Niemann-Pick Disease, Type CPhase 2/3NCT02534844
VTS-270 to Treat Niemann-Pick Type C1 (NPC1) Disease
A Phase 2/3 study testing Parts A/B: Adrabetadex in people with Niemann-Pick Disease, Type C, run by Mandos LLC at 29 sites in 9 countries.
Trial summary
Due to different study designs, the sponsor separated Part C into a separate registration (NCT04958642), leaving Parts A/B here in NCT02534844. 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). Read more about this study
- Who is it for?
- Ages 4 to 21 years
- Conditions the study is for
- Niemann-Pick Disease, Type C
- What is being tested?
- Parts A/B: Adrabetadex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 29 sitesin 9 countries
- Study dates
- Oct 2015to 28 Mar 2018
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Parts A/B:
- Had onset of neurological symptoms prior to 15 years of age
- Has confirmed diagnosis of NPC1 determined by either:
- 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 positive filipin staining or oxysterol levels consistent with NPC disease and no Niemann-Pick Type C2 (NPC2) Disease mutations
Show all 15Show fewer
- Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
- Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
- Has an NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the following components: ambulation, fine motor skills, or swallowing; and has a score of 0 through 4 on the cognition component
- Has a total NPC Clinical Severity Scale Score of 10 or greater
- If taking miglustat, must have been on a stable dose for past 6-8 weeks and be willing to remain on a stable dose
- If participant has seizures, they have been adequately controlled for 3 months without changing dose or regimen
- Has agreed to discontinue all non-prescription supplements at least 1 month prior to first dose (Study Day 0)
- Has agreed to discontinue any other investigational treatments for NPC including vorinostat or arimoclomol at least 3 months prior to first dose (Study Day 0)
- If of child-bearing potential (not surgically sterile), agrees to use a medically acceptable method continuously, until at least 30 days after participation in the study
Who cannot join
- Has exclusion criteria as assessed by NPC Clinical Severity Scale:
- Unable to walk, wheelchair dependent (ambulation NPC score=5)
- Has need for a nasogastric tube to overcome swallowing difficulties (swallowing NPC score=5) unless used for supplemental feeding or administering medication
- severe dysmetria (fine motor score =5) or
- minimal cognitive function (cognition NPC score=5)
- Weighs less than 15 kg
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- Has had 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, or has had any prior intrathecal (IT) administration of HP-β-CD
- Is taking antipsychotics for treatment of psychosis; use of antipsychotic medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity Disorder) will not exclude participation in this trial
- Has a history of hypersensitivity reactions to any product containing HP-β-CD
- Has a spinal deformity that could impact the ability to perform a lumbar puncture
- Has had a skin infection in the lumbar region within 2 months of study entry
- Has neutropenia, defined as an absolute neutrophil count (ANC) of less than 1.5 X 10^9/L
- Has thrombocytopenia (platelet count of less than 75 X 10^9/L)
- Has 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
- Has had status epilepticus occurring within 3 months of screening and/or seizure frequency that cannot be quantified
- Has evidence of either obstructive hydrocephalus or normal pressure hydrocephalus
- Has recently used anticoagulants [in past 2 weeks prior to first dose (Study Day 0); re: lumbar puncture safety].
- Is unable to comply with the study procedures or has a clinical disease or laboratory abnormality that in the opinion of the investigator would potentially increase the risk of participation
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
United States14 sites
Lehigh Valley Health Network
Allentown, Pennsylvania, 18101
University of Colorado Denver
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Bethesda, Maryland, 20892-2425
University of Alabama at Birmingham
Birmingham, Alabama, 35223
Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina
Chapel Hill, North Carolina, 27514
Rush University Medical Center
Chicago, Illinois, 60612
Shands Children's Hospital
Gainesville, Florida, 32608
Children's Hospital of Orange County
Orange, California, 92867
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of California San Francisco
San Francisco, California, 94143-0780
Multicare Institute for Research and Innovation
Tacoma, Washington, 98405
Montefiore Medical Center
The Bronx, New York, 10467
Australia4 sites
Monash Medical Centre
Clayton, Victoria, 3168
Royal Melbourne Hospital
Parkville, Victoria, 3050
Royal Perth Hospital
Perth, Western Australia, 6000
The Prince of Wales Hospital
Sydney, New South Wales, 2031
Germany3 sites
Katholisches Klinikim Bochum gGmbH
Bochum, 44791
Universitaetsklinikum Mainz
Mainz, 55131
Universitaetsklinikum Muenster
Münster, 48149
Turkey (Türkiye)2 sites
Hacettepe University Medical Faculty
Altındağ, Ankara, 06230
Gazi University Medical Faculty
Çankaya, Ankara, 06570
United Kingdom2 sites
Birmingham Women's and Children's NHS Trust
Birmingham, West Midlands, B4 6NH
Great Ormond Street Hospital
London, WC1N 3JH
France1 site
CHU Paris Est - Hospital d'Enfants Armand-Trousseau
Paris, Cedex 12, 75 571
Singapore1 site
National University Hospital (Singapore) Pte, Ltd
Singapore, 119074
About this study
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
Due to different study designs, the sponsor separated Part C into a separate registration (NCT04958642), leaving Parts A/B here in NCT02534844.
