The Assessment of Copper Parameters in Wilson Disease Participants on Standard of Care Treatment

Multi-Center Study for the Assessment of Copper Parameters in Wilson Disease Subjects on Standard of Care Treatment

This was a 24-month study to assess copper parameters in participants with Wilson disease (WD) treated with standard of care (SoC) medications.

After providing informed consent, participants meeting all inclusion and no exclusion criteria were enrolled into the study as outpatients. The participants' routine clinic visits were scheduled according to the standard clinical practice at the study center and at the discretion of the treating physician at approximate 6-month intervals.

At the time of enrollment, participants were receiving SoC medications for the treatment of WD, which could include penicillamine, trientine, zinc, or a combination of a copper chelator and zinc. If treatment was interrupted or stopped during the course of the study, participants continued in the study and biological samples and clinical data were continued to be collected for the full 24-month study period. Dosing with SoC agents was individualized and managed by the treating physician at the study center according to standard clinical practice at the site.

Study Overview

• Status: Completed
• Conditions: Wilson Disease
• Intervention / Treatment: Drug: Standard of Care Medications

• Study Type: Observational
• Enrollment (Actual): 64

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Clinical Trial Site
• Germany
  • Heidelberg, Germany, 69120
    • Clinical Trial Site
• Poland
  • Warszawa, Poland, 02-957
    • Clinical Trial Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Clinical Trial Site
  • Guildford, United Kingdom, GU2 7XX
    • Clinical Trial Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Clinical Trial Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Clinical Trial Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Wilson disease participants receiving SoC medications for the treatment of WD. Standard of care medications could include penicillamine, trientine, zinc, or a combination of a copper chelator and zinc.

Description

Inclusion Criteria:

• Willing and able to give informed consent for participation in the study.
• Male or female participants, aged 18 years or older as of signing the informed consent form.
• Receiving SoC medications (penicillamine, trientine, zinc, or copper chelators with zinc) for the treatment of WD at the time of enrollment and for no more than 60 months prior to enrollment.
• Able to understand and willing to comply with study procedures and requirements, as judged by the Investigator.
• Established diagnosis of WD.
• Adequate venous access to allow for collection of blood samples.

Exclusion Criteria:

