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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Niemann-Pick Disease, Type C1
• Intervention / Treatment: Drug: Hydroxypropyl-β-cyclodextrin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxypropyl-β-cyclodextrin IV; 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; 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.; Other Names: Hydroxypropyl-β-cyclodextrin (HP-β-CD); Trappsol® Cyclo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cyclo Therapeutics, Inc.
• Investigators: Principal Investigator: Caroline Hastings, MD, UCSF Benioff Children's Hospital Oakland

Publications and helpful links

General Publications

• Hastings C, Liu B, Hurst B, Cox GF, Hrynkow S. Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial. Mol Genet Metab. 2022 Oct 17;137(4):309-319. doi: 10.1016/j.ymgme.2022.10.004. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Dementia; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Language Disorders; Communication Disorders; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: CTD-TCNPC-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No