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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02534844




Registration number
NCT02534844
Ethics application status
Date submitted
18/08/2015
Date registered
28/08/2015
Date last updated
3/03/2021

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
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 - VTS-270
Other interventions - Sham

Experimental: Part A- 900 mg VTS-270 - Participants receive 900 milligram (mg) of VTS-270 administered by the lumbar intrathecal (IT) route every 2 weeks.

Experimental: Part A- 1200 mg VTS-270 - Participants receive 1200 mg of VTS-270 administered by the lumbar IT route every 2 weeks.

Experimental: Part A- 1800 mg VTS-270 - Participants receive 1800 mg of VTS-270 administered by the lumbar IT route every 2 weeks.

Other: Part A- Sham - Participants receive 1 to 2 skin pricks with a needle.

Experimental: Part B- 900 mg VTS-270 - Participants receive 900 mg of VTS-270 administered by the lumbar IT route every 2 weeks.

Other: Part B- Sham - Participants receive 1 to 2 skin pricks with a needle.

Experimental: Part C- 900 mg VTS-270 - Participants receive 900 mg of VTS-270 administered by the lumbar IT route every 2 weeks.


Treatment: Drugs: VTS-270
Lumbar intrathecal infusion of VTS-270

Other interventions: Sham
No experimental drug is administered to patients. All 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
Part A: Number of participants with adverse events (AE)
Timepoint [1] 0 0
within 8 weeks
Primary outcome [2] 0 0
Part A: Composite Niemann Pick Type C Severity Scale (NPC-SS) at Week 8 - Each of four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The highest (worst) possible score is 20.
Timepoint [2] 0 0
Week 8
Primary outcome [3] 0 0
Part A: Blinded Clinician Global Impression of Change (Clinician-CGIC) at Week 8 - The Clinician-CGIC will be conducted at the beginning of the 8-week visit prior to all other procedures and assessments. After the screening (baseline) assessment, the blinded rater will have no access to or knowledge of treatment assignment, clinical and laboratory AEs, laboratory tests, and any of the other assessments. The Clinician-CGIC is evaluated using a 7-point Likert scale ranging from 1 (marked improvement from screening) to 7 (marked worsening from screening), will be assessed Week 8 for Part A. The same rater should conduct the Clinician-CGIC at all visits for a given participant throughout the entire trial.
Timepoint [3] 0 0
at Week 8
Primary outcome [4] 0 0
Part B: Composite Niemann Pick Type C Severity Scale (NPC-SS) During Part B - Each of four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The highest (worst) possible score is 20.
Timepoint [4] 0 0
at Week 52
Primary outcome [5] 0 0
Part B: Blinded Clinician-CGIC - The Clinician-CGIC, evaluated using a 7-point Likert scale ranging from 1 (marked improvement) from screening to 7 (marked worsening from screening), will be assessed at Weeks 16, 24, 32, 40, 46, and 52 in Part B, plus at Follow-up Weeks 63 and 76 in Part B for subjects who elect not to participate in Part C.
Timepoint [5] 0 0
within 76 weeks
Primary outcome [6] 0 0
Part C: Blinded Clinician-CGIC - For Part C, the Clinician-CGIC will be conducted every 6 months, at the end of study visit or end of treatment, and at follow-up visits 2 and 3, using a 7-point Likert scale ranging from 1 (marked improvement from screening) to 7 (marked worsening from screening).
Timepoint [6] 0 0
anticipated within 6 years of study start
Secondary outcome [1] 0 0
Part B: Clinician and Caregiver Global Impression of Change
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Part B: Time to get up and go test
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Part B: 9-hole peg test
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Part B: Percentage of patients with clinical worsening
Timepoint [4] 0 0
from week 26 through week 52 based on first dose being week 1
Secondary outcome [5] 0 0
Part B: European Quality of Life-5 Dimensions Quality of Life Rating (EQ-5D QoL)
Timepoint [5] 0 0
52 weeks

Eligibility
Key inclusion criteria
Key

Parts A and B:

1. Onset of neurological symptoms prior to 15 years of age.

2. Confirmed diagnosis of NPC1 determined by either:

- Two NPC1 mutations;

- Positive filipin staining and at least one NPC1 mutation;

- c. 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. Subject or parent/guardian must provide written informed consent and assent (for
minors).

4. Ability to undergo a lumbar puncture (LP) and IT drug administration under conscious
sedation or general anesthesia.

5. An NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the
following on the NPC Severity Scale components: ambulation, fine motor skills, or
swallowing and a score of 0 through 4 on the cognition component.

6. Total NPC Clinical Severity Scale Score of 10 or greater.

7. If taking miglustat, must have been on a stable dose for past 3 months and be willing
to remain on a stable dose.

8. Subjects with adequately controlled seizures may qualify for enrollment. Subjects with
a history of seizures should have a stable pattern of seizure activity and be on a
stable dose and regimen of anti epileptic medication during the 3 months prior to
screening without change in dose in regimen up to and including Study Day 0.

9. Agree to discontinue all non-prescription supplements such as Coenzyme Q10, curcumin,
cinnamon, fish oil supplements, high dose vitamin D (>500 milli-International unit
(mIU)/day), acetylleucine, or gingko biloba at least 1 month prior to first dose
(Study Day 0).

10. Agree to discontinue any other investigational treatments for NPC including vorinostat
or arimoclomol at least 3 months prior to first dose (Study Day 0).

11. Females of child-bearing potential (not surgically sterile) must use a medically
acceptable method of contraception and must agree to continue use of this method for
the duration of the study and for 30 days after participation in the study.

Part C:

1. Subject has completed Part B, or meets the criteria for the Rescue Option.

Key
Minimum age
4 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Exclusion criteria as assessed by NPC Clinical Severity Scale:

- Unable to walk, wheelchair dependent (ambulation NPC score=5)

- Needs a nasogastric tube to overcome swallowing difficulties (swallowing NPC
score=5) Note: Nasogastric or gastric tube use for supplemental feeding or
medication administration is permitted and will not exclude a subject from the
trial.

- Severe dysmetria (fine motor NPC score=5)

- Minimal cognitive function (cognition NPC score=5).

2. Body weight < 15 kg.

3. 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. Note: Any prior IT administration of HP-ß-CD will exclude a subject from
enrollment.

4. Subjects on antipsychotics for treatment of psychosis. Note: Use of antipsychotic
medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity
Disorder) will not exclude a subject from this trial.

5. History of hypersensitivity reactions to any product containing
2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD).

6. Spinal deformity that could impact the ability to perform a lumbar puncture.

7. Skin infection in the lumbar region within 2 months of study entry.

8. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L.

9. Thrombocytopenia (platelet count of less than 75 X 10^9/L).

10. 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. Status epilepticus occurring within 3 months of screening and/or seizure frequency
that cannot be quantified.

12. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.

13. Recent use of anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re:
lumbar puncture safety].

14. Subjects unable to comply with the study procedures or with 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/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 Part A and B, two out of every three patients will receive the study drug. The doctor will
give the third patient an injection with nothing in it (sham control).

In Part C, all participants will receive study drug.
Trial website
https://clinicaltrials.gov/show/NCT02534844
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Team Leader
Address 0 0
Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company
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
Other publications