Ignite Creation Date:
2024-05-06 @ 9:08 AM
Last Modification Date:
2024-10-26 @ 12:10 PM
Study NCT ID:
NCT02912793
Status:
COMPLETED
Last Update Posted:
2021-08-10
First Post:
2016-08-19
Brief Title:
Safety and Efficacy of Intravenous Trappsol Cyclo HPBCD in Niemann-Pick Type C Patients
Sponsor:
Cyclo Therapeutics Inc
Organization:
Cyclo Therapeutics Inc
Study Overview
Official Title:
A Phase III Study to Evaluate the Safety and PK of iv Trappsol Cyclo HP-β-CD in Patients With Niemann-Pick Disease Type C NPC-1 and the Pharmacodynamic Effects of Treatment Upon Markers of Cholesterol Metabolism and Clinical Outcomes
Status:
COMPLETED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This research study is being conducted to find out whether Trappsol Cyclo an experimental treatment for people with Niemann-Pick disease Type C1 NPC-1 is safe at 3 different dose levels and what effects it has on people who have this condition NPC-1 is caused by a defect in a 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 56 weeks in total recruitment is expected to take 9 monthsPatients 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 are also taken by lumbar puncture during and following the first treatment dose 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 Optional assessments patients can choose to take part in include liver biopsies additional lumbar punctures for CSFexaminations to see if the drug is affecting these This study is being sponsored and funded by CTD holdings INC It is planned to be run in the UK Italy and Sweden
Detailed Description:
The planned study has been designed as a Phase III double-blind randomised multi-centre parallel group study based on information and data available from the administration of Trappsol Cyclo via compassionatenamed patient use in patients with NPC-1 and data on other cyclodextrin products in the scientific literature
The study is comprised of two stages The primary objective of Stage 1 is to compare the plasma pharmacokinetics of three different doses of IV Trappsol Cyclo in the prevention delay of NPC-1 progressionSecondary objectives include investigation of the Hydroxypropyl Beta Cyclodextrin HP-β-CD effect of three different doses of IV Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism Stages 1 and 2 and evaluation of concentrations in the cerebrospinal fluid CSF following intravenous IV administration Stage 1 evaluation of the impact of treatment upon measures of neurological function including ataxia aphasia and saccadic eye movements and the impact of treatment upon behavioural aspects of NPC-1 Stage 2
It is planned to recruit a total of 12 patients to the study Patients will be randomised 111 to one of the three dose levels 1500 mgkg 2000 mgkg or 2500 mgkg four patients per dose level Treatment will be administered every two weeks by slow IV infusion at a concentration of 250 mgmL over 8 hours Patients completing Stage 1 of the study will continue into Stage 2 and receive treatment for 48 weeks Patients who withdraw prior to completion of the initial pharmacokinetic PK and pharmacodynamics PD assessments will be replaced
The design of the proposed study thus enables early assessment of biochemical markers of response but allows for a sufficient dosing duration to enable the effectiveness of Trappsol in NPC-1 to be assessed
As miglustat is an approved treatment for NPC-1 in the EU with an established efficacy and safety profile it would be unethical to exclude patients receiving miglustat therapy from the study given that the study itself will also be conducted at sites in Europe However it is planned to balance randomisation across the treatment groups for its use
The maximum dose proposed for this study is below the maximum dose for which long term clinical data is available in 2 patients 2800 mgkg weekly for 3-5 years Although individual clinicians have not always utilised 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 metabolismturnover in the mouse is 13-fold higher than in man which in NPC-1 likely translates into a 13-fold slower accumulation of cholesterol in human cells compared with those of the mouseTherefore it is theorised 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 minimises the amount of infusions required to be administered
The study is comprised of two stages The primary objective of Stage 1 is to compare the plasma pharmacokinetics of three different doses of IV Trappsol Cyclo in the prevention delay of NPC-1 progressionSecondary objectives include investigation of the Hydroxypropyl Beta Cyclodextrin HP-β-CD effect of three different doses of IV Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism Stages 1 and 2 and evaluation of concentrations in the cerebrospinal fluid CSF following intravenous IV administration Stage 1 evaluation of the impact of treatment upon measures of neurological function including ataxia aphasia and saccadic eye movements and the impact of treatment upon behavioural aspects of NPC-1 Stage 2
It is planned to recruit a total of 12 patients to the study Patients will be randomised 111 to one of the three dose levels 1500 mgkg 2000 mgkg or 2500 mgkg four patients per dose level Treatment will be administered every two weeks by slow IV infusion at a concentration of 250 mgmL over 8 hours Patients completing Stage 1 of the study will continue into Stage 2 and receive treatment for 48 weeks Patients who withdraw prior to completion of the initial pharmacokinetic PK and pharmacodynamics PD assessments will be replaced
The design of the proposed study thus enables early assessment of biochemical markers of response but allows for a sufficient dosing duration to enable the effectiveness of Trappsol in NPC-1 to be assessed
As miglustat is an approved treatment for NPC-1 in the EU with an established efficacy and safety profile it would be unethical to exclude patients receiving miglustat therapy from the study given that the study itself will also be conducted at sites in Europe However it is planned to balance randomisation across the treatment groups for its use
The maximum dose proposed for this study is below the maximum dose for which long term clinical data is available in 2 patients 2800 mgkg weekly for 3-5 years Although individual clinicians have not always utilised 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 metabolismturnover in the mouse is 13-fold higher than in man which in NPC-1 likely translates into a 13-fold slower accumulation of cholesterol in human cells compared with those of the mouseTherefore it is theorised 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 minimises the amount of infusions required to be administered
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None