Study of VTS-270 (2-hydroxypropyl-β-cyclodextrin) to Treat Niemann-Pick Type C1 (NPC1) Disease
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ClinicalTrials.gov Identifier: NCT02534844 |
Recruitment Status :
Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : December 6, 2018
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Condition or disease | Intervention/treatment | Phase |
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Niemann-Pick Disease, Type C | Drug: VTS-270 Drug: Sham Procedure Control | Phase 2 Phase 3 |
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 51 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2b/3 Prospective, Randomized, Double-Blind, Sham-Controlled 3-Part Trial of VTS-270 (2-hydroxypropyl-β-cyclodextrin) in Subjects With Neurologic Manifestations of Niemann-Pick Type C1 (NPC1) Disease |
Actual Study Start Date : | October 2015 |
Estimated Primary Completion Date : | March 2019 |
Estimated Study Completion Date : | March 2019 |

Arm | Intervention/treatment |
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Experimental: VTS-270
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.
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Drug: VTS-270
Lumber intrathecal infusion of VTS-270 (dose to be selected after Part A)
Other Names:
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Sham Comparator: Sham Procedure Control
Sixteen (16) subjects, including 3 from Part A.
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Drug: Sham Procedure Control
No experimental drug administered to patients. All intrathecal administrations are simulated.
Other Name: Sham group |
- NPC Clinical Severity Score [ Time Frame: 52 weeks ]Data for NPC score rating will be provided to a centralized independent blinded rater who will analyze all NPC information for all subjects and assign the NPC Clinical Severity Score.
- Clinician and Caregiver Clinical Global Impression of Change [ Time Frame: 52 weeks ]The CGIC will be evaluated using a 7-point Likert scale.
- Time to get up and go test [ Time Frame: 52 weeks ]
- 9-hole peg test [ Time Frame: 52 weeks ]
- Percentage of patients with clinical worsening [ Time Frame: from week 26 through week 52 based on first dose being week 1 ]
- European Quality of Life-5 Dimensions Quality of Life Rating (EQ-5D QoL) [ Time Frame: 52 weeks ]
- Cerebrospinal fluid (CSF) biomarkers [ Time Frame: 52 weeks ]CSF will be collected from subjects receiving study drug and will be stored for possible biomarker analysis.
- Plasma protein biomarkers [ Time Frame: 52 weeks ]Plasma samples will be collected and stored for possible biomarker analysis

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Ages Eligible for Study: | 4 Years to 21 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
Parts A and B:
- Onset of neurological symptoms prior to 15 years of age.
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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.
- Subject or parent/guardian must provide written informed consent and assent (for minors).
- Ability to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia.
- 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.
- Total NPC Clinical Severity Scale Score of 10 or greater.
- If taking miglustat, must have been on a stable dose for past 3 months and be willing to remain on a stable dose.
- 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.
- 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).
- Agree to discontinue any other investigational treatments for NPC including vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0).
- 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 Exclusion Criteria:
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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).
- Body weight < 15 kg.
- 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.
- 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.
- History of hypersensitivity reactions to any product containing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD).
- Spinal deformity that could impact the ability to perform a lumbar puncture.
- Skin infection in the lumbar region within 2 months of study entry.
- Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L.
- Thrombocytopenia (platelet count of less than 75 X 10^9/L).
- 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.
- Status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified.
- Evidence of obstructive hydrocephalus or normal pressure hydrocephalus.
- Recent use of anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02534844
United States, California | |
Children's Hospital of Orange County | |
Orange, California, United States, 92868 | |
University of California San Francisco | |
San Francisco, California, United States, 94143 | |
United States, Illinois | |
Rush University Medical Center | |
Chicago, Illinois, United States, 60612 | |
United States, Maryland | |
National Institute of Child Health and Human Development at NIH | |
Bethesda, Maryland, United States, 20878 | |
United States, Massachusetts | |
Boston Children's Hospital | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Montefiore Medical Center | |
Bronx, New York, United States, 10467 | |
United States, Pennsylvania | |
Lehigh Valley Health Network | |
Allentown, Pennsylvania, United States, 18103 | |
The Children's Hospital of Philadelphia | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Texas | |
Dell Children's Medical Center of Central Texas | |
Austin, Texas, United States, 78723 | |
Australia, Victoria | |
Monash Medical Centre | |
Clayton, Victoria, Australia, 3168 | |
Royal Melbourne Hospital | |
Parkville, Victoria, Australia, 3050 | |
France | |
CHU Paris Est - Hospital d'Enfants Armand-Trousseau | |
Paris, Cadex 12, France, 75 571 | |
Germany | |
Ruhr University, St. Josefs-Hospital | |
Bochum, Germany | |
Universitätsmedizin der Johannes Gutenberg-Universität Mainz | |
Mainz, Germany | |
Spain | |
Hospital Universitario del Valle Hebron | |
Barcelona, Spain, 08035 | |
Turkey | |
Gazi Universitesi Araştırma ve Uygulama Hastanesi | |
Ankara, Turkey | |
Hacettepe Universitesi Hastanesi | |
Ankara, Turkey | |
United Kingdom | |
Birmingham Children's Hospital | |
Birmingham, United Kingdom, B4 6NH | |
Great Ormond Street Hospital | |
London, United Kingdom, WC1N 3JH |
Responsible Party: | Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company |
ClinicalTrials.gov Identifier: | NCT02534844 History of Changes |
Other Study ID Numbers: |
VTS301 |
First Posted: | August 28, 2015 Key Record Dates |
Last Update Posted: | December 6, 2018 |
Last Verified: | December 2018 |
Keywords provided by Vtesse, Inc., a Mallinckrodt Pharmaceuticals Company:
Niemann-Pick Type C1 (NPC1) Disease neurologic disease gross motor dysfunction fine motor dysfunction dysphagia |
swallowing problems cognitive dysfunction gait abnormalities pediatrics |
Additional relevant MeSH terms:
Pick Disease of the Brain Aphasia, Primary Progressive Frontotemporal Dementia Niemann-Pick Diseases Niemann-Pick Disease, Type A Niemann-Pick Disease, Type C Frontotemporal Lobar Degeneration Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Mental Disorders Aphasia Speech Disorders |
Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations Signs and Symptoms TDP-43 Proteinopathies Neurodegenerative Diseases Proteostasis Deficiencies Metabolic Diseases Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Histiocytosis, Non-Langerhans-Cell Histiocytosis |