Chelate Study: Trientine for the treatment of Wilson's disease

Phase 1

Conditions: Wilson's disease (WD) is a life-threatening inborn error of copper metabolism leading to an excessive copper accumulation, mainly in the liver or brain, causing hepatic and neurologic severe symptoms.
MedDRA version: 20.0Level: LLTClassification code 10047988Term: Wilson's diseaseSystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2016-003876-29-IT

Lead Sponsor: GMP ORPHAN SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 55

Inclusion Criteria

1. Patient is able to provide and has provided written informed consent has been obtained
2. Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable, including for EU sites, Data Protection Consent
3. Male or female, aged = 18 and = 75 years old at time of consent
4. Patient has a diagnosis of Wilson’s disease, as defined by a prior or current Leipzig score of = 4
5. Patient’s Wilson’s disease is clinically stable, in the opinion of the investigator, and being treated with penicillamine for at least 1 year (52 weeks) prior to the screening visit
6. Patient is on a stable dose and regimen of penicillamine for at least 4 months (16 weeks) prior to the screening visit (other prescribed treatments for Wilson’s disease not permitted during this period)
7. No anticipated need that patient will require additional pharmacological therapies other than study medication, including prescribed zinc therapy, for the management of copper levels during the study
8. Patient must be willing to maintain stable diet throughout the study, and avoid foods with high copper content, including the screening period
9. Patient considered suitable to receive therapy with both TETA 4HCl and penicillamine administered twice a day
10. Negative central laboratory tests for HIV and viral hepatitis (results will be available after start of run-in period)
11. For female patients of childbearing potential, negative urine pregnancy test (at screening visit and prior to randomization)
12. For females of childbearing potential, use of a reliable form of contraceptive
13. Patient is considered as able to complete study requirements and attend the study visits, in he opinion of the investigator
Are the trial subjects under 18? no
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. Patient is in ‘de-coppering’ phase of treatment for Wilson’s disease, in the opinion of the investigator
2. Patient evidence of uncontrolled liver disease, including but not limited to:
a. Modified Nazer score of = 4 (result may not be available until after start of run-in period on lab results*)
b. decompensated cirrhosis
c. acute hemolytic anemia
d. acute hepatitis
e. hepatic malignancy
f. evidence of acute liver failure
3. Cause of patient’s liver disease is due to another condition, in the investigator’s opinion
4. Patient has severe anemia defined as hemoglobin of = 9 g/dL (result will be available after start of run-in period*)
5. Patient has experienced a gastrointestinal bleed within 6 months (24 weeks) prior to screening visit
6. Patient has moderate or severe renal impairment defined as creatinine clearance of = 30 mL/min (result will may not be available until after start of run-in period*), or patient has nephritis or nephrotic syndrome, in the opinion of the investigator
7. Patient has neurological disease that prevents swallowing of study medication (e.g. requires a nasogastric feeding tube) or requires intensive in-patient medical care
8. Patient is currently taking medication containing trientine for management of Wilson’s disease or has taken it within 4 months (16 weeks) of screening visit
9. Patient is currently receiving prescribed zinc therapy for management of Wilson’s disease or has taken it within 4 months (16 weeks) of screening visit
10. Patient is taking any of the following concomitant therapies: gold therapy, antimalarial therapy, cytotoxic drugs, oxyphenbutazone, phenyl butazone
11. Patient has a known intolerance, allergy or sensitivity to penicillamine (that is uncontrolled) or to TETA 4HCl, including any component of the study medication
12. For female patients of childbearing potential, planning a pregnancy during study period or currently nursing
13. For female patients of childbearing potential, unable or unwilling to use a reliable form of contraceptive throughout the study
14. Patient is currently participating in another therapeutic study, or has previously participated in a therapeutic study within 30 days of screening visit (or longer, if local requirements specify this)
15. Patient has any condition or in any situation which, in the investigator’s opinion, puts the patient at significant risk, could confound study results, or may interfere significantly with the patient’s participation in the study

*Samples for screening/enrolment labs can be taken within ± 7 days of visit. In the event that lab value is above the specified threshold, it can be repeated. If repeat value within specified range, patient can continue in the study, otherwise the patient will be a screen failure. Note: if it is not possible to obtain a repeat value prior to the Week 4 clinic visit, then the Week 4 value will serve as the repeat lab value(s).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of TETA 4HCl compared to penicillamine.<br>;Secondary Objective: The safety of TETA 4HCl compared to penicillamine will also be evaluated.;Primary end point(s): To evaluate the efficacy of TETA 4HCl compared to penicillamine:<br>The primary hypothesis is that the efficacy of TETA 4HCl, as assessed by serum NCC levels, is not inferior to the efficacy of penicillamine, at 36 weeks of treatment.<br>The secondary efficacy measures are:<br>- 24-hour urinary copper excretion<br>- CGIC score<br>Other efficacy measures are:<br>- Unified Wilson’s Disease Rating Scale (UWDRS), neurological scale<br>- Serum total copper and serum ceruloplasmin (used to derive non-ceruloplasmin bound copper).<br>Significance tests will be performed at the a = 0.05 significance level for two-tailed tests at a= 0.025 for one tailed test;Timepoint(s) of evaluation of this end point: Measured at Screening/Enrolment, Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The safety of TETA 4HCl compared to penicillamine will also be evaluated<br>Safety will be evaluated by assessing treatment emergent AEs (TEAEs), and other safety measures (vital signs, hematology, biochemistry, coagulation analysis, urinalysis, modified Nazer score, and urine pregnancy test). ;Timepoint(s) of evaluation of this end point: Measured at Screening, Weeks 4, 8, 12, 16, 20, 24, 28, 32 and 36