Niemann-Pick Disease, Type C1Phase 1NCT02939547
Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)
A Phase 1 study testing Hydroxypropyl-beta-cyclodextrin in people with Niemann-Pick Disease, Type C1, run by Cyclo Therapeutics, Inc. at 2 sites in United States.
Trial summary
This research study is being conducted to find out whether Trappsol® Cyclo™, an experimental treatment for people with Niemann Pick disease Type C (NPC-1) is safe at 2 different dose levels and what effects it has on people who have this condition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Niemann-Pick Disease, Type C1
- What is being tested?
- Hydroxypropyl-beta-cyclodextrin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Oct 2017to 10 Feb 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of NPC-1 defined as one of the following
- Two NPC-1 mutations on exome gene sequencing
- One NPC-1 mutation and positive filipin staining (current or prior)
- Vertical supranuclear gaze palsy [VSGP] plus either ≥ one NPC-1 mutation or positive filipin staining and no NPC-2 mutations
- NIH NPC Severity Score <30 and with no more than 4 individual domains with a score ≥ 3.
- Age range: 18 years upwards
Show all 12Show fewer
- At least one systemic manifestation of NPC disease defined as one or more of
- Clinically detectable hepatomegaly and/or either ALT or AST outside the normal range for the study laboratory
- Clinically detectable splenomegaly
- Impaired respiratory function due to NPC or a history of pneumonia in the last 12 months
- Negative urine pregnancy test for females of child bearing potential
- Written, informed consent
Who cannot join
- The presence of NPC-2 mutations on exome gene sequencing
- Previous receipt of cyclodextrin therapy within 3 months of baseline
- Receipt of any of the following medications within 1 month of baseline: Coenzyme Q10, curcumin, cinnamon, fish oil supplements, high dose vitamin D (>500 milli-International unit (mIU)/day), acetyl leucine, or gingko biloba
- Concurrent treatment with any therapy indicated for the lowering of cholesterol such as statins, fibrates, ezetimibe
- Karnofsky score < 40
- Inability to comply with the proposed protocol assessments or any uncertainty about their ability to give meaningful, informed consent (legal guardian may give consent with patient assent)
Show all 12Show fewer
- Concurrent medical conditions representing a contraindication to any of the study medications
- Grade 3 renal impairment or worse as indicated by eGFR< 60mL/min/1.73m2
- Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or INR >1.8
- Involvement in another interventional clinical trial within the previous 6 months from baseline
- Weight <40 kg or >100 kg
- Male patients and female patients of childbearing potential who are not willing to use appropriate birth control (i.e. double barrier birth control) from enrolment until the follow-up visit
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Atlantic Health System/Morristown Medical Center
Morristown, New Jersey, 07960
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
About this study
Official title: A Phase I Study to Evaluate the Single and Multiple-dose Pharmacokinetics of Intravenous Trappsol Cyclo (HP-Beta-CD) in Patients With Niemann-Pick Disease Type C (NPC-1) and the Effects of Dosing Upon Biomarkers of NPC Disease
This research study is being conducted to find out whether Trappsol® Cyclo™, an experimental treatment for people with Niemann Pick disease Type C (NPC-1) is safe at 2 different dose levels and what effects it has on people who have this condition. NPC-1 is caused by a defect in the protein which is important for the transport of fatty substances like cholesterol out of cells. Without this protein, fats build up in the cells ultimately leading to organ damage. The way in which this experimental treatment works is not fully understood but laboratory experiments have shown that it can potentially remove cholesterol build up from the cells in people who have NPC-1. Approximately 12 patients will be asked to take part in this research study for up to 20 weeks (w) in total (including screening. treatment and follow-up). Recruitment is expected to take 6- 9 months.Patients who take part will receive treatment by an intravenous infusion every two weeks. The study will look at what the body does to the drug as well as what the drug does to the body by taking and examining blood and urine samples. A sample(s) of cerebrospinal fluid (CSF) will be taken by lumbar puncture during the first treatment dose and may be collected during subsequent doses. Liver and skin biopsy specimens will be taken to assess filipin staining. Cholesterol metabolism will be investigated in liver samples and splenic and hepatic elasticity will be assessed by ultrasound. Patients will also have their hearing tested, be asked questions by their doctor as well completing questionnaires to help assess any changes in their condition during treatment.This study is being sponsored and funded by CTD holdings Inc. It is planned to be run in the USA,.
