Niemann-Pick Disease, Type C1Phase 1NCT01747135
Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease
A Phase 1 study testing VTS-270 in people with Niemann-Pick Disease, Type C1, run by Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company at 1 site in United States.
Trial summary
Background: Hydroxypropyl beta cyclodextrin (HPBCD) is being tested for a disease called Niemann-Pick disease type C1 (NPC1). NPC1 is a genetic disorder that results in gradual loss of nervous system function. Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Niemann-Pick Disease, Type C1
- What is being tested?
- VTS-270
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Aged greater than or equal to 2 and less than or equal to 25 years old at time of enrollment, either gender and any ethnicity.
- Diagnosis of NPC1 based upon one of the following:
- Two NPC1 mutations;
- Positive filipin staining and at least one NPC1 mutation;
- Vertical supranuclear gaze palsy (VSNGP) in combination with either:
- One NPC1 mutation, or
Show all 13Show fewer
- Positive filipin staining and no Niemann-Pick Type 2 (NPC2) mutations.
- Patients with at least one neurological manifestation of NPC1. For example, but not limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia, dystonia, seizures, dysarthria, or dysphagia.
- Ability to travel to the National Institutes of Health Clinical Center (NIH CC) repeatedly for evaluation and follow-up.
- If taking miglustat, the patient must have been taking a constant dose of the medication for no less than 3 months prior to baseline evaluation and must be willing to maintain that dose level for the duration of the trial.
- Willing to discontinue all non-prescription supplements, with the exception of an age-appropriate multivitamin.
- Women of reproductive age must be willing to use an effective method of contraception for the duration of the trial.
- Willing to participate in all aspects of trial design including serial blood and cerebrospinal fluid (CSF) collections.
Who cannot join
- <!-- -->
- Aged below 2 or above 25 years of age at enrollment in the trial.
- Subjects will be excluded if their weight would result in an endotoxin level that would exceed 0.2 EU/kg for either the saline or drug dosing.
- Severe manifestations of NPC1 that would interfere with the patient's ability to comply with the requirements of this protocol.
- Neurologically asymptomatic patients.
- Patients who have received any form of cyclodextrin in an attempt to treat NPC1. Treatment with another drug preparation for another medical indication that contains cyclodextrin as an excipient, will not exclude a patient.
Show all 26Show fewer
- History of hypersensitivity reactions to cyclodextrin or components of the formulation.
- Pregnancy or breastfeeding at any time during the study.
- Patients with suspected infection of the CNS or any systemic infection.
- Spinal deformity that would impact the ability to perform a lumbar puncture
- Skin infection in the lumbar region
- Neutropenia, defined as an absolute neutrophil count (ANC) of less than 1,500.
- Thrombocytopenia (a platelet count of less than 75,000 per cubic millimeter).
- Evidence of disturbed circulation of CSF.
- Contraindication for anesthesia.
- Prior use of anticoagulants or history/presence of a bleeding disorder with increased risk of clinical bleeding or an international normalized ratio (INR) greater than 2.
- Patients with clinical evidence of acute liver disease having symptoms of jaundice or right upper quadrant pain.
- Presence of anemia defined as two standard deviations below normal for age and gender.
- For subjects 18 years of age and older, the epidermal growth factor receptor (eGFR) is automatically calculated and reported by the NIH CC laboratory utilizing the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine 2009 equation. We will exclude subjects greater than or equal to 18 years of age if eGFR is less than or equal to 60 mL/min/1.73 m2. For subjects < 18
- 12 years of age, we will utilize the national kidney disease education program (NKDEP) calculator (http://www.nkdep.nih.gov/lab-evaluation/gfr-calculators/children-conventional-unit.shtml). Results are reported as > 75 mL/min/1.73 m2 or lower. We will exclude subjects < 18 years of age if eGFR is less than or equal to 75 15 mL/min/1.73 m2
- 19. Hematuria on a single urinalysis, as defined by the American Urological Association (AUA) as five or more red blood cells per high-power field (or > 25/micro L) on microscopic evaluation of urinary sediment from a properly collected urinalysis specimen. The patient will not be excluded if 2 subsequent urine specimens are negative for hematuria as defined by the AUA.
- 20. Proteinuria (1+ protein on urinalysis) unless evaluated and classified as benign by patient s primary medical provider or by NIH nephrology consult or in the context of normal urine protein creatinine ratio and in the absence of clinical symptoms (edema, hypertension).
