Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
2015-002548-15
Secondary ID [2] 0 0
VTS301 (Parts A/B)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Niemann-Pick Disease, Type C 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Mental Health 0 0 0 0
Other mental health disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score
Timepoint [1] 0 0
Baseline, Week 52
Primary outcome [2] 0 0
Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [1] 0 0
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Timepoint [5] 0 0
Baseline up to Week 26
Secondary outcome [6] 0 0
Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [7] 0 0
Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite Score
Timepoint [8] 0 0
Baseline up to Week 52
Secondary outcome [9] 0 0
Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
Timepoint [9] 0 0
Baseline, Week 52
Secondary outcome [10] 0 0
Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
Timepoint [10] 0 0
Baseline, Week 52
Secondary outcome [11] 0 0
Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [11] 0 0
Baseline up to Week 52
Secondary outcome [12] 0 0
Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite Score
Timepoint [12] 0 0
Baseline, Week 52

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
Minimum age
4 Years
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/03/2018
Sample size
Target
Accrual to date
Final
56
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
The Prince of Wales Hospital - Sydney
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
France
State/province [13] 0 0
Cedex 12
Country [14] 0 0
Germany
State/province [14] 0 0
Bochum
Country [15] 0 0
Germany
State/province [15] 0 0
Mainz
Country [16] 0 0
Germany
State/province [16] 0 0
Münster
Country [17] 0 0
New Zealand
State/province [17] 0 0
Hamilton West
Country [18] 0 0
Singapore
State/province [18] 0 0
Singapore
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Turkey
State/province [20] 0 0
Ankara
Country [21] 0 0
United Kingdom
State/province [21] 0 0
West Midlands
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Mandos LLC
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT02534844
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Study Lead
Address 0 0
Mandos LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02534844