arms (either sham or adrabetadex) combine data from Parts A and B of the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
score on NPC-SS scale/year
Baseline, Week 52
ID
Title
Description
OG000
Sham Control
Participants received sham control procedures once every 2 weeks for a total of 52 weeks.
OG001
Adrabetadex
Participants received lumbar IT infusions of adrabetadex once every 2 weeks for a total of 52 weeks.
Time Frame
Baseline up to Week 52
Description
Safety population was defined as all randomized participants who received at least 1 procedure (adrabetadex infusion via LP or sham).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: Adrabetadex 900 mg
Participants received 4 lumbar IT infusions of adrabetadex 900 mg once every 2 weeks.
0
3
1
3
3
3
EG001
Part A: Adrabetadex 1200 mg
Participants received 4 lumbar IT infusions of adrabetadex 1200 mg once every 2 weeks.
0
3
0
3
3
3
EG002
Part A: Adrabetadex 1800 mg
Participants received 4 lumbar IT infusions of adrabetadex 1800 mg once every 2 weeks.
1
3
2
3
3
3
EG003
Part A: Sham Control
Participants received sham control procedures once every 2 weeks.
0
3
0
3
3
3
EG004
Part B: Adrabetadex 900 mg
Participants received lumbar IT infusions of adrabetadex 900 mg once every 2 weeks.
0
29
16
29
28
29
EG005
Part B: Sham Control
Participants received sham control procedures once every 2 weeks.