- 21. Active pulmonary disease, oxygen requirement or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
- 22. Patients unable to complete a behavioral audiologic evaluation including pure-tone threshold assessment (500 Hz to 8000 Hz) to monitor for ototoxicity and for whom otoacoustic emissions (OAEs) cannot be reliably obtained at baseline.
- 23. Patients with ongoing seizures, that are not stable in frequency, type or duration over a 2 month period prior to enrollment, requiring change in dose of antiepileptic medication (other than adjustment for weight) over a 2 month period prior to enrollment, or requiring 3 or more antiepileptic medications to control seizures.
- 24. Patients, who in the opinion of the investigators are unable to comply with the protocol or have specific health concerns that would potentially increase the risk of participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Hydroxypropyl beta cyclodextrin (HPBCD) is being tested for a disease called Niemann-Pick disease type C1 (NPC1). NPC1 is a genetic disorder that results in gradual loss of nervous system function. Cholesterol and other fats have trouble moving out of the brain cells, which makes the cells work poorly and leads to symptoms. There is no treatment currently approved in the US for NPC1. Researchers want to test if it is safe to use HPBCD for NPC1. They want to see if it can help brain cells process cholesterol better.
Read more
Objectives:
- To test the safety and effectiveness of HPBCD for NPC1.
Eligibility:
- Individuals between 2 and 25 years of age who have been diagnosed with NPC1 and who have not already received HPBCD in an attempt to treat NPC1.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples for screening. They will also have neurological tests, including tests of hearing, speech and movement.
- Participants will have a lumbar puncture (also called a spinal tap) every month to deliver the drug to the spinal fluid that surrounds the brain. The length of the trial will be determined by the safety and efficacy information that is obtained.
- Treatment will be monitored with frequent blood and urine tests, cerebral spinal fluid tests, hearing and neurological exams.
Read the detailed description
Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). The National Institutes of Health (NIH) Therapeutics for Rare and Neglected Diseases (TRND) program is developing 2-hydroxypropyl-Beta-cyclodextrin (HP-Beta-CD) for the treatment of patients with Niemann-Pick disease type C1 (NPC1) to slow progression of symptoms of the disease. In this Phase 1, non-randomized, open-label, single-center, study, we propose to administer HP-Beta-CD intrathecally via lumbar injection to drug naive cohorts of 3 patients at doses of 200 mg escalated to 300, 400 mg and 900 mg. Subsequent dose escalations may occur in increments of up to 300 mg. The objectives of this study are to assess the safety, tolerability, feasibility, and pharmacokinetics (PK) of intrathecally (IT) administered HP-Beta-CD to NPC1 patients, to determine an active dose of HP-Beta-CD as measured by changes in plasma 24-(S) hydroxycholesterol (24(S)-HC) concentration, and to evaluate the use of biomarkers and potential clinical outcomes of NPC1. All patients in the cohort will receive HP-Beta-CD (n = 3) once monthly for at least two doses, and the decision to dose-escalate will be based on safety and on biochemical data. Safety will be assessed by adverse events (AEs), audiologic evaluation, clinical laboratory tests, vital signs, physical examinations, chest X-rays and electrocardiograms (ECGs). Biochemical efficacy will be measured by change from baseline in plasma 24(S)-HC. PK will be assessed for plasma HP-Beta-CD.
- Conditions
- Niemann-Pick Disease, Type C1
- Being tested
- VTS-270
- Keywords
- 2-Hydroxypropyl-B-Cyclodextrin, Niemann-Pick Disease, Type C1, Neurodegeneration
- Medical subject headings
- Niemann-Pick Disease, Type C, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VTS-270Drug
Also called 2-hydroxypropyl-beta-cyclodextrin
| Study group | Role | What they receive |
|---|---|---|
| Open label | Experimental | Not described Receives: Drug: VTS-270 |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hydroxycholesterol Area under the curve
Measured: Days
Secondary outcomes (1)
Hearing loss.
Measured: Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Niemann-Pick Disease, Type C1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Mallinckrodt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01747135
- Sponsor's protocol ID
- 130001
- Status last verified
- Jul 2021
- First submitted
- 8 Dec 2012
- Last updated
- 23 Jul 2021
- Results posted
- No
- Individual data sharing
- No: Publish in peer reviewed journal
Publications
Aqul A, Liu B, Ramirez CM, Pieper AA, Estill SJ, Burns DK, Liu B, Repa JJ, Turley SD, Dietschy JM. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci. 2011 Jun 22;31(25):9404-13. doi: 10.1523/JNEUROSCI.1317-11.2011.