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).
Read more
In Parts A/B, two out of every three patients will receive the study drug. The third patient will receive 1 to 2 small needle pricks at the location where the LP and IT injection is normally made (sham control).
In Part C, all participants will receive study drug, as described in the Part C registration record.
Start date for this record is the first day a participant was enrolled in Parts A/B. The trial is actually continuing until the last primary outcome measure of safety data are collected from Part C participants. The last primary outcome measure of safety, along with final adverse events results will be posted in the separate Part C registration record.
Read the 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, as well as participants entering Part C from other trials.
Participants in Part C will receive treatment with VTS-270 until the product is licensed or the program is terminated (anticipated within 5 years).
Final results will be posted in the Part C registration record (NCT04958642).
- Conditions
- Niemann-Pick Disease, Type C
- Being tested
- Parts A/B: Adrabetadex, Parts A/B: Sham Control
- Keywords
- Niemann-Pick Type C1 (NPC1) Disease, neurologic disease, gross motor dysfunction, fine motor dysfunction, dysphagia, swallowing problems, cognitive dysfunction, gait abnormalities, pediatrics
- Medical subject headings
- Niemann-Pick Disease, Type C, Disease, Deglutition Disorders, Cognitive Dysfunction, Mobility Limitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parts A/B: AdrabetadexDrug
Also called 2-hydroxypropyl-β-cyclodextrin, Cyclodextrin, VTS-270, Adrabetadex
900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion
Parts A/B: Sham ControlOther
Also called Procedure Control, Skin prick
No experimental drug is administered to participants - intrathecal administrations are simulated by skin prick
| Study group | Role | What they receive |
|---|---|---|
| Parts A/B: Sham Control | Experimental | Participants receive no study drug Receives: Other: Parts A/B: Sham Control |
| Parts A/B: Adrabetadex | Other | Participants receive adrabetadex Receives: Drug: Parts A/B: Adrabetadex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score
The NPC-SS composite score is the sum of the ambulation, cognition, fine motor, and swallowing domains of the NPC-SS. Each of the four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The total score was the sum of individual components scores which ranges from 0 (best) to 20 (worst), with higher scores indicating more severe clinical impairment.
Measured: Baseline, Week 52
Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52
The Clinician CGIC is a 7-point Likert scale. The scale requires assessment of change from a baseline level of disease activity, with anchors ranging from markedly improved, moderately improved, and minimally improved to no change and corresponding worsening (minimally, moderately, markedly). The Investigator rates his/her impression of the change in each participant's condition at week 52 on a scale from marked improvement (1) to marked worsening (7).
Measured: Week 52
Secondary outcomes (12)
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and auditory brainstem response modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual component scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment.
Measured: Baseline, Week 52
Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52
The Clinician CGIC is a 7-point Likert scale. The scale requires assessment of change from a baseline level of disease activity, with anchors ranging from markedly improved, moderately improved, and minimally improved to no change and corresponding worsening (minimally, moderately, markedly). The Investigator rates his/her impression of the change in each participant's condition at week 52 on a scale from marked improvement (1) to marked worsening (7). CGIC Responders are defined as participants who received the caregiver's rating of no change, minimally improved, moderately improved, or markedly improved from baseline to Week 52.
Measured: Week 52
Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. The hearing domain and ABR modifiers are removed from the total NPC-SS total score for this measure. A Likert-like scale is used to assign the remaining 8 major domain scores of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 40 (worst), with higher scores indicating more severe clinical impairment. Responders on NPC-SS Total Score are defined as participants with no change or improvement on NPC-SS total score from baseline to Week 52.
Measured: Week 52
Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
The EQ-5D-3L assessment is a self-reported, simple, descriptive system measuring 5 dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranges from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
Measured: Baseline, Week 52
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Participants who manifested significant disease progression according to predefined clinical criteria after treatment of 26 weeks or more had the option to rescue. Number of participants who qualified for the rescue option following a minimum of 26 weeks of treatment were analyzed.
Measured: Baseline up to Week 26
Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse) with higher scores indicating more severe clinical impairment.
