Trientine Tetrahydrochloride Administered Once a Day for the First Line Treatment of Wilson's Disease Patients.
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Orphalan
- Enrollment
- 38
- Locations
- 3
- Primary Endpoint
- Absolute value of serum NCC at Week 48 assessed using the NCC-speciation assay (serum NCC-Sp)
Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 8 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant is aged 8 years or older and is willing and able to give informed consent for participation in the study, or by a parent/legally authorized representative (LAR) and assent obtained (in accordance with local regulations) for any participant less than the age of majority (e.g. less than 18 years of age, depending on local requirements).
- •Participant has a body weight of at least 25 kg at screening.
- •Participant has a diagnosis of WD, as defined by a Leipzig score of greater than or equal to
- •Note that historical test results can be used for the diagnosis.
- •Participant has either:
- •Received no prior prescribed therapy \[a\] for the treatment of WD (treatment-naïve), or
- •Received no prescribed chelator therapy \[a\] for the treatment of WD (chelator-naïve); zinc salts are permitted for no more than 28 days prior to the start of screening assessments, and these participants must be symptomatic.
- •\[a\] prescribed therapy for WD refers to the authorized chelator treatments of trientine (TETA 2HCl or TETA 4HCl) and DPA, or zinc salts.
- •Able and willing to comply with study procedures and requirements, as described in the informed consent.
- •Adequate venous access to allow collection of required blood samples.
Exclusion Criteria
- •Any known contraindications for treatment with DPA.
- •Any known contraindications for treatment with TETA 4HCl.
- •Unable to swallow tablets/capsules independently or considered high risk for aspiration, in the opinion of the Investigator
- •Acute liver failure (ALF) or at high risk of ALF, in the opinion of the Investigator.
- •Decompensated hepatic cirrhosis, in the opinion of the Investigator.
- •Participants 12 years or older at screening, Model for End stage Liver Disease (MELD) score of greater than or equal to
- •Participants 8 to 11 years at screening, Model for Pediatric End stage Liver Disease (PELD) of greater than or equal to 10
- •Hemoglobin of less than or equal to 9 g/dL.
- •Estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m²
- •Nephritis or nephrotic syndrome, in the opinion of the Investigator.
Arms & Interventions
TETA 4HCl formulation
Participants are planned to receive TETA 4HCl for the 48-week post-randomization period.
Intervention: TETA 4HCl formulation (Drug)
Standard of care d-Penicillamine (DPA)
Participants are planned to receive DPA for the 48-week post-randomization period.
Intervention: D-Penicillamine (Drug)
Outcomes
Primary Outcomes
Absolute value of serum NCC at Week 48 assessed using the NCC-speciation assay (serum NCC-Sp)
Time Frame: Week 48
Secondary Outcomes
- Serum NCC-Sp(Week 48)
- 24-hour UCE(Week 48)
- Investigator's assessment of signs and symptoms(Week 48)
- Clinical Global Impression of Change(Week 48)
- Clinical stability(Week 48)