Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease

NCT03539952 | Completed Phase 3 Results FDA Drug

• 1 other identifier: GMPO-131-002
• Study Type: interventional
• Target: 77
• Locations: 9 countries
• Sites: 15

Brief Summary

This is a multicenter, randomized, open-label study with an active standard-of-care comparator (penicillamine)

Conditions

Wilson Disease

Outcome Measures

Primary Outcomes (1)

• Serum NCC Concentration

  The primary outcome of efficacy was serum NCC by speciation assay (μg/L), with comparative analysis of mean difference between the two groups 24 weeks after randomization. The non-inferiority margin was set at -50 μg/L.

  Week 36

Secondary Outcomes (2)

• 24-hour Urinary Copper Excretion (UCE)

  Week 36

• Clinical Global Impression of Change (CGIC) Rating Scale

  Week 36

Study Arms (2)

Penicillamine arm

ACTIVE COMPARATOR

Patients randomized to penicillamine during the postrandomisation and 1st extension period

Drug: Penicillamine (D1-W12); Drug: Penicillamine (W12-W60); Drug: TETA 4HCL (60-<W108)

Trientine arm

EXPERIMENTAL

Patients randomized to TETA 4HCl during the postrandomisation and 1st extension period

Drug: Penicillamine (D1-W12); Drug: TETA 4HCL (W12-60); Drug: TETA 4HCL (60-<W108)

Interventions

Penicillamine (D1-W12) DRUG

Penicillamine during baseline period (D1-W12)

Also known as: D-penicillamine

Penicillamine arm; Trientine arm

TETA 4HCL (W12-60) DRUG

TETA 4HCL during post randomisation and 1st extension period (W12-W60)

Also known as: trientine tetrahydrochloride

Trientine arm

Penicillamine (W12-W60) DRUG

Penicillamine during rondomisation and 1st extension period period (W12-W60)

Also known as: D-Penicillamine

Penicillamine arm

TETA 4HCL (60-<W108) DRUG

TETA 4HCL during 2nd extension period (W60-\<W108)

Also known as: trientine tetrahydrochloride

Penicillamine arm; Trientine arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is able to provide, and has provided, written informed consent
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable, including: For US sites: Authorization for Use and Release of Health Research Study Information and for EU sites: Data Protection Consent
• Male or female, aged ≥ 18 and ≤ 75 years of age at time of consent
• Patient has a diagnosis of Wilson's disease, as defined by a prior or current Leipzig score of ≥ 4
• Patient's Wilson's disease is clinically stable, in the opinion of the investigator, and being treated with penicillamine for at least 1 year (52 weeks) prior to the screening/enrolment visit
• Patient is on a stable dose and regimen of penicillamine for at least 4 months (16 weeks) prior to the screening/enrolment visit (other prescribed treatments for Wilson's disease not permitted during this study)
• No anticipated need that patient will require additional pharmacological therapies other than study medication, including prescribed zinc therapy, for the management of copper levels during the study
• Patient must be willing to maintain stable diet throughout the study, and avoid foods with high copper content, including the Penicillamine Baseline Period
• Patient considered suitable to receive therapy with both TETA 4HCl and penicillamine administered twice a day
• Negative central laboratory tests for HIV and viral hepatitis (results will be available after start of run-in period)
• For female patients of childbearing potential, negative urine pregnancy test (at screening/enrolment visit and prior to randomization)
• For females of childbearing potential, use of a reliable form of contraceptive
• Patient is considered as able to complete study requirements and attend the study visits, in the opinion of the investigator
• Patient is adequately controlled and tolerating penicillamine therapy as defined by fulfilment of all of the following: a. Serum non-ceruloplasmin bound copper (NCC) level between ≥ 25 and ≤ 150 μg/L\* b. 24-hour urinary copper excretion of between ≥ 100 and ≤ 900 μg/24 hours\* c. Alanine transaminase (ALT) \< 2 times upper limit of normal\* d. No other laboratory or clinical findings that would prevent continuation of maintenance therapy, in the opinion of the investigator
• \* Based on results from screening/enrolment visit samples for which can be taken within ± 7 days of visit. Result should be within the assay limits of quantification for the sample. The ranges in μmol of copper are 0.40 to 2.38 μmol/L for NCC and 1.59 to 14.29 for 24-hour urinary copper excretion (using division by 63 of value in μg per Walshe, 2011). In the event that one or more of the above lab values fall outside the specified range, it can be repeated, including at the Week 4 and Week 8 visits.