Measured: Baseline, Week 52
Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
The NPC-SS total score is based on 9 domains including ambulation, fine motor skills, cognition, swallowing, memory, speech, eye movement, hearing (sensorineural) and seizures. A Likert-like scale is used to assign to each domain score of 0 to 5 (better to worse). The total score was the sum of individual components scores which ranges from 0 (best) to 45 (worst), with higher scores indicating more severe clinical impairment.
Measured: Baseline, Week 52
Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite Score
The NPC-SS composite score is the sum of the ambulation, cognition, fine motor, and swallowing domains of the NPC-SS. Each of the four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The total score was the sum of individual components scores which ranges from 0 (best) to 20 (worst), with higher scores indicating more severe clinical impairment. The product-limit survival analysis method is used to estimate the time to one point increase (worsening) in NPC-SS composite score. Time to worsening in NPC-SS Composite Score defined as the interval from study drug administration to a one point increase in the NPC-SS composite score. If a subject discontinued from the study prior to Week 52, then the subject was censored at time of discontinuation. If a subject completed the Week 52 visit, then the subject was censored at the time of last study visit.
Measured: Baseline up to Week 52
Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
The TUG is a test of balance and risk for falls. This test measures the time taken by a participant to walk 3 meters starting from a sitting position and it ends when the participant is seated again.
Measured: Baseline, Week 52
Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
The 9-Hole Peg Test is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded.
Measured: Baseline, Week 52
Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event (AE) with onset on or after start of study Drug. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Baseline up to Week 52
Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite Score
The NPC-SS composite score is the sum of the ambulation, cognition, fine motor, and swallowing domains of the NPC-SS. Each of the four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The total score was the sum of individual components scores which ranges from 0 (best) to 20 (worst), with higher scores indicating more severe clinical impairment. The Annualized rate of change (Slope) is calculated as 365.25 *([measurement at post-baseline visit - measurement at baseline]/[date of post-baseline visit - date of baseline visit + 1]).
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2015 (estimated)
- Study startOct 2015
- Primary completion28 Mar 2018
- Study completion28 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Niemann-Pick Disease, Type CStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In Parts A/B (see other registration for Part C description)
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mandos LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Lead, Study director, Mandos LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02534844
- Sponsor's protocol ID
- VTS301 (Parts A/B)
- Other IDs
- 2015-002548-15, 2015
- Status last verified
- Feb 2023
- First submitted
- 18 Aug 2015
- Last updated
- 22 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT02534844) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.
Publications
Farmer 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 40525490
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02534844
- Acronym / sponsor ID
- VTS301 (Parts A/B)
- Conditions
- Niemann-Pick Disease, Type C
- Keywords
- Niemann-Pick Type C1 (NPC1) Disease, neurologic disease, gross motor dysfunction, fine motor dysfunction, dysphagia, swallowing problems, cognitive dysfunction, gait abnormalities
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Mandos LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2015 (actual)
- Primary completion
- 28 Mar 2018 (actual)
- Study completion
- 28 Mar 2018 (actual)
- First posted
- 28 Aug 2015 (estimated)
- Results
- Posted 22 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Due to different study designs, the sponsor separated Part C into a separate registration (NCT04958642), leaving Parts A/B here in NCT02534844.
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 Parts A/B, two out of every three patients will receive the study drug. The third patient will receive 1 to 2 small needle pricks at the location where the LP and IT injection is normally made (sham control).
In Part C, all participants will receive study drug, as described in the Part C registration record.
Start date for this record is the first day a participant was enrolled in Parts A/B. The trial is actually continuing until the last primary outcome measure of safety data are collected from Part C participants. The last primary outcome measure of safety, along with final adverse events results will be posted in the separate Part C registration record.
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, as well as participants entering Part C from other trials.
Participants in Part C will receive treatment with VTS-270 until the product is licensed or the program is terminated (anticipated within 5 years).
