Wilson Disease MedDRA version: 22.1 Level: PT Classification code 10019819 Term: Hepato-lenticular degeneration System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Univar Solutions, B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient (or a representative) must provide written, informed consent before the start of any study procedures. 2. Male and female patient aged = 5 years at time of consent. 3. Diagnosis of WD previously determined by the physician based on a Leipzig score = 4. 4. Patient (= 18 years) has previously been treated with D-penicillamine for WD. 5. Patient (=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Patient has evidence of uncontrolled liver disease, including but not limited to: a. New Wilson index (Dhawan Index) > 10 b. Alanine aminotransferase (ALT) > 5x upper limit of normal (ULN) c. Aspartate aminotransferase (AST) > 5x ULN d. MELD score > 13 (only applicable for patients that are = 12 years of age) e. Acute liver failure f. Hepatic malignancy 2. Uncontrolled neurological disease according to the judgement of the physician. 3. Patient has severe anaemia defined as hemoglobin of < 9 g/dL. 4. Patient has a known intolerance, allergy or sensitivity to trientine dihydrochloride, including any component of the study medication. 5. Female patient is pregnant or lactating. 6. Any patients who lack the capacity to consent including the parent(s) of a paediatric patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the Cufence dose – exposure – copper markers (24-h urinary copper excretion (UCE), total serum copper, ceruloplasmin bound copper, non-ceruloplasmin bound copper (NCC)) relationships through population pharmacokineticpharmacodynamic (PKPD) modelling in Wilson’s disease (WD) patients and to evaluate the influence of patient characteristics on relevant model parameters, such as apparent clearance, apparent volume of distribution and drug potency.;Secondary Objective: • To investigate the contribution of trientine, N(1)-acetyltriethylenetetramine (MAT) and N(1),N(10)-diacetyltriethylenetetramine (DAT) to the exposure and copper markers (exposure-response) in patients with Wilson’s disease. • To investigate the relationship between Cufence exposure (systemic trientine, MAT and DAT) and clinical efficacy measures (changes in neurological disease, changes in psychiatric symptoms and changes in hepatic disease) in patients with Wilson’s disease. • To investigate the relationships between copper markers (24-h UCE, total serum Cu, ceruloplasmin bound copper, NCC and clinical efficacy measures (changes in neurological disease, changes in psychiatric symptoms and changes in hepatic disease) in patients with Wilson’s disease. • To investigate the safety and tolerability of Cufence in patients with Wilson’s disease.;Primary end point(s): • Concentration of trientine in plasma • Trientine clearance (CL/F) and volume(s) of distribution (V/F) • 24-h UCE (copper marker) • NCC* (copper marker) • Serum copper (copper marker) • Serum ceruloplasmin (copper marker) • Patient characteristics for covariates ;Timepoint(s) of evaluation of this end point: • Concentration of trientine in plasma at Visit 2- Visit 10 • Trientine clearance (CL/F) and volume(s) of distribution (V/F) at Visit 2- Visit 10 except Visit 5 • 24-h UCE (copper marker)at Visit 2- Visit 10 except Visit 5 • NCC* (copper marker) at Visit 2- Visit 10 except Visit 5 Serum copper (copper marker | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Concentration of MAT in plasma • Concentration of DAT in plasma • AUC0-t, Cmax and Ctrough for trientine and metabolites. (As secondary endpoint, pre-dose concentrations are reported and summarized using NCA. While the pre-dose PK samples are collected shortly prior to the next dose, the pre-dose concentration is assumed to approximate the Ctrough.) • Number of AEs including number of AEs leading to discontinuation of treatment with Cufence • Changes in neurological disease status (Unified Wilson’s Disease Rating Scale (UWDRS)) • Changes in psychiatric symptoms (SCID-5, MMSE, EQ-5D-3L, PHQ-9, PHQ-9-A, CBCL) • Changes in hepatic disease (full liver panel to determine the APRI, the Child-Pugh score, the FIB4 index and the New Wilson Index (Dhawan Index), and Fibroscan) ;Timepoint(s) of evaluation of this end point: • Concentration of MAT in plasma at Visit 2- Visit 10 • Concentration of DAT in plasma at Visit 2- Visit 10 • AUC0-tau, Cmax and Cmin for trientine and metabolites (by NCA) at Visit 2- Visit 10 except Visit 5 • Number of AEs including number of AEs leading to discontinuation of treatment with Cufence at all visits • Changes in neurological disease status (Unified Wilson’s Disease Rating Scale (UWDRS)) at Visit 2,4 and Visit 6-10 • Changes in psychiatric symptoms (SCID-5, MMSE, EQ-5D-3L, PHQ-9, PHQ-9-A, CBCL)-various timepoint for each assessment • Changes in hepatic disease (full liver panel to determine the APRI, the Child-Pugh score, the FIB4 index and the New Wilson Index (Dhawan Index), and Fibroscan) | — |
Countries
Denmark, France, Germany, Poland
Contacts
Public ContactKarin Flicker
QPS Clinical Services GmbH
Outcome results
None listed