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Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients

Primary Purpose

Wilson Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALXN1840
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wilson Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator.
  • Newly established diagnosis of WD by Leipzig-Score ≥ 4 documented by testing as outlined in 2012 European Association for the Study of the Liver Wilson Disease Clinical Practice Guidelines.
  • NCC levels within or above the normal reference range (0.8 to 2.3 micromole).
  • Willing to undergo 48 hour washout from current WD treatment

Exclusion Criteria:

  • Treatment for greater than 24 months for WD with chelation therapy (for example, penicillamine, trientine hydrochloride) or zinc therapy.
  • Decompensated hepatic cirrhosis.
  • Model for End-Stage Liver Disease score > 11.
  • Modified Nazer score > 6.
  • Gastrointestinal bleed within past 6 months.
  • Alanine aminotransferase > 5 x upper limit of normal.
  • Marked neurological disease requiring either nasogastric feeding or intensive in-patient medical care.
  • Severe anemia with a hemoglobin < 9 grams/deciliter.

Sites / Locations

  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALXN1840

Arm Description

Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligram (mg) per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks. Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range. ALXN1840 could have been received for up to 36 months in the Extension Period.

Outcomes

Primary Outcome Measures

Percentage Of Participants With Normalized Concentrations Of NCC
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole [μmol]l/liter [L]]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.

Secondary Outcome Measures

Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24
The change from Baseline in NCC adjusted for Mo plasma concentration over 24 weeks were analyzed and descriptive statistics are reported. Change from Baseline = (Week 24 NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% confidence intervals (CIs) were calculated using a restricted maximum likelihood (REML)-based mixed model for repeated measures (MMRM) with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC
For time to normalization of NCC adjusted for Mo plasma concentration, a Kaplan-Meier approach was used where participants not normalized were censored at the latest observed time point. To achieve a normalized NCC concentration, participants must have demonstrated 2 consecutive measures within the normal range (0.8 to 2.3 μmol/L). Analyses includes all data up to the last assessment in the extension period for participants who reached the event of normalization of NCC corrected concentrations. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. Change from Baseline in the UWDRS I for consciousness is presented. UWDRS I: range 0 to 3, maximum score of 3 UWDRS I was assessed by a Neurologist Change from Baseline was calculated as: Week 24 score - Baseline score. A decrease in score from Baseline is indicative of both an improvement in condition and a better outcome.
Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. UWDRS comprises 3 parts: UWDRS I (consciousness), UWDRS II (disability), and UWDRS III (neurological status). Change from Baseline in the UWDRS II, III, and total score are presented. UWDRS I: range 0 to 3, maximum score of 3 UWDRS II: range 0 to 40, maximum score of 40 UWDRS III: range 0 to 175, maximum score of 175 UWDRS total score: sum of the UWDRS I, II, and III: range 0 to 218, maximum score of 218 UWDRS I and III were assessed by a neurologist, while UWDRS II was reported by the participant or caregiver. Change from Baseline was calculated as: Week 24 score - Baseline score. Least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. A decrease in score from Baseline is indicative of an improvement in condition and a better outcome.
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
The M.I.N.I. is a short structured diagnostic interview for the Diagnostic and Statistical Manual of Mental Disorders IV and the 10th revision of the International Statistical Classification of Diseases and Related Health Problems. It was used to "track" the severity of symptoms by using a combination of questions in 16 Psychiatric Status dimensions that are summarized using a single standardized score for each dimension, ranging from 0 (interpreted as "did not occur at all") to 4 (interpreted as "occurred extremely often"). The standardized score is an average of these responses. Change from Baseline = Week 24 standardized score - Baseline standardized score. Least square means and 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. Decrease from Baseline (a lower score) is indicative of a decrease in symptoms and a better outcome.
Clinical Global Impression-Improvement Scale (CGI-I) At Week 24
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated 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. Change from Baseline = Week 24 score - Baseline score. An increase in CGI-I score indicates improvement.
Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) At Week 24
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at 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. Change from Baseline = Week 24 score - Baseline score. Decrease in CGI-S score and increase indicates improvement.
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The European Quality Of Life 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) At Week 24
The EQ-5D VAS records the participant's self-rated health as indicated on a scale from 0 to 100 with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine, with higher scores for a higher quality of life. Change from Baseline = Week 24 score - Baseline score. An increase in score indicates improvement. The least-square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The EQ-5D Descriptive System UK Health Index Scores At Week 24
The EQ-5D-5L Descriptive System provides a simple descriptive profile and a single index value for health status (United Kingdom [UK] Health Index Score). The EQ-5D-5L consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can have 1 of 5 responses that represent 5 levels of severity (no problems, slight problems, moderate problems, severe problems, extreme problems). The participant was asked to indicate his/her health state for each of the 5 dimensions. The 5-item index score was transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from Baseline = Week 24 index score - Baseline index score. An increase in score indicates improvement. The least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
QoL/PRO Assessed By The 8-Item Medication Adherence Scale (MMAS-8) At Week 24
The MMAS-8 is a scale used to evaluate adherence to medication. The MMAS-8 consists of 8 questions with a sum score ranging between 0 and 8 points, with 8 being the maximum adherence to medication. Mean adherence to medication is presented.
QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
The TSQM-9 was used to assess the overall level of satisfaction or dissatisfaction with medication participants were taking. This composite scale is comprised of 2 items on the TSQM-9 survey: How satisfied are you that good things about this medication outweigh the bad things? Taking all things into account, how satisfied or dissatisfied are you with this medication? The TSQM-9 domain scores (effectiveness score, convenience score, global satisfaction score) range from 0 to 100 with higher scores representing greater satisfaction for the domain.
Change From Baseline In Hepatic Laboratory Measure Alanine Aminotransferase (ALT) At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 ALT level - Baseline ALT level.
Change From Baseline In Hepatic Laboratory Measure Aspartate Aminotransferase (AST) At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 AST level - Baseline AST level.
Change From Baseline In Hepatic Laboratory Measure International Normalized Ratio (INR) At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 INR - Baseline INR.
Change From Baseline In Hepatic Laboratory Measure Bilirubin At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 bilirubin level - Baseline bilirubin level.
Change From Baseline In Exchangeable Cu At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 Exchangeable Cu level - Baseline Exchangeable Cu level.
Change From Baseline In Speciation Profiling (Mo, Cu, And Protein Complex Profiling Using Size Exclusion Chromatography) At Week 24
Due to low chromatographic resolution of data, quantitative analysis for speciation profiling, as had been planned in the protocol, was not feasible.
Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24
Assessed by laboratory measurements. Change from Baseline = Week 24 (24-hour) urinary Mo or Cu level - Baseline 24-hour urinary Mo or Cu level.
Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
PK: Maximum Concentration (Cmax) Of Plasma Total Mo
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
Extension Period: Percentage Of Participants With Normalized Concentrations Of NCC
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8-2.3 μM) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of Cu bound to Cp from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Extension Period: Change From Baseline In NCC Levels Adjusted For Mo Plasma Concentration
The change from Baseline in NCC adjusted for Mo plasma concentration over 176 weeks were analyzed. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period, up to Week 176. Change from Baseline = (Last assessment [up to Week 176] NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.

