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: 27 August 2018
• Main ID: EUCTR2013-003564-31-DE
• Date of registration: 22/10/2013
• Prospective Registration: Yes
• Primary sponsor: Univar B.V.
• 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 and Prospective Study to Assess Long Term Outcomes of Chelator-Based Treatment With Trientine in Wilson Disease Patients Withdrawn from Therapy With d-Penicillamine
• Date of first enrolment: 27/02/2014
• 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: no; Cross over: no; Other: yes; Other trial design description: A m/c study with retrospective review of patients' medical records and an optional prospective part; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany, Italy

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients aged 1 year to 90 years of age at initiation of treatment with trientine.
- Physician established diagnosis of Wilson disease based on a Ferenci score > 3 at the date of diagnosis.
- 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.
- Able/willing to provide written informed consent.

For enrolment in the prospective part:
- Enrolment in the retrospective part of the study.
- On-going treatment with trientine.
- Negative pregnancy test.
- Able/willing to provide written informed consent.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
- Incomplete history of medication use for trientine from initial diagnosis to latest follow up.
- Unavailable outcome data for hepatic and neurological course of disease at initiation of treatment with trientine and at least 1 time point post-initiation of treatment with trientine.

For enrolment in the prospective part:
- Hypersensitivity to trientine
- Severe anaemia.



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

Health Condition(s) or Problem(s) studied

Wilson disease, also known as hepatolenticular degeneration, a rare automsomal, recessively inherited disorder which results in chronic copper intoxication.
MedDRA version: 19.1 Level: LLT Classification code 10047988 Term: Wilson's disease System Organ Class: 100000004850

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

Intervention(s)

Trade Name: Trientine dihydrochloride 300mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TRIENTINE DIHYDROCHLORIDE
CAS Number: 38260-01-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

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. For the prospective part, this will be the 12 month visit.

Secondary Objective: For the prospective part of the study:
- Determine the proportion of patients with stable disease according to the Investigator's score after 12 months of treatment with trientine.
- Assess the course of the hepatic disease.
- Assess the course of disease according to the neurologic subscore of the Unified Wilson Disease Rating Scale (UWDRS).
- Assess serum and urinary parameters of copper metabolism.
- Assess quality of life (QoL).

Primary end point(s): - 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 initiation of treatment with trientine, by available tests, for example,
*24 hour urinary Cu excretion
*Serum CPN
*Serum Cu
compared to Cu storage values at the time of initiation of treatment with trientine.

- Time to discontinuation of trientine due to AEs
- Time to discontinuation of trientine due to inadequate response measured by poor clinical outcome
- Time to discontinuation of trientine due to AEs and/or inadequate response measured by poor clinical outcome
- Patient treatment status at last available timepoint

For the prospective part - The clinical course of neurological and hepatic disease will be scored (Investigator's score) based on status at 6 and 12 months after Baseline. A patient will be counted as a responder if they have a rating of 1-4 at the 12 month visit for both neurological and hepatic Investigator's score. They will be counted as a non-responder if they have a rating of 5 for one or both scores at the 12 month visit or if they were discontinued from the study for any reason prior to the 12 month visit.

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 after initiation of treatment, and at the last available follow up visit. Assessments will be based on the Investigator’s score (unchanged, improved but not normal, improved to normal, asymptomatic over duration, and worsened). Prospective assessments will be performed at Baseline (enrolment) and at 6 months and 12 months following the Baseline visit.
- Assess the safety of trientine treatment based on reported 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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The 6 month and 12 month visits.

Secondary end point(s): For the prospective part:-
- The clinical course of hepatic disease at 6 and 12 months while taking second line trientine, based on the Investigator’s score and based on hepatic status at the time of enrolment into prospective part in terms of:
*AST to Platelet Ratio Index (APRI) based on AST, gender, and platelet count
*Child-Pugh Score based on INR, total bilirubin, albumin, hepatic encephalopathy, and esophageal varices
*FIB4 based on age, ALT, AST, and platelets
*Model for End-Stage Liver Disease (MELD) based on INR, total bilirubin, creatinine, and sodium
*Modified Nazer Score based on albumin, AST, total bilirubin, INR, and leukocytes
*Fibroscan.
- The clinical course of neurological disease at 6 and 12 months while taking second line trientine, based on the Investigator’s score and based on neurological status at the time of enrolment into prospective part.
- The neurologic subscore of the UWDRS at Baseline, 6 and 12 months.
- Cu storage and metabolism, measured at 6 and 12 months after initiating second line trientine therapy, by available tests, e.g., 24-hour urinary Cu excretion, serum CPN, and Serum Cu, compared to Cu storage values at the time of enrolment into prospective part.
- Quality of life questionnaires will be completed for each time point and data will be compared to baseline (prospective part) after 6 and 12 months.

Secondary ID(s)

UNV-TRI-002

Source(s) of Monetary Support

Univar B.V.