Read the detailed description
The planned study has been designed as a Phase I, double-blind, randomised, multi-centre, parallel group study based on information and data available from the administration of Trappsol Cyclo via compassionate/named patient use in patients with NPC-1, and data on other cyclodextrin products in the scientific literature.
The study is comprised of a screening phase of up to 4w a treatment phase of 12w and a 4w follow-up. The primary objective is to compare the plasma pharmacokinetics of single and multiple doses of two different levels of IV Trappsol Cyclo. Secondary objectives include investigation of the HP-β-CD effect of different doses of IV Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism and evaluation of Trappsol concentrations in the cerebrospinal fluid (CSF) following IV administration , evaluation of the impact of treatment upon measures of neurological function including ataxia, aphasia and saccadic eye movements, and the impact of treatment upon behavioral aspects of NPC-1.
It is planned to recruit a total of 12 patients to the study. Patients will be randomised 1:1 to one of the two dose levels (1500 mg/kg or 2500 mg/kg; six patients per dose level). Treatment will be administered every two weeks by slow IV infusion over 8 to 9 hours at different concentrations to achieve the proscribed dose levels. Patients will receive treatment for a total of 12 weeks. Patients who withdraw prior to completion of the initial pharmacokinetic and pharmacodynamic assessments will be replaced.
The design of the proposed study thus enables early assessment of potential biochemical markers of response but allows for a sufficient dosing duration to enable the short-term effectiveness of Trappsol in NPC to be assessed.
The maximum dose proposed for this study is below the maximum dose for which long term clinical data is available in 2 patients (2800 mg/kg weekly for 3-5 years). Although individual clinicians have not always utilized an escalating rate of infusion, the reports of infusion related reactions in three patients suggest that this is an appropriate clinical strategy to mitigate the risk of such events and is consistent with dosing administration for other therapeutic agents. In the proposed study, treatment will be administered less frequently than has been undertaken in compassionate use. This longer dosing interval is supported by nonclinical data comparing the metabolism of cholesterol in non-human species with that in man; although a once weekly dosing interval was initially studied in man based on data in the mouse, HP-β-CD cholesterol metabolism/turnover in the mouse is 13-fold higher than in man which, in NPC, likely translates into a 13-fold slower accumulation of cholesterol in human cells compared with those of the mouse. Therefore, it is theorized that, given the slower cholesterol metabolism in humans, the dosing interval could be much less frequent in man than in mouse; however, based on what is known about cholesterol metabolism in humans and the pharmacokinetic and pharmacodynamic effect of HP-β-CD in the mouse, a dosing interval of 2 weeks in man is likely to be well within the therapeutic dosing interval and also minimizes the amount of infusions required to be administered.
- Conditions
- Niemann-Pick Disease, Type C1
- Being tested
- Hydroxypropyl-beta-cyclodextrin
- Keywords
- intravenous, cyclodextrin, compassionate, Trappsol
- Medical subject headings
- Niemann-Pick Disease, Type C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxypropyl-beta-cyclodextrinDrug
Also called Hydroxypropyl-beta-cyclodextrin (HP-β-CD)
Used in the treatment of Niemann-Pick Disease C1 ( NPC1)
| Study group | Role | What they receive |
|---|---|---|
| Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg | Active comparator | Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks Receives: Drug: Hydroxypropyl-beta-cyclodextrin |
| Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg | Active comparator | Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks Receives: Drug: Hydroxypropyl-beta-cyclodextrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Concentration ( C max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
To compare the C max of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Measured: Pre- infusion then 2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
Time to Maximum Concentration (T max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
To compare the T max of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Measured: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
Volume of Distribution of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
To compare the Volume of Distribution of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Measured: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
Elimination half-life (T1/2) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
To compare the T1/2 of Trappsol following 2 different doses.
