Purpose

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.

Condition

Eligibility

Eligible Ages
Between 4 Years and 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

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.

Exclusion Criteria

  1. Exclusion criteria as assessed by NPC Clinical Severity Scale:
  2. Unable to walk, wheelchair dependent (ambulation NPC score=5)
  3. 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.
  4. Severe dysmetria (fine motor NPC score=5)
  5. Minimal cognitive function (cognition NPC score=5).
  6. Body weight < 15 kg.
  7. 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. Note: Any prior IT administration of HP-β-CD will exclude a subject from enrollment.
  8. 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.
  9. History of hypersensitivity reactions to any product containing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD).
  10. Spinal deformity that could impact the ability to perform a lumbar puncture.
  11. Skin infection in the lumbar region within 2 months of study entry.
  12. Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L.
  13. Thrombocytopenia (platelet count of less than 75 X 10^9/L).
  14. 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.
  15. Status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified.
  16. Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
  17. Recent use of anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
  18. 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

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
In Parts A and B interventions will be administered in parallel. All participants will become a single group for Part C,
Primary Purpose
Treatment
Masking
Double (Care Provider, Investigator)
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.

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: VTS-270
    Lumbar intrathecal infusion of VTS-270
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin
Experimental
Part A- 1200 mg VTS-270
Participants receive 1200 mg of VTS-270 administered by the lumbar IT route every 2 weeks.
  • Drug: VTS-270
    Lumbar intrathecal infusion of VTS-270
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin
Experimental
Part A- 1800 mg VTS-270
Participants receive 1800 mg of VTS-270 administered by the lumbar IT route every 2 weeks.
  • Drug: VTS-270
    Lumbar intrathecal infusion of VTS-270
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin
Other
Part A- Sham
Participants receive 1 to 2 skin pricks with a needle.
  • Other: Sham
    No experimental drug is administered to patients. All intrathecal administrations are simulated by skin prick.
    Other names:
    • Procedure Control
Experimental
Part B- 900 mg VTS-270
Participants receive 900 mg of VTS-270 administered by the lumbar IT route every 2 weeks.
  • Drug: VTS-270
    Lumbar intrathecal infusion of VTS-270
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin
Other
Part B- Sham
Participants receive 1 to 2 skin pricks with a needle.
  • Other: Sham
    No experimental drug is administered to patients. All intrathecal administrations are simulated by skin prick.
    Other names:
    • Procedure Control
Experimental
Part C- 900 mg VTS-270
Participants receive 900 mg of VTS-270 administered by the lumbar IT route every 2 weeks.
  • Drug: VTS-270
    Lumbar intrathecal infusion of VTS-270
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin

More Details

Status
Active, not recruiting
Sponsor
Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company

Study Contact

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.

Participants in Part C will receive treatment with VTS-270 until the product is licensed or the program is terminated (anticipated within 5 years).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.