Results of the up-titration phase of the UNITED study, an open label, multicenter, prospective study to characterize the pharmacokinetics and pharmacodynamics of trientine dihydrochloride and to investigate the efficacy and safety in Wilson disease patients

I Mohr; A Czlonkowska; P Socha; A Poujois; A Ala; T Sandahl; S Bansal; E Couchonnal; M Praktiknjo; C Leemhuis; C Kruse; K H Weiss; A Dhawan

doi:10.1055/s-0045-1810640

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Z Gastroenterol 2025; 63(08): e369-e370
DOI: 10.1055/s-0045-1810640

Abstracts | DGVS/DGAV

Freie Vorträge

Results of the up-titration phase of the UNITED study, an open label, multicenter, prospective study to characterize the pharmacokinetics and pharmacodynamics of trientine dihydrochloride and to investigate the efficacy and safety in Wilson disease patients

Authors

I Mohr

¹University Hospital Heidelberg, Department of Gastroenterology and Hepatology, Heidelberg, Deutschland
A Czlonkowska

²Institute of Psychiatry and Neurology, Department of Neurology, Warsaw, Polen
P Socha

³The Children's Memorial Health Institute, Departments of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Warsaw, Polen
A Poujois

⁴Hopital Fondation Adolphe de Rothschild, Département de Neurologie, Centre de Reference de la Maladie de Wilson,, Paris, Frankreich
A Ala

⁵King's College Hospital NHS Foundation Trust, Institute of Liver Studies, London, Vereinigtes Königreich
T Sandahl

⁶Aarhus University Hospital, Dept. of Hepatology and Gastroenterology,, Aarhus, Dänemark
S Bansal

⁷King's College Hospital, Department of Pediatrics and Pediatric Liver GI and Nutrition Center and Mowat Labs, London, Vereinigtes Königreich
E Couchonnal

⁸Hospices Civils de Lyon- Hôpital Femme Mère Enfant, Hépatologie, Gastroentérologie et Nutrition pédiatrique, Centre de Référence de la maladie de Wilson, Pinel, Frankreich
M Praktiknjo

⁹University Hospital Münster, Department of Internal Medicine B, Münster, Deutschland
C Leemhuis

¹⁰Univar Solutions B.V., Rotterdam, Niederlande
C Kruse

¹⁰Univar Solutions B.V., Rotterdam, Niederlande
K H Weiss

¹¹Salemkrankenhaus, Innere Medizin, Heidelberg, Deutschland
A Dhawan

⁷King's College Hospital, Department of Pediatrics and Pediatric Liver GI and Nutrition Center and Mowat Labs, London, Vereinigtes Königreich

Abstract

Volltext

Background: Trientine dihydrochloride (TETA-2HCl) has been used for the treatment of Wilson Disease for almost 40 years. Although its ability to chelate metal ions has been demonstrated in both non-clinical and clinical settings, no dedicated dose-response studies are available.

Aim: The UNITED study aims to investigate a possible pharmacokinetic (PK) – pharmacodynamic (PD) relationship of TETA-2HCl and further evaluate its efficacy and safety. The results of the PKPD sub-study with data obtained during the up-titration phase, are presented here.

Method: This study is designed as an open label, multicenter prospective study containing PK, PD, efficacy and safety assessments to evaluate a potential dose-exposure-response relationship as well as to determine the long-term efficacy and safety of TETA-2HCl (Cufence). The PKPD sub-study includes data up to Visit 4 (i.e. the Up-Titration Phase). At baseline, treatment was initiated, and patients were up-titrated per visit [Visit 2 (3 mg/kg/day), Visit 3 (8 mg/kg/day), Visit 4 (13 mg/kg/day)]. Plasma PK as well as serum copper (Cu), serum ceruloplasmin (Cp), 24-hour urinary copper excretion (24-hr UCE) levels and Non-Ceruloplasmin Bound Copper (NCC, calucated and directly) were measured at each visit. Furthermore, neurological, hepatic and psychiatric assessments were applied.

Results: A total of 51 patients were enrolled in the UNITED study and data was collected at 9 sites in Germany, France, Poland, Denmark and the UK. The mean (SD) age of the patients was 34.9 (17.29) years, and 32 patients [62.75%] were male. The majority presented with predominantly hepatic features (n=34 [66.67%]). The highest mean plasma concentrations were observed at 1h post administration of trientine. No clear trend towards an influence of predominant symptomatic presentation or age of the patients on mean plasma concentration could be determined. When looking at Cu, Cp, 24-hr UCE and NCC following TETA-2HCl administration a trend was observed when comparing the different age groups. Also, a clear increase of 24-hr UCE could be observed for all patient groups. The liver endpoints did not show any change and no serious TEAEs or deaths were observed during the up-titration phase.

Conclusion: The results of this PKPD sub-study show that up-titration of TETA-2HCl in multiple bodyweight dependent steps is generally safe and well tolerated, and that there are possible indications for a relationship between the PK, PD and age.

Abstracts

Präsentiert in der Sitzung: Neue Therapieoptionen bei Speicherkrankheiten der Leber – von häufig bis ultraselten

Donnerstag, 18. September 2025, 11:30 – 13:00, Saal 4