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

• Status: Completed
• Trial end date: 2020-02-10
• Target enrollment: 0
• Participant gender: All

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,.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CTD Holdings, Inc.; Cyclo Therapeutics, Inc.
• Treatments: Betadex

Criteria

Inclusion Criteria:

1. Confirmed diagnosis of NPC-1 defined as one of the following

1. Two NPC-1 mutations on exome gene sequencing

2. One NPC-1 mutation and positive filipin staining (current or prior)

3. Vertical supranuclear gaze palsy [VSGP] plus either ≥ one NPC-1 mutation or positive filipin staining and no NPC-2 mutations

2. NIH NPC Severity Score <30 and with no more than 4 individual domains with a score ≥ 3.

3. Age range: 18 years upwards

4. At least one systemic manifestation of NPC disease defined as one or more of

1. Clinically detectable hepatomegaly and/or either ALT or AST outside the normal range for the study laboratory

2. Clinically detectable splenomegaly

3. Impaired respiratory function due to NPC or a history of pneumonia in the last 12 months

5. Negative urine pregnancy test for females of child bearing potential

6. Written, informed consent

Exclusion Criteria:

1. The presence of NPC-2 mutations on exome gene sequencing

2. Previous receipt of cyclodextrin therapy within 3 months of baseline

3. 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

4. Concurrent treatment with any therapy indicated for the lowering of cholesterol such as statins, fibrates, ezetimibe

5. Karnofsky score < 40

6. 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)

7. Concurrent medical conditions representing a contraindication to any of the study medications

8. Grade 3 renal impairment or worse as indicated by eGFR< 60mL/min/1.73m2

9. Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or INR >1.8

10. Involvement in another interventional clinical trial within the previous 6 months from baseline

11. Weight <40 kg or >100 kg

12. 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