Measured: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
Secondary outcomes (8)
CSF levels of Trappsol
To evaluate HP-β-CD concentrations in CSF following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Measured: Pre-infusion then 2,4,6,8,12 hours after the first infusion ( w1) and 8h after the start of the last infusion (W12)
Potential blood biomarkers of NPC1
To investigate the effect of 2 different doses of intravenous Trappsol upon peripheral blood biomarkers of NPC-1 disease
Measured: Screening, baseline,then at 2,4,8,12 and 14 weeks
Potential CSF biomarkers of NPC1
To investigate the effect of 2 different doses of intravenous Trappsol upon biomarkers of NPC-1 disease in CSF
Measured: Baseline, then at 12 and 14 weeks
Serum cholesterol precursors and metabolites
To investigate the effect of 2 different doses of intravenous Trappsol in patients with NPC-1 disease upon serum and lymphocytic markers of cholesterol metabolism
Measured: Screening, baseline the Days1,3,,5,8,11 and 15 after the first infusion of Trappsol then at d2,3,5,8,11and 15 after the last infusion ( W12)
Fractionated cholesterol in hepatic tissue
To investigate the effect of 2 different doses of intravenous Trappsol in patients with NPC-1 disease upon fractionated cholesterol in hepatic tissue
Measured: Baseline and 12 weeks
Splenic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores
To evaluate the effect of 2 different doses of Trappsol upon change in clinical manifestations of NPC-1 disease
Measured: Baseline then 14 weeks
Hepatic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores
To evaluate the effect of 2 different doses of Trappsol upon change in clinical manifestations of NPC-1 disease
Measured: Baseline then 14 weeks
Number of patients with treatment-related adverse events as graded by CTCAE criteria ( Version 4.03)
Events will be gathered by spontaneous reporting, clinical observation and laboratory tests including auditory tests and auditory evoked potentials to assess hearing
Measured: Screening, baseline, days 1, 2-11, weeks 2,4,6,810,12,14 and 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2016 (estimated)
- Study start11 Oct 2017
- Primary completion10 Feb 2020
- Study completion10 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cyclo Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Caroline Hastings, MD, Principal investigator, Oakland CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02939547
- Sponsor's protocol ID
- CTD-TCNPC-101
- Status last verified
- Feb 2021
- First submitted
- 21 Sep 2016
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Battisti C, Tarugi P, Dotti MT, De Stefano N, Vattimo A, Chierichetti F, Calandra S, Federico A. Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study. Mov Disord. 2003 Nov;18(11):1405-9. doi: 10.1002/mds.10541.
PubMed 14639697Coussement W, Van Cauteren H, Vandenberghe J, et al. Toxicological profile of hydroxypropyl Beta-cyclodextrin (HP-Beta-CD) in laboratory animals. In: Minutes of the Fifth International Symposium on cyclodextrins; 28-30 March 1990; Paris, France: Editions de Santé; 1990 p. 522-4.
Davidson CD, Ali NF, Micsenyi MC, Stephney G, Renault S, Dobrenis K, Ory DS, Vanier MT, Walkley SU. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS One. 2009 Sep 11;4(9):e6951. doi: 10.1371/journal.pone.0006951.
PubMed 19750228Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse. J Biol Chem. 2002 Feb 8;277(6):3801-4. doi: 10.1074/jbc.R100057200. Epub 2001 Dec 3. No abstract available.
PubMed 11733542Fischer D, Stewart AL, Bloch DA, Lorig K, Laurent D, Holman H. Capturing the patient's view of change as a clinical outcome measure. JAMA. 1999 Sep 22-29;282(12):1157-62. doi: 10.1001/jama.282.12.1157.