PubMed 21697390Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007 Jul 30;59(7):645-66. doi: 10.1016/j.addr.2007.05.012. Epub 2007 May 29.
PubMed 17601630Chen FW, Li C, Ioannou YA. Cyclodextrin induces calcium-dependent lysosomal exocytosis. PLoS One. 2010 Nov 29;5(11):e15054. doi: 10.1371/journal.pone.0015054.
PubMed 21124786Farmer C, Lewis M, Farhat N, Robbins KP, Joseph L, Albert OK, Bianconi S, Hoffmann A, Giserman-Kiss I, Alexander DM, Thurm A, Porter FD, Kravis EB. Convergent Validity of the Fine Motor, Speech, and Cognitive Domains of the 5-Domain Niemann-Pick Disease Type C Clinical Severity Scale. J Child Neurol. 2026 Jan;41(1):43-53. doi: 10.1177/08830738251346348. Epub 2025 Jun 17.
PubMed 40525490Boenzi S, Catesini G, Sacchetti E, Tagliaferri F, Dionisi-Vici C, Deodato F. Comprehensive-targeted lipidomic analysis in Niemann-Pick C disease. Mol Genet Metab. 2021 Dec;134(4):337-343. doi: 10.1016/j.ymgme.2021.11.005. Epub 2021 Nov 16.
PubMed 34810067Farmer CA, Thurm A, Farhat N, Bianconi S, Keener LA, Porter FD. Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-beta-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1. CNS Drugs. 2019 Jul;33(7):677-683. doi: 10.1007/s40263-019-00642-2.
PubMed 31187454
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease
- ClinicalTrials.gov ID
- NCT01747135
- Acronym / sponsor ID
- 130001
- Conditions
- Niemann-Pick Disease, Type C1
- Keywords
- 2-Hydroxypropyl-B-Cyclodextrin, Niemann-Pick Disease, Type C1, Neurodegeneration
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vtesse, LLC, a Mallinckrodt Pharmaceuticals CompanyIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 11 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Hydroxypropyl beta cyclodextrin (HPBCD) is being tested for a disease called Niemann-Pick disease type C1 (NPC1). NPC1 is a genetic disorder that results in gradual loss of nervous system function. Cholesterol and other fats have trouble moving out of the brain cells, which makes the cells work poorly and leads to symptoms. There is no treatment currently approved in the US for NPC1. Researchers want to test if it is safe to use HPBCD for NPC1. They want to see if it can help brain cells process cholesterol better.
Objectives:
- To test the safety and effectiveness of HPBCD for NPC1.
Eligibility:
- Individuals between 2 and 25 years of age who have been diagnosed with NPC1 and who have not already received HPBCD in an attempt to treat NPC1.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples for screening. They will also have neurological tests, including tests of hearing, speech and movement.
- Participants will have a lumbar puncture (also called a spinal tap) every month to deliver the drug to the spinal fluid that surrounds the brain. The length of the trial will be determined by the safety and efficacy information that is obtained.
- Treatment will be monitored with frequent blood and urine tests, cerebral spinal fluid tests, hearing and neurological exams.
