Trientine Tetrahydrochloride Administered Once a Day for the First Line Treatment of Wilson's Disease Patients.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат TETA 4HCl formulation
  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.
• Препарат D-Penicillamine
  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.

Первичные конечные точки

• Absolute value of serum NCC at Week 48 assessed using the NCC-speciation assay (serum NCC-Sp) [Срок оценки: Week 48]

Вторичные конечные точки (5)

• Serum NCC-Sp [Срок оценки: Week 48]
• 24-hour UCE [Срок оценки: Week 48]
• Investigator's assessment of signs and symptoms [Срок оценки: Week 48]
• Clinical Global Impression of Change [Срок оценки: Week 48]
• Clinical stability [Срок оценки: Week 48]

Критерии участия

Критерии включения

• 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 4. 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.
• Willing to comply with low copper diet for the duration of the study.
• Participant requires treatment for WD, in the opinion of the Investigator.
• Participant is able to take the study medication as prescribed, in the opinion of the Investigator.

Критерии исключения

• 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 12.
• 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.
• Alanine aminotransferase greater than 5 times upper limit of normal (ULN).
• Severe pulmonary disease requiring home nebulization and/or home oxygen therapy.
• Clinically significant gastrointestinal bleed within past 6-months.
• Neurological disease requiring either nasogastric feeding or intensive inpatient medical care.
• Active or history of seizures requiring anti-epileptics within 6 months prior to informed consent.
• Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus or seropositivity for human immunodeficiency virus (HIV).
• Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the collection or interpretation of the study results.
• Female participants of childbearing potential, currently pregnant, currently nursing, or planning a pregnancy during study period.
• Female participants of childbearing potential, unable or unwilling to use a reliable form of contraceptive throughout the study.
• Male participants, unable or unwilling to use a reliable form of contraceptive throughout the study.
• Participant is not willing to comply with the prohibited medication requirements for the study.
• In the opinion of the Investigator, the participant is likely to be non-compliant or uncooperative for the required study visits or study assessments, or has any disease, disability, illness or abnormal laboratory values that could compromise patient safety or interfere with the collection or interpretation of study results.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of Colorado Anschutz School of Medicine — Denver
• Yale University School of Medicine — New Haven
• University of Michigan Medical Centre — Ann Arbor

Китай · 3 центра

• Beijing YouAn Hospital, Capital Medical University — Пекин
• Beijing Friendship Hospital,Capital Medical University — Пекин
• The Second Affiliated Hospital Zhejiang University School of Medicine — Ханчжоу

Пакистан · 3 центра

• PIMS Hospital — Islamabad
• Shifa International Hospital — Islamabad
• Children's Hospital & Institute of Child Health — Lahore

Саудовская Аравия · 1 центр

• King Faisal Specialist Hospital and Research Center — Riyadh

Идентификаторы

NCT: NCT07465718 · ORPH-131-017

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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