Clinical Trial: Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
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
Brief 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. 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. Samples of cerebrospinal fluid (CSF) will be taken by lumbar puncture during and following the first and subsequent treatment 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 Summary:
The planned study has been designed as a Phase I, double-blind, randomised, single-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 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.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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) ]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
- Potential blood biomarkers of NPC1 [ Time Frame: Screening, baseline,then at 2,4,8,12 and 14 weeks ]To investigate the effect of 2 different doses of intravenous Trappsol upon peripheral blood biomarkers of NPC-1 disease
- Potential CSF biomarkers of NPC1 [ Time Frame: Baseline, then at 12 and 14 weeks ]To investigate the effect of 2 different doses of intravenous Trappsol upon biomarkers of NPC-1 disease in CSF
- 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) ]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
- Fractionated cholesterol in hepatic tissue [ Time Frame: Baseline and 12 weeks ]To investigate the effect of 2 different doses of intravenous Trappsol in patients with NPC-1 disease upon fractionated cholesterol in hepatic tissue
- Splenic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores [ Time Frame: Baseline then 14 weeks ]To evaluate the effect of 2 different doses of Trappsol upon change in clinical manifestations of NPC-1 disease
- Hepatic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores [ Time Frame: Baseline then 14 weeks ]To evaluate the effect of 2 different doses of Trappsol upon change in clinical manifestations of NPC-1 disease
- 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 ]Events will be gathered by spontaneous reporting, clinical observation and laboratory tests including auditory tests and auditory evoked potentials to assess hearing
Original Secondary Outcome: Same as current
Information By: CTD Holdings, Inc.
Dates:
Date Received: September 21, 2016
Date Started: April 28, 2017
Date Completion: December 2017
Last Updated: March 28, 2017
Last Verified: March 2017
