This study evaluates the efficacy and safety of 2-hydroxypropyl-β-cyclodextrin (VTS-270) in patients with neurologic manifestations of Niemann-Pick Type C1 (NPC1) Disease. Approximately two-thirds of patients will receive the study drug, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), while the remaining study participants will receive sham control.



Eligible Ages
Between 4 Years and 21 Years
Eligible Genders
Accepts Healthy Volunteers

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 2/Phase 3
Study Type
Intervention Model
Parallel Assignment
Primary Purpose
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Part A: Three (3) different VTS-270 lumbar intrathecal doses (900 mg, 1200 mg, and 1800 mg) administered IT every 2 weeks for 8 weeks in 9 subjects; 3 subjects will receive sham treatment. Dose for Part B to be selected for the remainder of the study. Part B: Approximately 51 subjects, including 12 from Part A, will receive lumbar intrathecal infusions of VTS-270 or sham (randomized 2:1) every 2 weeks for a total of 52 weeks. Part C: Open-label extension with IT treatment every 2 weeks. All subjects (sham and drug-treated) with clinically defined worsening following > 6 months of treatment in Part B will be eligible to enter Part C. All subjects who complete Part B will be eligible to enter Part C.
  • Drug: VTS-270
    Lumber intrathecal infusion of VTS-270 (dose to be selected after Part A)
    Other names:
    • 2-hydroxypropyl-β-cyclodextrin
    • Cyclodextrin
Sham Comparator
Sham Procedure Control
Sixteen (16) subjects, including 3 from Part A.
  • Drug: Sham Procedure Control
    No experimental drug administered to patients. All intrathecal administrations are simulated.
    Other names:
    • Sham group

More Details

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

Study Contact

Detailed Description

Non-clinical studies and a Phase 1 clinical trial suggest that intrathecal administration of 2-hydroxypropyl- β-cyclodextrin (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 is a multicenter, multinational, prospective, randomized, double-blind, sham-controlled, 3-part, efficacy and safety trial of VTS-270, administered by the lumbar intrathecal route (IT) every 2 weeks, with a planned enrollment of approximately 51 subjects with NPC1 disease. The study will be conducted in three parts: Parts A, B, and C.

Part A will evaluate 3 different dose levels of VTS-270 in 9 subjects and 3 sham control subjects to determine the dose level for Parts B and C.

Part B will evaluate the safety and efficacy of the dose selected from Part A compared to sham control in 51 subjects, including the 12 subjects from Part A.

Part C will be an open-label extension phase of the study to subjects who either complete Part B or are subjects in Part B who have met rescue therapy criteria.

Subjects in Part C will receive treatment with VTS-270 until the product is licensed or the program is terminated.


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.