Niemann-Pick disease type C MedDRA version: 20.0 Level: PT Classification code 10029403 Term: Niemann-Pick disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Trappsol Cyclo
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: hydroxypropyl-beta-cyclodextrin
CAS Number: 128446-35-5
Sponsors
CTD Holdings, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Confirmed diagnosis of NPC-1 defined as one of the following: a) Two NPC-1 mutations on genotyping b) One NPC-1 mutation and positive filipin staining (current or prior) c) Vertical supranuclear gaze palsy [VSNGP] plus either = one NPC-1 mutation or positive filipin staining and no NPC-2 mutations 2. NIH NPC Severity Score =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The presence of NPC-2 mutations on genotyping 2. Previous receipt of cyclodextrin therapy 3. Lanksy score 16. 4. Inability to comply with the proposed protocol assessments 5. Concurrent treatment with any type of cholesterol lowering agents such as statins, fibrates, ezetimibe 6. Concurrent medical conditions representing a contraindication to any of the study medications 7. Stage 3 chronic kidney disease (CKD) or worse as indicated by an eGFR 18 years eGFR is calculated using the MDRD equation 8. Clinical evidence of acute liver disease including symptoms of jaundice or right upper quadrant pain or international normalised ratio (INR) >1. 8 9. Involvement in another interventional clinical trial within the previous 6 months from screening 10. Weight >100 kg 11. 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 sexual abstinence) during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: See Section E.5.1; Main Objective: Stage 1 • To compare the plasma pharmacokinetics of hydroxypropyl-ß-cyclodextrin following 3 different single doses of intravenous Trappsol Cyclo in patients with NPC-1 Stage 2 • To evaluate the efficacy and tolerability of 3 different doses of Trappsol Cyclo in the management of clinical manifestations of NPC-1 ; Secondary Objective: Stage 1 • To investigate the effect of 3 different doses of intravenous Trappsol Cyclo in patients upon serum and lymphocytic markers of cholesterol metabolism in patients with NPC-1 • To evaluate hydroxypropyl-ß-cyclodextrin concentrations in cerebrospinal fluid following intravenous administration of Trappsol Cyclo in patients with NPC-1 Stage 2 • To investigate the effect of 3 different doses of intravenous Trappsol Cyclo upon serum and lymphocytic markers of cholesterol metabolism in patients with NPC-1 • To evaluate the impact of treatment upon measures of neurological function including ataxia, cognitive impairment, fine motor skills and saccadic eye movements in patients with NPC-1 • To evaluate the impact of treatment upon behavioural aspects of NPC-1 disease ; Primary end point(s): Stage 1 • Plasma concentrations of HP-ß-CD during and following infusion to evaluate Tmax, Cmax, volume of distribution and elimination half-life (at 0, 2, 4, 6 and 8 hours after the start of infusion and 30 minutes, 1, 2, 4, 8 and 12 hours after the end of the infusion) Stage 2 • Change from baseline in global impression of disease severity at 48 weeks • The proportion of patients at 48 weeks with a reduction from baseline of at least one point in two or more domains of the NIH NPC severity | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 1 • Change from baseline in serum cholesterol precursors (lanosterol, lathosterol, desmosterol) and cholesterol metabolites/bile acid precursors (4b-, 24S-, 25-, 27- hydroxycholesterol) (days 2, 3, 5, 8, and 15 post-dose in Stage 1) • Change from baseline in markers of lipid trafficking in peripheral blood mononuclear cells (PBMCs) (at day 15 post-dose in Stage 1) • CSF concentrations of HP-ß-CD at 4, 8 and 12 hours following the start of the intravenous administration. In paediatric patients the number of samples may be reduced at the discretion of the Investigator to one post dose sample taken approximately within 1 hour after the end of the infusion. (Stage 1) • AEs, laboratory abnormalities, time to withdrawal due to AE (every visit) Stage 2 • Change from baseline in serum cholesterol precursors (lanosterol, lathosterol, desmosterol) and cholesterol metabolites/bile acid precursors (4b-, 24S-, 25-, 27- hydroxycholesterol) (4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 weeks) • Change from baseline in markers of lipid trafficking in peripheral blood mononuclear cells (PBMCs) (12, 24, 36 and 48 weeks) • Change from baseline in NIH NPC severity scale at 12, 24, 36 and 48 weeks • Change from baseline in individual NIH NPC scale domains at 12, 24, 36 and 48 weeks • Change from baseline in neurologic symptoms at 12, 24, 36 and 48 weeks - ataxia (using the Scale for the assessment and rating of ataxia [SARA] scale)* - cognitive impairment (using the Mini-Mental State Evaluation score [MMSE])* - saccadic eye movements - fine motor skills (using the bead threading test)* *In patients where age and cognitive function allow • Change from baseline in hepatic, splenic and renal morpho | — |
Countries
Italy, Sweden, United Kingdom
Contacts
Public ContactSenior VP for Medical Affairs
CTD Holdings, Inc.
Outcome results
None listed