PubMed 10501119Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
PubMed 1202204Giese AK, Mascher H, Grittner U, Eichler S, Kramp G, Lukas J, te Vruchte D, Al Eisa N, Cortina-Borja M, Porter FD, Platt FM, Rolfs A. A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease. Orphanet J Rare Dis. 2015 Jun 17;10:78. doi: 10.1186/s13023-015-0274-1.
PubMed 26082315Gould S, Scott RC. 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): a toxicology review. Food Chem Toxicol. 2005 Oct;43(10):1451-9. doi: 10.1016/j.fct.2005.03.007. Epub 2005 Apr 19.
PubMed 16018907Greer WL, Dobson MJ, Girouard GS, Byers DM, Riddell DC, Neumann PE. Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain. Am J Hum Genet. 1999 Nov;65(5):1252-60. doi: 10.1086/302620.
PubMed 10521290Ferraioli G, Parekh P, Levitov AB, Filice C. Shear wave elastography for evaluation of liver fibrosis. J Ultrasound Med. 2014 Feb;33(2):197-203. doi: 10.7863/ultra.33.2.197.
PubMed 24449721Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163-70. doi: 10.1179/jmt.2009.17.3.163.
PubMed 20046623King KA, Gordon-Salant S, Yanjanin N, Zalewski C, Houser A, Porter FD, Brewer CC. Auditory phenotype of Niemann-Pick disease, type C1. Ear Hear. 2014 Jan-Feb;35(1):110-7. doi: 10.1097/AUD.0b013e3182a362b8.
PubMed 24225652Liu B, Li H, Repa JJ, Turley SD, Dietschy JM. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res. 2008 Mar;49(3):663-9. doi: 10.1194/jlr.M700525-JLR200. Epub 2007 Dec 12.
PubMed 18077828Liu B, Turley SD, Burns DK, Miller AM, Repa JJ, Dietschy JM. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2377-82. doi: 10.1073/pnas.0810895106. Epub 2009 Jan 26.
PubMed 19171898Mattsson N, Zetterberg H, Bianconi S, Yanjanin NM, Fu R, Mansson JE, Porter FD, Blennow K. Miglustat treatment may reduce cerebrospinal fluid levels of the axonal degeneration marker tau in niemann-pick type C. JIMD Rep. 2012;3:45-52. doi: 10.1007/8904_2011_47. Epub 2011 Sep 28.
PubMed 23430872
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Single and Multiple-dose Pharmacokinetics of Intravenous Trappsol Cyclo (HP-Beta-CD) in Patients With Niemann-Pick Disease Type C (NPC-1) and the Effects of Dosing Upon Biomarkers of NPC Disease
- ClinicalTrials.gov ID
- NCT02939547
- Acronym / sponsor ID
- CTD-TCNPC-101
- Conditions
- Niemann-Pick Disease, Type C1
- Keywords
- intravenous, cyclodextrin, compassionate, Trappsol
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Cyclo Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 10 Feb 2020 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 20 Oct 2016 (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.
This research study is being conducted to find out whether Trappsol® Cyclo™, an experimental treatment for people with Niemann Pick disease Type C (NPC-1) is safe at 2 different dose levels and what effects it has on people who have this condition. NPC-1 is caused by a defect in the protein which is important for the transport of fatty substances like cholesterol out of cells. Without this protein, fats build up in the cells ultimately leading to organ damage. The way in which this experimental treatment works is not fully understood but laboratory experiments have shown that it can potentially remove cholesterol build up from the cells in people who have NPC-1. Approximately 12 patients will be asked to take part in this research study for up to 20 weeks (w) in total (including screening. treatment and follow-up). Recruitment is expected to take 6- 9 months.Patients who take part will receive treatment by an intravenous infusion every two weeks. The study will look at what the body does to the drug as well as what the drug does to the body by taking and examining blood and urine samples. A sample(s) of cerebrospinal fluid (CSF) will be taken by lumbar puncture during the first treatment dose and may be collected during subsequent doses. Liver and skin biopsy specimens will be taken to assess filipin staining. Cholesterol metabolism will be investigated in liver samples and splenic and hepatic elasticity will be assessed by ultrasound. Patients will also have their hearing tested, be asked questions by their doctor as well completing questionnaires to help assess any changes in their condition during treatment.This study is being sponsored and funded by CTD holdings Inc. It is planned to be run in the USA,.