You may not qualify if:

• Patient is in 'de-coppering' phase of treatment for Wilson's disease, in the opinion of the investigator
• Patient evidence of uncontrolled liver disease, including but not limited to:
• Modified Nazer score of \> 4 (result may not be available until after start of run in period since based on lab results\*)
• decompensated cirrhosis
• acute hemolytic anemia
• acute hepatitis
• hepatic malignancy
• evidence of acute liver failure
• Cause of patient's liver disease is due to another condition, in the investigator's opinion
• Patient has severe anemia defined as hemoglobin of ≤ 9 g/dL (result will be available after start of run-in period\*)
• Patient has experienced a gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrolment visit
• Patient has renal impairment defined as creatinine clearance of ≤ 30 mL/min (result may not be available until after start of run-in period\*), or patient has nephritis or nephrotic syndrome, in the opinion of the investigator
• Patient has neurological disease that prevents swallowing of study medication (e.g., requires a nasogastric feeding tube) or requires intensive in-patient medical care
• Patient is currently taking medication containing trientine for management of Wilson's disease or has taken it within 4 months (16 weeks) of screening/enrolment visit
• Patient is currently receiving prescribed zinc therapy for management of Wilson's disease or has taken it within 4 months (16 weeks) of screening/enrolment visit

Sponsors & Collaborators

• Orphalan: lead

Study Sites (15)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

KU Leuven, Department of Clinical and Experimental Medicine

Leuven, Belgium

Location

Hospital Nossa Senhora das Graças (HNSG)

Curitiba, Brazil

Location

Nucleo de Pesquisa e Desenvolvimento de Medicamentos - Universidade Federal do Ceará - Rodolfo Teófilo

Fortaleza, 60430-275, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, Brazil

Location

Hepato-gastroenterologisk afd

Aarhus, Denmark

Location

Hospital mother children

Bron, 69677, France

Location

Centre National de Référence Wilson, Hôpital Lariboisière

Paris, 75475, France

Location

Innere Medizin

Heidelberg, 69120, Germany

Location

Poliklinik Hepatologie/Transplantationsambulanz

Munich, 81377, Germany

Location

A.O. San Paolo Milano

Milan, 20142, Italy

Location

DiSCOG Gastroenterology Unit

Padua, 35128, Italy

Location

Institute of Psychiatry and Neurology

Warsaw, 02 957, Poland

Location

University of Surrey, Department of Clinical and Experimental Medicine

Guildford, Surrey, GU2 7XH, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (2)

• Schilsky ML, Czlonkowska A, Zuin M, Cassiman D, Twardowschy C, Poujois A, Gondim FAA, Denk G, Cury RG, Ott P, Moore J, Ala A, D'Inca R, Couchonnal-Bedoya E, D'Hollander K, Dubois N, Kamlin COF, Weiss KH; CHELATE trial investigators. Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2022 Dec;7(12):1092-1102. doi: 10.1016/S2468-1253(22)00270-9. Epub 2022 Sep 30.

  PMID: 36183738 RESULT

• Ott P, Sandahl T, Ala A, Cassiman D, Couchonnal-Bedoya E, Cury RG, Czlonkowska A, Denk G, D'Inca R, de Assis Aquino Gondim F, Moore J, Poujois A, Twardowschy CA, Weiss KH, Zuin M, Kamlin COF, Schilsky ML. Non-ceruloplasmin copper and urinary copper in clinically stable Wilson disease: Alignment with recommended targets. JHEP Rep. 2024 May 6;6(8):101115. doi: 10.1016/j.jhepr.2024.101115. eCollection 2024 Aug.

  PMID: 39139457 DERIVED

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

Penicillamine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Frank Verheggen - Head Clinical Operations
• Organization: Orphalan SA

frank.verheggen@orphalan.com

+31625241264

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 30, 2018
• Study Start: September 3, 2018
• Primary Completion: August 19, 2020
• Study Completion: January 18, 2022
• Last Updated: July 2, 2025
• Results First Posted: April 20, 2023

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); DE (2); IT (2); BE (1); BR (3); US (1); DK (1); GB (2); FR (2)