Safety and Efficacy of Intravenous Trappsol Cyclo (HPBCD) in Niemann-Pick Type C Patients

NCT02912793 | Completed Phase 1

• 1 other identifier: CTD-TCNP-201
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 5

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 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) 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 CSF.examinations 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.

Conditions

Niemann-Pick Disease, Type C1

Outcome Measures

Primary Outcomes (4)

• To evaluate the plasma the Maximum Concentration (C max) of 3 doses of Trappsol by measurement of plasma levels

  To evaluate plasma PK of Trappsol by comparison of Maximum Concentration (Cmax ) of the three doses

  0,2,4,6,& 8 hours (h) after the start of the IV infusion of Trappsol and 0.5,1,2,4,8 & 12 h after the end of the infusion

• To evaluate the Time to Maximum Concentration ( Tmax) of 3 doses of Trappsol by measurement of plasma levels

  To evaluate the plasma PK of Trappsol by comparison of the Tmax of three doses

  0,2,4,6,& 8h after the start of IV infusion of Trappsol and 0.5,1,2,4,6 &12h after the end of infusion

• To evaluate the Volume of Distribution of Trappsol by measurement of plasma levels

  To evaluate the plasma PK of Trappsol by comparison of the Volume of Distribution of three doses

  ),2,4,6 & 8 h after the start of the IV infusion of Trappsol and 0.5,1,2,4,8,&12 h after the end of the infusion

• To evaluate the elimination half-life of Trappsol by measurement of plasma levels

  To evaluate the PK of Trappsol by comparison of the Elimination half-lives of three doses

  0,2,3,6 & 8h after the start of IV infusion of Trappsol and 0.5,1,2,4,8 &12h after the end of infusion

Secondary Outcomes (9)

• Markers of cholesterol metabolism

  Screening,Days1,2,3,5,8,Weeks 2,4,8,10,12,14,16,18,20,24,28,32,36,40,44,48 and follow-up

• CSF levels of HP-β-CD

  Pre then 4,8,and 12h after the start of the initial infusion

• Number of patients with treatment-related adverse events as assessed by CTCAE ( version 4.03)

  Screening,Days1,2,3,4,6,8,Week 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48 and follow-up

• Abdominal ultrasound

  Baseline 12,24,36 and 48 weeks

• The proportion of patients with a reduction from baseline in the NIH NPC severity scale

  Baseline and 48weeks

Other Outcomes (2)

• Change from baseline in hepatic fractionated cholesterol

  Baseline , day 2 and 48weeks

• Exploratory measures of potential CSF Biomarkers

  Baseline, weeks 24and 48

Study Arms (3)

Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg

ACTIVE COMPARATOR

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

Drug: Hydroxypropyl-beta-cyclodextrin

Hydroxy-propyl-beta-cyclodextrin IV 2000 mg/kg

ACTIVE COMPARATOR

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

Drug: Hydroxypropyl-beta-cyclodextrin

Interventions

Hydroxypropyl-beta-cyclodextrin DRUG

Used in the treatment of Niemann-Pick C1

Also known as: Trappsol Cyclo

Hydroxy-propyl-beta-cyclodextrin IV 2000 mg/kg; Hydroxypropyl-beta-cyclodextrin IV 1500 mg/kg; Hydroxypropyl-beta-cyclodextrin IV 2500 mg/kg

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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 genotyping
• One NPC-1 mutation and positive filipin staining (current or prior)
• Vertical supranuclear gaze palsy \[VSNGP\] 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: 2 years upwards
• Negative pregnancy test for females of child bearing potential
• Written, informed consent

You may not qualify if:

• The presence of NPC-2 mutations on genotyping
• Previous receipt of cyclodextrin therapy
• Lanksy score \< 50 if aged ≤16 or Karnofsky score \< 40 if aged \> 16.
• Inability to comply with the proposed protocol assessments
• Concurrent treatment with any type of cholesterol lowering agents such as statins, fibrates, ezetimibe
• Concurrent medical conditions representing a contraindication to any of the study medications
• Stage 3 renal impairment or worse as indicated by eGFR\< 60mL/min using the MDRD equation
• 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
• Weight \>100 kg
• Females of childbearing potential who are not willing to use a method of highly effective contraception (hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, or true abstinence) during the study and the follow-up period. True abstinence can only be in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.
• Females who are breastfeeding

Sponsors & Collaborators

• Cyclo Therapeutics, Inc.: lead

Study Sites (5)

Soroka Mc

Beersheba, Rager Blvd, 85025, Israel

Location

HaeMek MC

Afula, 1834111, Israel

Location

Karolinska Trial Alliance

Solna, Huddinge, 141 76, Sweden

Location

Salford Royal Hospital

Salford, Greater Manchester, M6 8HD, United Kingdom

Location

Leonard Wolfson Experimental Neurology Centre

London, WC1N 3BG, United Kingdom

Location

Related Publications (31)

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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

• Reena Sharma, MB BS

  Salford Royal Foundation NHS Trust,

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 23, 2016
• Study Start: March 20, 2017
• Primary Completion: March 3, 2021
• Study Completion: March 3, 2021
• Last Updated: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); SE (1); IL (2)