Detailed description
The planned study has been designed as a Phase I, double-blind, randomised, multi-centre, parallel group study based on information and data available from the administration of Trappsol Cyclo via compassionate/named patient use in patients with NPC-1, and data on other cyclodextrin products in the scientific literature.
The study is comprised of a screening phase of up to 4w a treatment phase of 12w and a 4w follow-up. The primary objective is to compare the plasma pharmacokinetics of single and multiple doses of two different levels of IV Trappsol Cyclo. Secondary objectives include investigation of the HP-β-CD effect of different doses of IV Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism and evaluation of Trappsol concentrations in the cerebrospinal fluid (CSF) following IV administration , evaluation of the impact of treatment upon measures of neurological function including ataxia, aphasia and saccadic eye movements, and the impact of treatment upon behavioral aspects of NPC-1.
It is planned to recruit a total of 12 patients to the study. Patients will be randomised 1:1 to one of the two dose levels (1500 mg/kg or 2500 mg/kg; six patients per dose level). Treatment will be administered every two weeks by slow IV infusion over 8 to 9 hours at different concentrations to achieve the proscribed dose levels. Patients will receive treatment for a total of 12 weeks. Patients who withdraw prior to completion of the initial pharmacokinetic and pharmacodynamic assessments will be replaced.
The design of the proposed study thus enables early assessment of potential biochemical markers of response but allows for a sufficient dosing duration to enable the short-term effectiveness of Trappsol in NPC to be assessed.
The maximum dose proposed for this study is below the maximum dose for which long term clinical data is available in 2 patients (2800 mg/kg weekly for 3-5 years). Although individual clinicians have not always utilized an escalating rate of infusion, the reports of infusion related reactions in three patients suggest that this is an appropriate clinical strategy to mitigate the risk of such events and is consistent with dosing administration for other therapeutic agents. In the proposed study, treatment will be administered less frequently than has been undertaken in compassionate use. This longer dosing interval is supported by nonclinical data comparing the metabolism of cholesterol in non-human species with that in man; although a once weekly dosing interval was initially studied in man based on data in the mouse, HP-β-CD cholesterol metabolism/turnover in the mouse is 13-fold higher than in man which, in NPC, likely translates into a 13-fold slower accumulation of cholesterol in human cells compared with those of the mouse. Therefore, it is theorized that, given the slower cholesterol metabolism in humans, the dosing interval could be much less frequent in man than in mouse; however, based on what is known about cholesterol metabolism in humans and the pharmacokinetic and pharmacodynamic effect of HP-β-CD in the mouse, a dosing interval of 2 weeks in man is likely to be well within the therapeutic dosing interval and also minimizes the amount of infusions required to be administered.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg | Active comparator | Drug: Hydroxypropyl-beta-cyclodextrinHydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks |
| Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg | Active comparator | Drug: Hydroxypropyl-beta-cyclodextrinHydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Confirmed diagnosis of NPC-1 defined as one of the following
- NIH NPC Severity Score <30 and with no more than 4 individual domains with a score ≥ 3.