Full Information

First Posted
October 20, 2014
Last Updated
September 28, 2021
Sponsor
Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT02273596
Brief Title
Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients
Official Title
A Phase 2, Multi-centre, Open-label, Study to Evaluate the Efficacy and Safety of WTX101 Administered for 24 Weeks in Newly Diagnosed Wilson Disease Patients Aged 18 and Older With an Extension Phase of 36 Months
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
November 24, 2014 (Actual)
Primary Completion Date
October 27, 2016 (Actual)
Study Completion Date
November 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of the study was to evaluate the efficacy of ALXN1840 (formerly WTX101) for 24 weeks on non-ceruloplasmin-bound copper (NCC) concentrations adjusted for molybdenum plasma concentration in participants newly diagnosed with Wilson Disease (WD) who were aged 18 and older and who had NCC concentrations within or above the reference range at the time of enrollment in the study. The study consisted of a 24-week Treatment Period, followed by a planned 36-month Extension Period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wilson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ALXN1840
Arm Type
Experimental
Arm Description
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligram (mg) per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks. Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range. ALXN1840 could have been received for up to 36 months in the Extension Period.
Intervention Type
Drug
Intervention Name(s)
ALXN1840
Other Intervention Name(s)
WTX101
Intervention Description
Individualized oral doses of ALXN1840.
Primary Outcome Measure Information:
Title
Percentage Of Participants With Normalized Concentrations Of NCC
Description
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole [μmol]l/liter [L]]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24
Description
The change from Baseline in NCC adjusted for Mo plasma concentration over 24 weeks were analyzed and descriptive statistics are reported. Change from Baseline = (Week 24 NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% confidence intervals (CIs) were calculated using a restricted maximum likelihood (REML)-based mixed model for repeated measures (MMRM) with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Time Frame
Baseline, Week 24
Title
Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC
Description
For time to normalization of NCC adjusted for Mo plasma concentration, a Kaplan-Meier approach was used where participants not normalized were censored at the latest observed time point. To achieve a normalized NCC concentration, participants must have demonstrated 2 consecutive measures within the normal range (0.8 to 2.3 μmol/L). Analyses includes all data up to the last assessment in the extension period for participants who reached the event of normalization of NCC corrected concentrations. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Time Frame
Up to last assessment (up to Week 176)
Title
Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24
Description
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. Change from Baseline in the UWDRS I for consciousness is presented. UWDRS I: range 0 to 3, maximum score of 3 UWDRS I was assessed by a Neurologist Change from Baseline was calculated as: Week 24 score - Baseline score. A decrease in score from Baseline is indicative of both an improvement in condition and a better outcome.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
Description
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. UWDRS comprises 3 parts: UWDRS I (consciousness), UWDRS II (disability), and UWDRS III (neurological status). Change from Baseline in the UWDRS II, III, and total score are presented. UWDRS I: range 0 to 3, maximum score of 3 UWDRS II: range 0 to 40, maximum score of 40 UWDRS III: range 0 to 175, maximum score of 175 UWDRS total score: sum of the UWDRS I, II, and III: range 0 to 218, maximum score of 218 UWDRS I and III were assessed by a neurologist, while UWDRS II was reported by the participant or caregiver. Change from Baseline was calculated as: Week 24 score - Baseline score. Least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. A decrease in score from Baseline is indicative of an improvement in condition and a better outcome.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Description
The M.I.N.I. is a short structured diagnostic interview for the Diagnostic and Statistical Manual of Mental Disorders IV and the 10th revision of the International Statistical Classification of Diseases and Related Health Problems. It was used to "track" the severity of symptoms by using a combination of questions in 16 Psychiatric Status dimensions that are summarized using a single standardized score for each dimension, ranging from 0 (interpreted as "did not occur at all") to 4 (interpreted as "occurred extremely often"). The standardized score is an average of these responses. Change from Baseline = Week 24 standardized score - Baseline standardized score. Least square means and 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. Decrease from Baseline (a lower score) is indicative of a decrease in symptoms and a better outcome.
Time Frame
Baseline, Week 24
Title
Clinical Global Impression-Improvement Scale (CGI-I) At Week 24
Description
