Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)

NCT02939547 | Completed Phase 1 FDA Drug

• 1 other identifier: CTD-TCNPC-101
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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. 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,.

Conditions

Niemann-Pick Disease, Type C1

Keywords

intravenous; cyclodextrin; compassionate; Trappsol

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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

  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.

  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

Secondary Outcomes (8)

• CSF levels of Trappsol

  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

  Screening, baseline,then at 2,4,8,12 and 14 weeks

• Potential CSF biomarkers of NPC1

  Baseline, then at 12 and 14 weeks

• Serum cholesterol precursors and metabolites

  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

  Baseline and 12 weeks

Other Outcomes (2)

• Hepatic elasticity

  Baseline and 14weeks

• Filipin signal intensity

  Baseline and 12weeks

Study Arms (2)

Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg

ACTIVE COMPARATOR

Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks

Drug: Hydroxypropyl-beta-cyclodextrin

Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg

ACTIVE COMPARATOR

Hydroxypropyl-beta-cyclodextrin administered by slow IV infusion for 8 - 9h every 2 weeks

Drug: Hydroxypropyl-beta-cyclodextrin

Interventions

Hydroxypropyl-beta-cyclodextrin DRUG

Used in the treatment of Niemann-Pick Disease C1 ( NPC1)

Also known as: Hydroxypropyl-beta-cyclodextrin (HP-β-CD)

Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg; Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of NPC-1 defined as one of the following
• Two NPC-1 mutations on exome gene sequencing
• One NPC-1 mutation and positive filipin staining (current or prior)
• Vertical supranuclear gaze palsy \[VSGP\] plus either ≥ one NPC-1 mutation or positive filipin staining and no NPC-2 mutations
• NIH NPC Severity Score \<30 and with no more than 4 individual domains with a score ≥ 3.
• Age range: 18 years upwards
• At least one systemic manifestation of NPC disease defined as one or more of
• Clinically detectable hepatomegaly and/or either ALT or AST outside the normal range for the study laboratory
• Clinically detectable splenomegaly
• Impaired respiratory function due to NPC or a history of pneumonia in the last 12 months
• Negative urine pregnancy test for females of child bearing potential
• Written, informed consent

You may not qualify if:

• The presence of NPC-2 mutations on exome gene sequencing
• Previous receipt of cyclodextrin therapy within 3 months of baseline
• Receipt of any of the following medications within 1 month of baseline: Coenzyme Q10, curcumin, cinnamon, fish oil supplements, high dose vitamin D (\>500 milli-International unit (mIU)/day), acetyl leucine, or gingko biloba
• Concurrent treatment with any therapy indicated for the lowering of cholesterol such as statins, fibrates, ezetimibe
• Karnofsky score \< 40
• 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 patient assent)
• Concurrent medical conditions representing a contraindication to any of the study medications
• Grade 3 renal impairment or worse as indicated by eGFR\< 60mL/min/1.73m2
• Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or INR \>1.8
• Involvement in another interventional clinical trial within the previous 6 months from baseline
• Weight \<40 kg or \>100 kg
• Male patients and female patients of childbearing potential who are not willing to use appropriate birth control (i.e. double barrier birth control) from enrolment until the follow-up visit

Sponsors & Collaborators

• Cyclo Therapeutics, Inc.: lead

Study Sites (2)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Related Publications (33)

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  PMID: 36279795 DERIVED

MeSH Terms

Conditions

Niemann-Pick Disease, Type C

Interventions

2-Hydroxypropyl-beta-cyclodextrin

Condition Hierarchy (Ancestors)

Niemann-Pick Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

beta-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Dietary Carbohydrates; Carbohydrates; Glucans; Polysaccharides

Study Officials

• Caroline Hastings, MD

  Oakland CA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: October 20, 2016
• Study Start: October 11, 2017
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: February 21, 2021

Record last verified: 2021-02

Locations

US (2)