• Major systemic disease or other illness that would, in the opinion of the Investigator, compromise participant safety or interfere with the collection or interpretation of study results.
• In the opinion of the Investigator, the participant was likely to be non-compliant or uncooperative during the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Total	Drug: Standard of Care Medications; Standard of care medications could include penicillamine, trientine, zinc, or a combination of a copper chelator and zinc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Of Participants Who Achieved Or Maintained Normalized Concentrations Of Non-ceruloplasmin-bound Copper (NCC) Or Reached A Reduction Of ≥ 25% In NCC During 6 Months Of Treatment	To achieve a normalized NCC concentration, participants must have had 2 consecutive measures within (or below) the normal concentration range (0.8 to 2.3 micromolar [μM]). Two consecutive measurements required that the measurements occurred on separate dates and were assigned to 2 different visits. Non-ceruloplasmin-bound copper was calculated by subtracting the amount of copper bound to the ceruloplasmin from the total plasma copper concentration.	Baseline through Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Of Participants Who Achieved Or Maintained Normalized Concentrations Of NCC Or Reached A Reduction Of ≥ 25% In NCC Through Last Assessment	To achieve a normalized NCC concentration, participants must have 2 consecutive measures within (or below) the normal range (0.8 to 2.3 μM). Two consecutive measurements required that the measurements occurred on separate dates and were assigned to 2 different visits. Non-ceruloplasmin-bound copper was calculated by subtracting the amount of copper bound to the ceruloplasmin from the total plasma copper concentration. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In NCC Concentrations At Month 6, Month 24, And Last Assessment	Evaluation of NCC concentrations over time are reported as micromoles/liter (μmol/L). Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Time To Normalization Of NCC If Above The Reference Range At The Time Of Enrollment	The time to normalization of NCC was measured by Kaplan-Meier analysis.	Baseline, up to 24 months
Change From Baseline In Exchangeable Copper At Month 6, Month 24, And Last Assessment	The change in exchangeable copper was evaluated over time and is reported as nanograms/milliliter (ng/mL). Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Copper Plasma Ultrafiltrate At Month 6, Month 24, And Last Assessment	Change in copper plasma ultrafiltrate was measured over time and is reported as ng/mL. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Plasma Total Copper Used To Calculate NCC At Month 6, Month 24, And Last Assessment	Plasma total copper was measured over time and is reported as ng/mL. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Serum Total Ceruloplasmin (Nephelometry) Used To Calculate NCC At Month 6, Month 24, And Last Assessment	The total serum (nephelometry) was measured over time and is reported as milligrams (mg)/L. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In 24-Hour Urinary Copper At Month 6, Month 24, And Last Assessment	Evaluation of 24-hour urinary copper over time is reported as micrograms (μg)/day. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Plasma Total Molybdenum At Month 6 And Month 24	The plasma total molybdenum was measured over time and is reported in ng/mL.	Baseline, Month 6, Month 24
Change From Baseline In Molybdenum Plasma Ultrafiltrate At Month 6 And Month 24	The molybdenum plasma ultrafiltrate was measured over time and is reported as ng/mL.	Baseline, Month 6, Month 24
Change From Baseline In 24-Hour Urinary Molybdenum At Month 6 And Month 24	Evaluation of 24-hour urinary molybdenum over time is reported as μg/day.	Baseline, Month 6, Month 24
Change From Baseline In Hepatic Laboratory Measures For Alanine Aminotransferase (ALT) At Month 6, Month 24, And Last Assessment	The ALT levels were measured over time and are reported as units (U)/L. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Hepatic Laboratory Measures For Aspartate Aminotransferase (AST) At Month 6, Month 24, And Last Assessment	The AST levels were measured over time and are reported as U/L. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Hepatic Laboratory Measures For Bilirubin At Month 6, Month 24, And Last Assessment	Bilirubin was measured over time and is reported as μmol/L. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Hepatic Laboratory Measures For International Normalized Ratio (INR) At Month 6, Month 24, And Last Assessment	The INR was measured over time. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
Change From Baseline In Clinical Global Impression (CGI) Scale Item 1 (Severity Of Illness) At Month 6, Month 24, And Last Assessment	The CGI scale item 1 (severity of illness) rating scale is a commonly used measure of symptom severity, treatment response, and the efficacy of treatments in treatment studies of participants with mental disorders. It uses the Clinical Global Impression - Severity Scale (CGI-S), a 7-point scale that requires the Investigator to rate the severity of the participant's illness at the time of assessment, relative to the Investigator's past experience with participants who had the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at the time of rating as: 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. A decrease in score indicates improvement in disease severity. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)
CGI Scale Item 2 (Global Improvement) At Month 6, Month 24, And Last Assessment	The CGI scale item 2 (global improvement) is a rating scale commonly used measure of symptom severity, treatment response, and the efficacy of treatments in treatment studies of participants with mental disorders. It uses the Clinical Global Impression - Improvement Scale (CGI-I), a 7-point scale that requires the Investigator to assess how much the participant's illness has improved or worsened relative to the Baseline state at the beginning of the study and rate as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A decrease in score indicates improvement in disease severity. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).	Baseline through Last Assessment (ranging from 1 to 24 months)

Collaborators and Investigators

• Sponsor: Alexion
• Investigators: Study Director: Alexion Pharmaceuticals, Inc., Alexion

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2016
• Primary Completion (Actual): January 21, 2019
• Study Completion (Actual): January 21, 2019

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Metal Metabolism, Inborn Errors; Hepatolenticular Degeneration
• Other Study ID Numbers: WTX101-203