Detailed description
Niemann-Pick disease type C (NPC) is a lethal, autosomal recessive, lysosomal storage disorder characterized by neurodegeneration in early childhood and death in adolescence. The causative genes NPC1 (about 95% of cases) and NPC2 (about 5% of cases) are involved in the intracellular trafficking of lipids and cholesterol. Mutations on either of these genes lead to progressive accumulation of unesterified cholesterol and other lipids in the central nervous system (CNS). The National Institutes of Health (NIH) Therapeutics for Rare and Neglected Diseases (TRND) program is developing 2-hydroxypropyl-Beta-cyclodextrin (HP-Beta-CD) for the treatment of patients with Niemann-Pick disease type C1 (NPC1) to slow progression of symptoms of the disease. In this Phase 1, non-randomized, open-label, single-center, study, we propose to administer HP-Beta-CD intrathecally via lumbar injection to drug naive cohorts of 3 patients at doses of 200 mg escalated to 300, 400 mg and 900 mg. Subsequent dose escalations may occur in increments of up to 300 mg. The objectives of this study are to assess the safety, tolerability, feasibility, and pharmacokinetics (PK) of intrathecally (IT) administered HP-Beta-CD to NPC1 patients, to determine an active dose of HP-Beta-CD as measured by changes in plasma 24-(S) hydroxycholesterol (24(S)-HC) concentration, and to evaluate the use of biomarkers and potential clinical outcomes of NPC1. All patients in the cohort will receive HP-Beta-CD (n = 3) once monthly for at least two doses, and the decision to dose-escalate will be based on safety and on biochemical data. Safety will be assessed by adverse events (AEs), audiologic evaluation, clinical laboratory tests, vital signs, physical examinations, chest X-rays and electrocardiograms (ECGs). Biochemical efficacy will be measured by change from baseline in plasma 24(S)-HC. PK will be assessed for plasma HP-Beta-CD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label | Experimental | Drug: VTS-270 |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
Key exclusion criteria (26 listed)
- <!-- -->
- 12 years of age, we will utilize the national kidney disease education program (NKDEP) calculator (http://www.nkdep.nih.gov/lab-evaluation/gfr-calculators/children-conventional-unit.shtml). Results are reported as > 75 mL/min/1.73 m2 or lower. We will exclude subjects < 18 years of age if eGFR is less than or equal to 75 15 mL/min/1.73 m2
- 19. Hematuria on a single urinalysis, as defined by the American Urological Association (AUA) as five or more red blood cells per high-power field (or > 25/micro L) on microscopic evaluation of urinary sediment from a properly collected urinalysis specimen. The patient will not be excluded if 2 subsequent urine specimens are negative for hematuria as defined by the AUA.
- 20. Proteinuria (1+ protein on urinalysis) unless evaluated and classified as benign by patient s primary medical provider or by NIH nephrology consult or in the context of normal urine protein creatinine ratio and in the absence of clinical symptoms (edema, hypertension).
- 21. Active pulmonary disease, oxygen requirement or clinically significant history of decreased blood oxygen saturation, pulmonary therapy, or requiring active suction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VTS-270Also: 2-hydroxypropyl-beta-cyclodextrin | Drug | Open label |
Primary outcome
24-hydroxycholesterol Area under the curve
Time frame: Days
1 secondary outcome
Hearing loss.
Time frame: Year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
- Background: PubMed 21697390Aqul A, Liu B, Ramirez CM, Pieper AA, Estill SJ, Burns DK, Liu B, Repa JJ, Turley SD, Dietschy JM. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci. 2011 Jun 22;31(25):9404-13. doi: 10.1523/JNEUROSCI.1317-11.2011.
- Background: PubMed 17601630Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007 Jul 30;59(7):645-66. doi: 10.1016/j.addr.2007.05.012. Epub 2007 May 29.
- Background: PubMed 21124786Chen FW, Li C, Ioannou YA. Cyclodextrin induces calcium-dependent lysosomal exocytosis. PLoS One. 2010 Nov 29;5(11):e15054. doi: 10.1371/journal.pone.0015054.
- Derived from this study: PubMed 40525490Farmer C, Lewis M, Farhat N, Robbins KP, Joseph L, Albert OK, Bianconi S, Hoffmann A, Giserman-Kiss I, Alexander DM, Thurm A, Porter FD, Kravis EB. Convergent Validity of the Fine Motor, Speech, and Cognitive Domains of the 5-Domain Niemann-Pick Disease Type C Clinical Severity Scale. J Child Neurol. 2026 Jan;41(1):43-53. doi: 10.1177/08830738251346348. Epub 2025 Jun 17.
- Derived from this study: PubMed 34810067Boenzi S, Catesini G, Sacchetti E, Tagliaferri F, Dionisi-Vici C, Deodato F. Comprehensive-targeted lipidomic analysis in Niemann-Pick C disease. Mol Genet Metab. 2021 Dec;134(4):337-343. doi: 10.1016/j.ymgme.2021.11.005. Epub 2021 Nov 16.
- Derived from this study: PubMed 31187454Farmer CA, Thurm A, Farhat N, Bianconi S, Keener LA, Porter FD. Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-beta-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1. CNS Drugs. 2019 Jul;33(7):677-683. doi: 10.1007/s40263-019-00642-2.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. Publish in peer reviewed journal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Mallinckrodt
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VTS-270 in people with Niemann-Pick Disease, Type C1, run by Vtesse, LLC, a Mallinckrodt Pharmaceuticals Company at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hydroxycholesterol Area under the curve (time frame: Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01747135, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2021.