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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 March 2021
• Main ID: NCT02939547
• Date of registration: 21/09/2016
• Prospective Registration: Yes
• Primary sponsor: Cyclo Therapeutics, Inc.
• Public title: Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)
• Scientific title: A Phase I Study to Evaluate the Single and Multiple-dose Pharmacokinetics of Intravenous Trappsol Cyclo (HP-Beta-CD) in Patients With Niemann-Pick Disease Type C (NPC-1) and the Effects of Dosing Upon Biomarkers of NPC Disease
• Date of first enrolment: October 11, 2017
• Target sample size: 13
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02939547
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Caroline Hastings, MD
• Affiliation: Oakland CA

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Niemann-Pick Disease, Type C1

Intervention(s)

Drug: Hydroxypropyl-beta-cyclodextrin

Primary Outcome(s)

Volume of Distribution of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels [Time Frame: 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]

Maximum Concentration ( C max) of Trappsol in plasma from patients with Niemann-Pick disease Type C1 by measurement of plasma levels [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 Outcome(s)

CSF levels of Trappsol [Time Frame: Pre-infusion then 2,4,6,8,12 hours after the first infusion ( w1) and 8h after the start of the last infusion (W12)]

Fractionated cholesterol in hepatic tissue [Time Frame: Baseline and 12 weeks]

Potential CSF biomarkers of NPC1 [Time Frame: Baseline, then at 12 and 14 weeks]

Hepatic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores [Time Frame: Baseline then 14 weeks]

Number of patients with treatment-related adverse events as graded by CTCAE criteria ( Version 4.03) [Time Frame: Screening, baseline, days 1, 2-11, weeks 2,4,6,810,12,14 and 18]

Splenic morphology assessed by qualitative change in ultrasound compared with baseline, NIH total and individual domain severity scores [Time Frame: Baseline then 14 weeks]

Serum cholesterol precursors and metabolites [Time Frame: 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)]

Potential blood biomarkers of NPC1 [Time Frame: Screening, baseline,then at 2,4,8,12 and 14 weeks]

Secondary ID(s)

CTD-TCNPC-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors