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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02534844
Registration number
NCT02534844
Ethics application status
Date submitted
18/08/2015
Date registered
28/08/2015
Date last updated
22/02/2023
Titles & IDs
Public title
VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease
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Scientific title
A Phase 2b/3 Prospective, Randomized, Double-Blind, Sham-Controlled 3-Part Trial of VTS-270 (2-hydroxypropyl-ß-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease
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Secondary ID [1]
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2015-002548-15
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Secondary ID [2]
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VTS301 (Parts A/B)
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Niemann-Pick Disease, Type C
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Condition category
Condition code
Neurological
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Neurodegenerative diseases
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Mental Health
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Other mental health disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Metabolic and Endocrine
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Metabolic disorders
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Neurological
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Other neurological disorders
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Metabolic and Endocrine
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Other metabolic disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Parts A/B: Adrabetadex
Other interventions - Parts A/B: Sham Control
Experimental: Parts A/B: Sham Control - Participants receive no study drug
Other: Parts A/B: Adrabetadex - Participants receive adrabetadex
Treatment: Drugs: Parts A/B: Adrabetadex
900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion
Other interventions: Parts A/B: Sham Control
No experimental drug is administered to participants - intrathecal administrations are simulated by skin prick
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 52
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Primary outcome [2]
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Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52
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Assessment method [2]
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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).
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Timepoint [2]
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Week 52
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Secondary outcome [1]
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Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 52
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Secondary outcome [2]
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Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52
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Assessment method [2]
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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.
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Timepoint [2]
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Week 52
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Secondary outcome [3]
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Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
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Assessment method [3]
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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.
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Timepoint [3]
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Week 52
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Secondary outcome [4]
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Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline, Week 52
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Secondary outcome [5]
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Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline up to Week 26
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Secondary outcome [6]
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Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline, Week 52
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Secondary outcome [7]
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Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline, Week 52
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Secondary outcome [8]
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Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite Score
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline up to Week 52
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Secondary outcome [9]
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Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
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Assessment method [9]
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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.
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Timepoint [9]
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Baseline, Week 52
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Secondary outcome [10]
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Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
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Assessment method [10]
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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.
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Timepoint [10]
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Baseline, Week 52
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Secondary outcome [11]
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Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline up to Week 52
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Secondary outcome [12]
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Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite Score
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Assessment method [12]
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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]).
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Timepoint [12]
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Baseline, Week 52
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Eligibility
Key inclusion criteria
Key
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
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Minimum age
4
Years
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Maximum age
21
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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-ß-cyclodextrin (HP-ß-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-ß-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-ß-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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2/Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/10/2015
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
28/03/2018
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Sample size
Target
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Accrual to date
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Final
56
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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The Prince of Wales Hospital - Sydney
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Recruitment hospital [2]
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Monash Medical Centre - Clayton
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Recruitment hospital [3]
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Royal Melbourne Hospital - Parkville
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Recruitment hospital [4]
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Royal Perth Hospital - Perth
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Recruitment postcode(s) [1]
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2031 - Sydney
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Recruitment postcode(s) [2]
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3168 - Clayton
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Recruitment postcode(s) [3]
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3050 - Parkville
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Recruitment postcode(s) [4]
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6000 - Perth
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Recruitment outside Australia
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United States of America
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Alabama
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California
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Colorado
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Florida
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Illinois
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Maryland
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Massachusetts
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New York
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North Carolina
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Pennsylvania
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Texas
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Washington
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France
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Cedex 12
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Germany
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Bochum
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Germany
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Mainz
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Germany
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Münster
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New Zealand
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Hamilton West
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Singapore
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Singapore
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Spain
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Barcelona
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Turkey
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Ankara
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United Kingdom
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West Midlands
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United Kingdom
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Mandos LLC
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02534844
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Clinical Study Lead
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Address
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Mandos LLC
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02534844
Download to PDF