A study to review Wilson disease patients who have previously been prescribed d- Penicillamine but were changed to trientine as treatment for their disease, and to follow them for a further 12 months.

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2013-003564-31-IT
• Date of registration: 26/04/2018
• Prospective Registration: No
• Primary sponsor: UNIVAR LTD
• Public title: A study to review Wilson disease patients who have previously been prescribed d- Penicillamine but were changed to trientine as treatment for their disease, and to follow them for a further 12 months.
• Scientific title: Multicentre, Retrospective Study to Assess Long-Term Outcomes of Chelator-Based Treatment With Trientine in Wilson Disease Patients Withdrawn from Therapy With - N/A
• Date of first enrolment: 14/07/2016
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003564-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: Cross over: Other: yes Other trial design description: A m/c study with retrospective review of patients' medical records If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Greece, Italy, Spain, United Kingdom

Contacts

• Name: Trientine Enquiries
• Affiliation: Univar B.V.

• Name: Trientine Enquiries
• Affiliation: Univar B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients aged 1 year to 90 years of age
2. Physician-established diagnosis of Wilson disease based on a Ferenci score = 3
3. Documented treatment with d-Penicillamine, withdrawal of treatment with d-Penicillamine, followed by treatment with trientine for at least 6 months at date of informed consent
4. Able/willing to provide written informed consent.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Incomplete history of medication use for trientine from initial diagnosis to last follow-up
2. Unavailable outcome data for hepatic and neurological course of disease at all assessment time points
3. Patients with acute liver failure and fulminant hepatic disease with fatal outcome.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Wilson disease, also known as hepatolenticular degeneration, a rare automsomal, recessively inherited disorder which results in chronic copper intoxication.
MedDRA version: 20.0 Level: PT Classification code 10019819 Term: Hepato-lenticular degeneration System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Trientine dihydrochloride 300mg capsules
Pharmaceutical Form: Capsule, hard

Primary Outcome(s)

Main Objective: Assess the clinical course of Cu stores, neurological disease, and hepatic disease following initiation of treatment with trientine following withdrawal of d-Penicillamine. Retrospective data will be collected from visits at 6, 12, 24, 36 and 48 months, and at the last available follow up and will be based on the Investigator's score (unchanged, improved but not normal, improved to normal, asymptomatic over duration, and worsened).

Primary end point(s): Efficacy Endpoints: The clinical course of neurological and hepatic disease for each time point available after initiation of treatment (6, 12, 24, 36, and 48 months, and at the last available time point while taking second line trientine) will be scored (Investigator’s score) based on the status at the time of initiating trientine as: 1 = Unchanged 2 = Improved but not normal 3 = Improved to normal 4 = Asymptomatic over duration of therapy 5 = Worsened. ? The clinical course of hepatic disease at 6, 12, 24, 36, and 48 months and at the last available time point while taking second line trientine, based on the Investigator’s score and based on hepatic status at the time of initiating trientine ? The clinical course of neurological disease at 6, 12, 24, 36, and 48 months and at the last available time point while taking second line trientine, based on the Investigator’s score and based on neurological status at the time of initiating trientine ? Cu storage and metabolism, measured at 6, 12, 24, 36, and 48 months and at the last available time point after initiating second line trientine therapy, by available tests, eg, 24-hour urinary Cu excretion, serum ceruloplasmin (CPN), and Serum Cu, compared to Cu storage values at the time of initiating trientine. Overall duration of treatment, defined as time to discontinuation of treatment due to AEs and/or inadequate response, will be assessed after initiation of trientine. ? Time to discontinuation of trientine due to AEs ? Time to discontinuation of trientine due to inadequate response measured by poor clinical outcome (failure to stabilise or reverse signs and symptoms) where: o Inadequate hepatic response is defined by: ? Progression to liver transplant ? Increase of at least 2 of 3 liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyltranspeptidase [GGT]) = 2 x normal or = 2 x baseline ? Increase of 24-hour urinary Cu excretion when collected in 2 consecutive measurements o Inadequate neurological response is defined by neurological deterioration (physician’s decision). ? Patient treatment status at the last available time point: o Treatment status o If trientine stopped: ? Reason for discontinuing ? When trientine discontinued o What new treatment prescribed. Safety Endpoint: ? Adverse events related to trientine treatment and AEs leading to discontinuation of trientine will be assessed at each available study time point.

Secondary Objective: - Assess the safety of trientine treatment based on reported adverse events (AEs), including AEs leading to discontinuation of treatment with trientine
- Determine duration of treatment with second line therapy trientine, defined as time to discontinuation of treatment due to AEs and/or inadequate response.

This study aims to show that trientine is likely to be better tolerated without compromising effective treatment management of Wilson disease when given 2nd line to d-Penicillamine.

Timepoint(s) of evaluation of this end point: The time point available after initiation of treatment (6, 12, 24, 36 and 48 months), and at the last available time point while taking second line trientine.

Secondary Outcome(s)

Secondary end point(s): N/A

Timepoint(s) of evaluation of this end point: N/A

Secondary ID(s)

NCT02426905

UNV-TRI-002

2013-003564-31-DE

N/A

ISRCTN00000000

Source(s) of Monetary Support

Univar B.V