Open-Label Study of Long-Term Safety and Efficacy of Intravenous Trappsol Cyclo (HPβCD) in Niemann-Pick Disease Type C

Study Overview
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Brief Summary
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The purpose of this study is to provide continued access to treatment for NPC-1 after participation and completion of the Phase I trial CTD-TCNPC-101, when administered at doses of 1500 mg/kg and 2500 mg/kg by slow IV infusion over a period of 8 to 9 hours every two weeks.

Detailed Description
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This is an open-label extension study of intravenous HP-β-CD (administered as Trappsol® Cyclo(TM)) in patients with NPC-1 to evaluate long-term safety and efficacy by providing continued access to treatment following completion of study CTD-TCNPC-101. Patients will receive medication at their home or local site under the supervision of a home nurse professional or at the parent site under the supervision of the site principal investigator. Patients will visit the parent site for safety and efficacy evaluations after receiving treatment for 3 months in the extension protocol. Thereafter, visits to the parent site will be every 6 months until cessation. The study will continue until Trappsol® Cyclo (TM) becomes commercially available or study/site/patient discontinuation. All patients who complete study CTD-TCNCP-101 and pass the screening criteria will be eligible for this study. The study will be directed from parent site in the US. Vital signs, AEs Adverse Events (AEs) and concomitant meds will be recorded by the home nurse professional or deputy at the local site and reported immediately to the parent site for entry into the Electronic Data Capture (EDC) and reporting to the sponsor. For logistical reasons home infusions will be permitted as long as AEs, infusion details and concomitants medications are reported directly to the parent site by an authorised deputy according to local guidelines. A Safety Review Committee (SRC) consisting of an independent advisor, the medical monitor, and the principal investigator will be established to review AEs and laboratory data throughout the study.

Official Title
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An Open-Label Extension Study of the Long-Term Safety and Efficacy of Intravenous Trappsol® Cyclo (HP-β-CD) in Patients With Niemann-Pick Disease Type C (NPC-1)

Conditions
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Niemann-Pick Disease, Type C1

Intervention / Treatment
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* Drug: Hydroxypropyl-β-cyclodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of study CTD-TCNPC-101 with no safety concerns at the final visit Negative urine pregnancy test for females of child bearing potential Patients must be legally resident in the USA with access to healthcare Written, informed consent Exclusion Criteria: 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 subject assent) Concurrent medical conditions representing a contraindication to any of the study medications Grade 3 renal impairment or worse as indicated by estimated Glomerular filtration rate (eGFR) < 60mL/min/1.73m2 Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or International Normalised Ratio (INR) >1.8 Male patients and female patients of childbearing potential who are not willing to use appropriate birth control (i.e. double barrier birth control) from enrollment until the follow-up visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxypropyl-β-cyclodextrin IV<br>Hydroxypropyl-β-cyclodextrin will be administered as Trappsol® Cyclo 25% (250mg/mL) by slow intravenous infusion over a period of 8 up to 9 hours. | Drug: Hydroxypropyl-β-cyclodextrin<br>* HP-β-CD will be administered as Trappsol® Cyclo 25% (250mg/mL) by slow intravenous infusion over a period of 8 up to 9 hours.<br>* Other names: Trappsol® Cyclo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product | Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product | 1-104 weeks | 
| Serious adverse events (SAEs): Frequency, severity, time to onset, duration and relatedness to study product | Serious adverse events (SAEs): Frequency, severity, time to onset, duration and relatedness to study product | 1-104 weeks | 
| Number of discontinuations due to AEs: Patient Discontinuation, Study Treatment Discontinuation, Study and Site Discontinuation | Discontinuation, Study and Site Discontinuation | 1-104 weeks | 
| Auditory capacity will be measured by behavioral auditory assessment | Auditory capacity will be measured by behavioral auditory assessment | 1-104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in total score as well as individual National Institute of Health (NIH) Niemann-Pick Disease Type C (NPC) Severity Scale (NCSS) | Change from baseline in total score as well as individual National Institute of Health (NIH) Niemann-Pick Disease Type C (NPC) Severity Scale (NCSS) | 1-104 weeks |