Final results will be posted in the Part C registration record (NCT04958642).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
- Model description
- In Parts A/B (see other registration for Part C description)
| Arm | Type | Receives |
|---|---|---|
| Parts A/B: Sham Control | Experimental | Other: Parts A/B: Sham ControlParticipants receive no study drug |
| Parts A/B: Adrabetadex | Other | Drug: Parts A/B: AdrabetadexParticipants receive adrabetadex |
Who may qualify
- Ages
- 4 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Had onset of neurological symptoms prior to 15 years of age
- Has confirmed diagnosis of NPC1 determined by either:
- Adult participant or parent/guardian has provided written informed consent, with assent collected from minors of appropriate age
- Is able to undergo a lumbar puncture (LP) and IT drug administration under conscious sedation or general anesthesia
- Has an NPC Clinical Severity Scale Score of 1 through 4, inclusive, in two or more of the following components: ambulation, fine motor skills, or swallowing; and has a score of 0 through 4 on the cognition component
Key exclusion criteria (18 listed)
- Has exclusion criteria as assessed by NPC Clinical Severity Scale:
- Weighs less than 15 kg
- Has had 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, or has had any prior intrathecal (IT) administration of HP-β-CD
- Is taking antipsychotics for treatment of psychosis; use of antipsychotic medication for treatment of other disorders (e.g., Attention Deficit Hyperactivity Disorder) will not exclude participation in this trial
- Has a history of hypersensitivity reactions to any product containing HP-β-CD
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 |
|---|---|---|
| Parts A/B: AdrabetadexAlso: 2-hydroxypropyl-β-cyclodextrin, Cyclodextrin, VTS-270, Adrabetadex900 - 1800 milligram (mg) of adrabetadex administered every 2 weeks via lumbar intrathecal infusion | Drug | Parts A/B: Adrabetadex |
| Parts A/B: Sham ControlAlso: Procedure Control, Skin prickNo experimental drug is administered to participants - intrathecal administrations are simulated by skin prick | Other | Parts A/B: Sham Control |
Primary outcome
Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score
Time frame: Baseline, Week 52
The NPC-SS composite score is the sum of the ambulation, cognition, fine motor, and swallowing domains of the NPC-SS. Each of the four NPC-SS components (ambulation, cognition, fine motor, and swallowing) are rated on a scale from 0 (better) to 5 (worse). The total score was the sum of individual components scores which ranges from 0 (best) to 20 (worst), with higher scores indicating more severe clinical impairment.
Parts A/B: Number of Participants Classified With Each Score on the Clinician Global Impression of Change (CGIC) at Week 52
Time frame: Week 52
The Clinician CGIC is a 7-point Likert scale. The scale requires assessment of change from a baseline level of disease activity, with anchors ranging from markedly improved, moderately improved, and minimally improved to no change and corresponding worsening (minimally, moderately, markedly). The Investigator rates his/her impression of the change in each participant's condition at week 52 on a scale from marked improvement (1) to marked worsening (7).
12 secondary outcomes
Parts A/B: Change From Baseline to Week 52 in NPC-SS Total Score (Excluding Hearing and Auditory Brainstem Response [ABR])
Time frame: Baseline, Week 52
Parts A/ B: Number of Participants Classified as CGIC Responders at Week 52
Time frame: Week 52
Parts A/B: Number of Participants Classified as Responders on NPC-SS Total Score (Excluding Hearing and ABR) at Week 52
Time frame: Week 52
Parts A/B: EQ-5D-3L Questionnaire Visual Analog Scale (VAS) Score (for Health Status) at Baseline and at Week 52
Time frame: Baseline, Week 52
Parts A/B: Number of Participants Treated for at Least 6 Months Who Qualified for the Rescue Option
Time frame: Baseline up to Week 26
Parts A/B: Change From Baseline to Week 52 in Each of the 9 Clinical Domains of the NPC-SS
Time frame: Baseline, Week 52
Parts A/B: Change From Baseline to Week 52 in the Total NPC-SS (With Hearing Domain and ABR Modifier Included)
Time frame: Baseline, Week 52
Parts A/B: Time to One Point Increase (Worsening) in NPC-SS Composite Score
Time frame: Baseline up to Week 52
Parts A/B: Change From Baseline in the Timed Up and Go (TUG) Test at Week 52
Time frame: Baseline, Week 52
Parts A/B: Change From Baseline in the 9-Hole Peg Test at Week 52
Time frame: Baseline, Week 52
Parts A/B: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline up to Week 52
Parts A/B: Change From Baseline to Week 52 in Mean Annualized Rate of Change (Slope) of NPC-SS Composite Score
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
- Individual participant dataSharing planned: No. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT02534844) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.
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RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease (NPC)
Niemann-Pick Type C Disease
RecruitingPhase 3
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease, GM1 Gangliosidosis or GM2 Gangliosidosis
Niemann-Pick Type C Disease, GM1 Gangliosidosis
RecruitingObservational study
Evaluation of Biochemical Markers and Clinical Investigation of Niemann-Pick Disease, Type C
Niemann-Pick Disease, Type C
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.
Clinical Study Lead study director
Mandos LLC
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Parts A/B: Adrabetadex in people with Niemann-Pick Disease, Type C, run by Mandos LLC at 29 sites in 9 countries.
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 15 inclusion and 18 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 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, Germany, Turkey (Türkiye), United Kingdom and 4 more countries. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Parts A/B: Change From Baseline to Week 52 in 4-Item Composite Score of Niemann Pick Type C Severity Scale (NPC-SS) Score (time frame: Baseline, Week 52). The study lists 2 primary outcomes in all. 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 NCT02534844, which also lists 1 linked publication.
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 22 Feb 2023.