Once-Daily Trientine Enters Phase 3 Trial for First-Line Treatment in Wilson Disease

Orphalan has initiated TRADITiONAL (NCT07465718), a new global phase 3 trial comparing an investigational once-daily formulation of trientine tetrahydrochloride with D-penicillamine as first-line treatment for Wilson disease. The 48-week study will assess efficacy, safety, tolerability, and treatment satisfaction in patients aged 8 years or older.¹

“Successful management of Wilson disease requires lifelong therapy, and current treatment regimens can be complex and burdensome for many patients, posing significant challenges with adherence,” Omar Kamlin, MD, chief medical officer at Orphalan, said in a statement.¹ "The initiation of the global TRADITiONAL Study in the USA reflects Orphalan's commitment in addressing the unmet needs of Wilson disease patients by investigating a therapeutic approach which may simplify the treatment burden."

TRADITiONAL is a randomized, parallel-group, open-label, multicenter study enrolling symptomatic and asymptomatic patients with Wilson disease. Eligible participants must be treatment-naive or naive to chelator therapy. Symptomatic patients who have received zinc salts for no more than 28 days may also qualify. Following an approximately 4-week screening period, participants will be randomly assigned to 48 weeks of trientine tetrahydrochloride or D-penicillamine.²

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The trial is intended to determine whether a once-daily chelation regimen can provide an alternative to D-penicillamine while potentially reducing treatment burden. Patient-reported treatment satisfaction will be assessed alongside clinical efficacy, safety, and tolerability. Initial US sites include the University of Colorado Anschutz School of Medicine, Yale University School of Medicine, and the University of Michigan Medical Center. Enrollment is expected to expand to China, Pakistan, and Saudi Arabia.

For context, Wilson disease is a rare autosomal recessive disorder caused by pathogenic variants in ATP7B, which impair copper excretion. Copper subsequently accumulates in tissues, particularly the liver and brain, and may produce hepatic, neurologic, and psychiatric manifestations. Without effective lifelong treatment, the disease can be fatal.

Copper-chelating therapy promotes removal of excess copper, whereas zinc salts reduce intestinal copper absorption. D-penicillamine is an established chelator used in Wilson disease, but the need for lifelong administration makes tolerability and adherence clinically consequential. The comparison with D-penicillamine is clinically relevant because the study is focused on initial therapy rather than switching patients who are already stable on another regimen.

REFERENCES
1. Orphalan initiates global phase 3 TRADITiONAL study of investigational once-daily trientine therapy in Wilson disease. News release. Orphalan. September 7, 2026. Accessed September 9, 2026. https://www.orphalan.com/orphalan-initiates-global-phase-3-traditional-study-of-investigational-once-daily-trientine-therapy-in-wilson-disease/
2. ClinicalTrials.gov. Study NCT07465718: TRADITiONAL study of trientine tetrahydrochloride in Wilson disease. US National Library of Medicine.