The goal of this clinical trial is to learn if a new trientine tetrahydrochloride (TETA 4HCl) formulation administered once a day compared to d-Penicillamine (DPA) as a first line treatment for people living with Wilson's disease (WD) is effective and safe. The study is enrolling children aged 8 years and older weighing at least 55 lb (25 kg) and adults with a recent diagnosis of WD. People recently diagnosed with WD, may be eligible for the study if they have either not started copper chelating treatment (such as DPA or trientine) or have been taking zinc salts for less than 28 days. Participants will be randomly allocated (like tossing a coin) to receive either DPA or TETA 4HCL for 48 weeks. During this time period participants will have up to 12 visits for health checks and assessments including blood and urine testing. In addition, at some visits participants may be asked to complete questionnaires on treatment satisfaction, and overall well-being.
Wilson's disease (WD) is a rare, autosomal recessive genetic disorder of copper metabolism leading to progressive copper accumulation primarily in the liver and brain. Chelators are drugs that bind and remove copper from the body in the urine. d-Penicillamine (DPA) is currently the only approved first line chelator for the treatment of WD with trientine, an alternative copper chelator, only indicated for second line use. DPA is associated with numerous side effects which may lead to drug discontinuation in approximately 30% of people living with WD. Trientine is used following intolerance to DPA. All current WD therapies have to be taken multiple times a day. This can be challenging for people living with WD who have to take treatment every day and lifelong. A new formulation of trientine tetrahydrochloride (TETA 4HCl) has been developed to be administered once a day. Recently diagnosed consenting people with WD will enter a 28-day screening period (as required for confirmation of WD diagnosis, detailed neurological evaluation, and results of tests for eligibility) and a 48-week follow-up post-randomization. Symptomatic and asymptomatic WD patients 8 years of age and older with a body weight of at least 25 kg who are either naïve to all WD therapies (treatment-naïve) or naïve to chelator WD therapy (chelator-naïve) will be enrolled. Participants will receive treatment with either DPA or TETA 4HCl for the 48 week post-randomization period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
The new formulation of TETA 4HCl will be administered once a day. Each film-coated tablet is scored to enable halving, if required. Randomized participants are planned to receive TETA 4HCl for the 48-week post-randomization period.
Standard of care DPA is to be used, per the sites and treating physician's usual practice. To be administered in accordance with the product labelling and/or the institutions treatment practice guidelines. Randomised participants are planned to receive DPA for the 48-week post-randomization period.
University of Colorado Anschutz School of Medicine
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
University of Michigan Medical Centre
Ann Arbor, Michigan, United States
Beijing YouAn Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Beijing Friendship Hospital,Capital Medical University
Beijing, Beijing Municipality, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhengjiang Province, China
PIMS Hospital
Islamabad, Pakistan
Shifa International Hospital
Islamabad, Pakistan
Children's Hospital & Institute of Child Health
Lahore, Pakistan
King Faisal Specialist Hospital and Research Center
Riyadh, Saudi Arabia
Absolute value of serum NCC at Week 48 assessed using the NCC-speciation assay (serum NCC-Sp)
Time frame: Week 48
Serum NCC-Sp
Change from Baseline, within specified thresholds \[\>200, ≤ 200, ≤ 150, ≤ 100, ≤ 80, ≤ 50 μg/L and 50 to 80 μg/L\]
Time frame: Week 48
24-hour UCE
Absolute value, change from Baseline, within specified thresholds \[\< 100, \<200, \> 500, 150 to 500, and 200 to 500 μg/24h\]
Time frame: Week 48
Investigator's assessment of signs and symptoms
Assessment of of the signs and symptoms of WD using GAS for WD, comprising a 4-item Global Disability (Tier 1) and 10-item Neurological Assessment (Tier 2). Total score, Tier 1 score, Tier 2 score, each item score.
Time frame: Week 48
Clinical Global Impression of Change
Investigator rating of change in the patients WD relating to the prior clinic visit on a 7-point scale by responding to the following statement "Please rate the change in the overall severity of the patients Wilson's disease compared to the previous clinic visit".
Time frame: Week 48
Clinical stability
As assessed by Independent Adjudication Committee, including final determination of the endpoint of clinical stability (yes/no), including successful de-coppering (as applicable).
Time frame: Week 48
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