A Phase 1 interventional study of Hydroxypropyl-beta-cyclodextrin in Niemann-Pick Disease, Type C1, sponsored by Cyclo Therapeutics, Inc.. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-02-21.
Sponsored by Cyclo Therapeutics, Inc. · Phase 1, Interventional, and Basic science
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,.
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.
227 studies on the registry are indexed under Pick Disease of the Brain; 55 are open to participants now.
This study's enrollment of 13 is below the median of 34 across 138 interventional studies indexed under Pick Disease of the Brain.
Browse Pick Disease of the Brain studies →Cyclo Therapeutics, Inc. is the lead sponsor of 6 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Confirmed diagnosis of NPC-1 defined as one of the following
At least one systemic manifestation of NPC disease defined as one or more of
Exclusion Criteria:
Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks
Drug: Hydroxypropyl-beta-cyclodextrin
Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks
Drug: Hydroxypropyl-beta-cyclodextrin
Used in the treatment of Niemann-Pick Disease C1 ( NPC1)
Also known as: Hydroxypropyl-beta-cyclodextrin (HP-β-CD)
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
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
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
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
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
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
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.
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
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
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
To investigate the effect of 2 different doses of intravenous Trappsol upon peripheral blood biomarkers of NPC-1 disease
Time frame: 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
Time frame: 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
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
To investigate the effect of 2 different doses of intravenous Trappsol in patients with NPC-1 disease upon 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
To evaluate the effect of 2 different doses of Trappsol upon change in clinical manifestations of NPC-1 disease
Time frame: 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
Time frame: 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
Time frame: Screening, baseline, days 1, 2-11, weeks 2,4,6,810,12,14 and 18
Hepatic elasticity
To investigate the effect of 2 different doses of intravenous Trappsol upon hepatic elasticity (measured by ultrasound scan) at 14 weeks (after 7 doses) in patients with NPC-1 disease
Time frame: Baseline and 14weeks
Filipin signal intensity
To investigate the effect of 2 different doses of intravenous Trappsol on filipin signal intensity (measured in cultured fibroblasts collected by skin biopsy) at 14 weeks (after 7 doses) in patients with NPC-1 disease
Time frame: Baseline and 12weeks
Plan to share: Undecided
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Cyclo Therapeutics, Inc.