Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03687476
• Date of registration: 06/08/2018
• Prospective Registration: Yes
• Primary sponsor: Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company
• Public title: Safety and Tolerability Study of VTS-270 in Pediatric Participants With Niemann-Pick Type C (NPC) Disease
• Scientific title: An Open-label, Multicenter Safety and Tolerability Study of VTS-270 (2-hydroxypropyl-ß-cyclodextrin) in Pediatric Subjects Aged < 4 Years With Neurologic Manifestations of Niemann-Pick Type C (NPC) Disease
• Date of first enrolment: May 2020
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03687476
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Contacts

• Name: Global Clinical Leader
• Affiliation: Mallinckrodt

Key inclusion & exclusion criteria

Inclusion Criteria:

1. The parent(s)/legal guardian(s) must be adequately informed and understand the nature
and risks of the study. The participant's parent or legal guardian must provide a
signature and date on the informed consent form (ICF).

2. Participants must have neurologial symptoms defined as, any area of developmental
delay 1 SD below the mean (example, developmental quotient or standard score under 85
in any domain on the Mullen Scale Early Learning [MSEL]) or a significant
developmental quotient /standard score drop on the MSEL.

3. Diagnosis of NPC determined by one of the following:

1. Two NPC1 or NPC2 mutations;

2. Positive filipin staining or oxysterol testing and at least one NPC1 or NPC2
mutation;

3. Vertical supranuclear gaze palsy in combination with either:

i. One NPC1/NPC2 mutation, or

ii. Positive filipin staining or oxysterol levels consistent with NPC1 or NPC2
disease.

4. If taking miglustat (Zavesca), participant(s) must have been on a stable dose for 6
weeks prior to the Screening Visit and willing to remain on a stable dose for the
duration of participation in this study. If not taking migulstat, the participant must
have been off treatment for a minimum of 6 weeks prior to the Baseline Visit.

5. If a participant has a history of seizures, the condition must be adequately
controlled (the pattern of seizure activity must be stable) and the participant must
be on a stable dose and regimen of antiepileptic medication(s) 4 weeks prior to the
Screening Visit.

6. Prior exposure to VTS-270 is permitted.

7. The participant's parent(s)/legal guardian(s) are able to communicate effectively with
study personnel.

8. Parent(s)/legal guardian(s) are able and willing to follow all protocol requirements
and study restrictions.

9. Parent(s)/legal guardian(s) are able and willing to return participants for all study
visits.

Exclusion Criteria:

1. Is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section
46.111(b) and other local and national regulations, including but not limited to,
employees (temporary, part-time, full time, etc) or a family member of the research
staff conducting the study, or of the sponsor, or of the contract research
organization, or of the institutional review board (IRB)/independent ethics committee
(IEC).

2. Has a history of sensitivity or allergy to any product containing HP-ß-CD.

3. A history of hypersensitivity reactions or allergy to the anesthetic and/or sedative
agents to be used for the lumbar puncture procedure.

4. Taken an anticoagulant in the 2 weeks prior to the Baseline Visit or plan to use
anticoagulants during the study.

5. Change in antiepileptic treatment between the Screening Visit and the Baseline Visit.

6. Received treatment for any investigational product (exclusive of VTS-270) within 4
weeks of the Baseline Visit or at least 5 half-lives, whichever criteria is longest.

7. A suspected infection of the central nervous system or any systemic infection.

8. A spinal deformity that is likely to impact the ability to perform repeated LPs.

9. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.

10. Undergoing intravenous treatment with VTS-270. Note: prior or current treatment with
IT VTS-270 is not exclusionary.

11. A known bleeding disorder.

12. Has any of the following laboratory abnormalities ( greater than 1.5 times the upper
limit of normal) at the Screening Visit:

- Neutropenia

- Thrombocytopenia

- Activated partial thromboplastin time

- Prothrombin time prolongation.

13. Has any other clinically significant disease, disorder or laboratory abnormality,
which, in the opinion of the investigator, might put the participant at risk due to
participation in the study, or may influence the results of the study or the
participant's ability to complete the study.

14. Is participating in or plans to participate in any other interventional research study
from the time of screening and throughout this study.

15. Also excluded are participant, who in the opinion of the investigator, are unable to
comply with the protocol or who have a medical condition (eg, cardiovascular,
respiratory, hematologic, neurologic, psychiatric, renal) that would potentially
increase the risk of study participation.



Age minimum: N/A
Age maximum: 4 Years
Gender: All

Health Condition(s) or Problem(s) studied

Niemann-Pick Disease, Type C

Intervention(s)

Drug: VTS-270

Primary Outcome(s)

Number of Participants With Clinically Significant Vital Signs: Part A [Time Frame: Baseline up to Week 20 (End of Part A)]

Number of Participants With Clinically Significant Change from Baseline in Body Weight: Part A [Time Frame: Baseline up to Week 20 (End of Part A)]

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Part A [Time Frame: Baseline up to Week 20 (End of Part A)]

Number of Participants With Clinically Significant Laboratory Test Abnormalities: Part A [Time Frame: Baseline up to Week 20 (End of Part A)]

Number of Participants With Clinically Significant Change from Baseline in Body Height: Part A [Time Frame: Baseline up to Week 20 (End of Part A)]

Secondary Outcome(s)

Change From Baseline in Auditory Brainstem Response (ABR) Assessed Using Standard Clinical Pediatric Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years) [Time Frame: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)]

Number of Participants With Clinically Significant Vital Signs: Part B [Time Frame: Week 22 up to 3 years (End of Study or Part B)]

Change From Baseline in Caregiver Global Impression of Change (CGIC) Using Likert Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years) [Time Frame: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)]

Change From Baseline in Audiological Examinations at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years) [Time Frame: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)]

Change From Baseline in Cognitive and Motor Development Assessed Using Mullen Scale of Early Learning (MSEL) at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years) [Time Frame: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)]

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Part B [Time Frame: Week 22 up to 3 years (End of Study or Part B)]

Number of Participants With Clinically Significant Change from Baseline in Body Weight: Part B [Time Frame: Week 22 up to 3 years (End of Study or Part B)]

Change From Baseline in Clinician Global Impression of Change (CGIC) Using Likert Score at Week 6, 12, 20, 44, and every 24 Week Thereafter Until End of Treatment (EOT: 3 Years) [Time Frame: Baseline, Week 6, 12, 20, 44, every 24 Week thereafter until EOT (3 years)]

Number of Participants With Clinically Significant Change from Baseline in Body Height: Part B [Time Frame: Week 22 up to 3 years (End of Study or Part B)]

Number of Participants With Clinically Significant Laboratory Test Abnormalities: Part B [Time Frame: Week 22 up to 3 years (End of Study or Part B)]

Secondary ID(s)

VTS270-303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors