We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02763215
Recruitment Status : Completed
First Posted : May 5, 2016
Results First Posted : October 26, 2020
Last Update Posted : December 1, 2020
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:

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.


Condition or disease Intervention/treatment
Wilson Disease Drug: Standard of Care Medications

Layout table for study information
Study Type : Observational
Actual Enrollment : 64 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Multi-Center Study for the Assessment of Copper Parameters in Wilson Disease Subjects on Standard of Care Treatment
Actual Study Start Date : May 19, 2016
Actual Primary Completion Date : January 21, 2019
Actual Study Completion Date : January 21, 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline through Month 6 ]
    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.


Secondary Outcome Measures :
  1. Percentage Of Participants Who Achieved Or Maintained Normalized Concentrations Of NCC Or Reached A Reduction Of ≥ 25% In NCC Through Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  2. Change From Baseline In NCC Concentrations At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  3. Time To Normalization Of NCC If Above The Reference Range At The Time Of Enrollment [ Time Frame: Baseline, up to 24 months ]
    The time to normalization of NCC was measured by Kaplan-Meier analysis.

  4. Change From Baseline In Exchangeable Copper At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  5. Change From Baseline In Copper Plasma Ultrafiltrate At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  6. Change From Baseline In Plasma Total Copper Used To Calculate NCC At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  7. Change From Baseline In Serum Total Ceruloplasmin (Nephelometry) Used To Calculate NCC At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  8. Change From Baseline In 24-Hour Urinary Copper At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  9. Change From Baseline In Plasma Total Molybdenum At Month 6 And Month 24 [ Time Frame: Baseline, Month 6, Month 24 ]
    The plasma total molybdenum was measured over time and is reported in ng/mL.

  10. Change From Baseline In Molybdenum Plasma Ultrafiltrate At Month 6 And Month 24 [ Time Frame: Baseline, Month 6, Month 24 ]
    The molybdenum plasma ultrafiltrate was measured over time and is reported as ng/mL.

  11. Change From Baseline In 24-Hour Urinary Molybdenum At Month 6 And Month 24 [ Time Frame: Baseline, Month 6, Month 24 ]
    Evaluation of 24-hour urinary molybdenum over time is reported as μg/day.

  12. Change From Baseline In Hepatic Laboratory Measures For Alanine Aminotransferase (ALT) At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  13. Change From Baseline In Hepatic Laboratory Measures For Aspartate Aminotransferase (AST) At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  14. Change From Baseline In Hepatic Laboratory Measures For Bilirubin At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  15. Change From Baseline In Hepatic Laboratory Measures For International Normalized Ratio (INR) At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    The INR was measured over time. Last Assessment was the last available post-baseline result for each participant (ranging from 1 to 24 months).

  16. Change From Baseline In Clinical Global Impression (CGI) Scale Item 1 (Severity Of Illness) At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).

  17. CGI Scale Item 2 (Global Improvement) At Month 6, Month 24, And Last Assessment [ Time Frame: Baseline through Last Assessment (ranging from 1 to 24 months) ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02763215


Locations
Layout table for location information
United States, Connecticut
Clinical Trial Site
New Haven, Connecticut, United States, 06504
United States, Illinois
Clinical Trial Site
Chicago, Illinois, United States, 60611
United States, Michigan
Clinical Trial Site
Ann Arbor, Michigan, United States, 48109
United States, Tennessee
Clinical Trial Site
Nashville, Tennessee, United States, 37240
United States, Washington
Clinical Trial Site
Seattle, Washington, United States, 98105
Austria
Clinical Trial Site
Vienna, Austria, 1090
Germany
Clinical Trial Site
Heidelberg, Germany, 69120
Poland
Clinical Trial Site
Warszawa, Poland, 02-957
United Kingdom
Clinical Trial Site
Birmingham, United Kingdom, B15 2GW
Clinical Trial Site
Guildford, United Kingdom, GU2 7XX
Sponsors and Collaborators
Alexion Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Alexion Pharmaceuticals, Inc. Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] September 21, 2016
Statistical Analysis Plan  [PDF] May 17, 2019

Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02763215    
Other Study ID Numbers: WTX101-203
First Posted: May 5, 2016    Key Record Dates
Results First Posted: October 26, 2020
Last Update Posted: December 1, 2020
Last Verified: November 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatolenticular Degeneration
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
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Metabolic Diseases