- Age range: 18 years upwards
- At least one systemic manifestation of NPC disease defined as one or more of
- Negative urine pregnancy test for females of child bearing potential
Key exclusion criteria (12 listed)
- The presence of NPC-2 mutations on exome gene sequencing
- Previous receipt of cyclodextrin therapy within 3 months of baseline
- Receipt of any of the following medications within 1 month of baseline: Coenzyme Q10, curcumin, cinnamon, fish oil supplements, high dose vitamin D (>500 milli-International unit (mIU)/day), acetyl leucine, or gingko biloba
- Concurrent treatment with any therapy indicated for the lowering of cholesterol such as statins, fibrates, ezetimibe
- Karnofsky score < 40
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 |
|---|---|---|
| Hydroxypropyl-beta-cyclodextrinAlso: Hydroxypropyl-beta-cyclodextrin (HP-β-CD)Used in the treatment of Niemann-Pick Disease C1 ( NPC1) | Drug | Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg, Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg |
Primary outcome
Maximum Concentration ( C max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
Time frame: Pre- infusion then 2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
To compare the C max of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Time to Maximum Concentration (T max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
Time frame: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
To compare the T max of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Volume of Distribution of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
Time frame: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
To compare the Volume of Distribution of Trappsol following 2 different dose levels of intravenous Trappsol in patients with NPC-1 disease following single and multiple doses
Elimination half-life (T1/2) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels
Time frame: Pre- infusion,2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w
To compare the T1/2 of Trappsol following 2 different doses.
8 secondary outcomes
CSF levels of Trappsol
Time frame: Pre-infusion then 2,4,6,8,12 hours after the first infusion ( w1) and 8h after the start of the last infusion (W12)
Potential blood biomarkers of NPC1
Time frame: Screening, baseline,then at 2,4,8,12 and 14 weeks
Potential CSF biomarkers of NPC1
Time frame: Baseline, then at 12 and 14 weeks
Serum cholesterol precursors and metabolites
Time frame: Screening, baseline the Days1,3,,5,8,11 and 15 after the first infusion of Trappsol then at d2,3,5,8,11and 15 after the last infusion ( W12)
Fractionated cholesterol in hepatic tissue
Time frame: Baseline and 12 weeks
Splenic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores
Time frame: Baseline then 14 weeks
Hepatic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores
Time frame: Baseline then 14 weeks
Number of patients with treatment-related adverse events as graded by CTCAE criteria ( Version 4.03)
Time frame: Screening, baseline, days 1, 2-11, weeks 2,4,6,810,12,14 and 18
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 21 Feb 2021.
- Background: PubMed 14639697Battisti C, Tarugi P, Dotti MT, De Stefano N, Vattimo A, Chierichetti F, Calandra S, Federico A. Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study. Mov Disord. 2003 Nov;18(11):1405-9. doi: 10.1002/mds.10541.
- BackgroundCoussement W, Van Cauteren H, Vandenberghe J, et al. Toxicological profile of hydroxypropyl Beta-cyclodextrin (HP-Beta-CD) in laboratory animals. In: Minutes of the Fifth International Symposium on cyclodextrins; 28-30 March 1990; Paris, France: Editions de Santé; 1990 p. 522-4.
- Background: PubMed 19750228Davidson CD, Ali NF, Micsenyi MC, Stephney G, Renault S, Dobrenis K, Ory DS, Vanier MT, Walkley SU. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS One. 2009 Sep 11;4(9):e6951. doi: 10.1371/journal.pone.0006951.
- Background: PubMed 11733542Dietschy JM, Turley SD. Control of cholesterol turnover in the mouse. J Biol Chem. 2002 Feb 8;277(6):3801-4. doi: 10.1074/jbc.R100057200. Epub 2001 Dec 3. No abstract available.
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- Individual participant dataSharing planned: Undecided
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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.
Caroline Hastings, MD principal investigator
Oakland CA
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydroxypropyl-beta-cyclodextrin in people with Niemann-Pick Disease, Type C1, run by Cyclo Therapeutics, Inc. at 2 sites 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 12 inclusion and 12 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 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Maximum Concentration ( C max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels (time frame: Pre- infusion then 2 ,4,6,8,8.5,9,10,11 12,16 and 20 hours after the start of the infusions at 1&12 w). The study lists 4 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 NCT02939547, which also lists 33 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 21 Feb 2021.