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated 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. Change from Baseline = Week 24 score - Baseline score. An increase in CGI-I score indicates improvement.
Time Frame
Week 24
Title
Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) At Week 24
Description
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at 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. Change from Baseline = Week 24 score - Baseline score. Decrease in CGI-S score and increase indicates improvement.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The European Quality Of Life 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) At Week 24
Description
The EQ-5D VAS records the participant's self-rated health as indicated on a scale from 0 to 100 with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine, with higher scores for a higher quality of life. Change from Baseline = Week 24 score - Baseline score. An increase in score indicates improvement. The least-square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The EQ-5D Descriptive System UK Health Index Scores At Week 24
Description
The EQ-5D-5L Descriptive System provides a simple descriptive profile and a single index value for health status (United Kingdom [UK] Health Index Score). The EQ-5D-5L consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can have 1 of 5 responses that represent 5 levels of severity (no problems, slight problems, moderate problems, severe problems, extreme problems). The participant was asked to indicate his/her health state for each of the 5 dimensions. The 5-item index score was transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from Baseline = Week 24 index score - Baseline index score. An increase in score indicates improvement. The least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Time Frame
Baseline, Week 24
Title
QoL/PRO Assessed By The 8-Item Medication Adherence Scale (MMAS-8) At Week 24
Description
The MMAS-8 is a scale used to evaluate adherence to medication. The MMAS-8 consists of 8 questions with a sum score ranging between 0 and 8 points, with 8 being the maximum adherence to medication. Mean adherence to medication is presented.
Time Frame
Week 24
Title
QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
Description
The TSQM-9 was used to assess the overall level of satisfaction or dissatisfaction with medication participants were taking. This composite scale is comprised of 2 items on the TSQM-9 survey: How satisfied are you that good things about this medication outweigh the bad things? Taking all things into account, how satisfied or dissatisfied are you with this medication? The TSQM-9 domain scores (effectiveness score, convenience score, global satisfaction score) range from 0 to 100 with higher scores representing greater satisfaction for the domain.
Time Frame
Week 24
Title
Change From Baseline In Hepatic Laboratory Measure Alanine Aminotransferase (ALT) At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 ALT level - Baseline ALT level.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Hepatic Laboratory Measure Aspartate Aminotransferase (AST) At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 AST level - Baseline AST level.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Hepatic Laboratory Measure International Normalized Ratio (INR) At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 INR - Baseline INR.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Hepatic Laboratory Measure Bilirubin At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 bilirubin level - Baseline bilirubin level.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Exchangeable Cu At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 Exchangeable Cu level - Baseline Exchangeable Cu level.
Time Frame
Baseline, Week 24
Title
Change From Baseline In Speciation Profiling (Mo, Cu, And Protein Complex Profiling Using Size Exclusion Chromatography) At Week 24
Description
Due to low chromatographic resolution of data, quantitative analysis for speciation profiling, as had been planned in the protocol, was not feasible.
Time Frame
Baseline, Week 24
Title
Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24
Description
Assessed by laboratory measurements. Change from Baseline = Week 24 (24-hour) urinary Mo or Cu level - Baseline 24-hour urinary Mo or Cu level.
Time Frame
Baseline, Week 24
Title
Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
Description
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
Time Frame
0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24
Title
PK: Maximum Concentration (Cmax) Of Plasma Total Mo
Description
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
Time Frame
0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24
Title
Extension Period: Percentage Of Participants With Normalized Concentrations Of NCC
Description
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8-2.3 μM) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of Cu bound to Cp from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Time Frame
Up to last assessment (up to Week 176)
Title
Extension Period: Change From Baseline In NCC Levels Adjusted For Mo Plasma Concentration
Description
The change from Baseline in NCC adjusted for Mo plasma concentration over 176 weeks were analyzed. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period, up to Week 176. Change from Baseline = (Last assessment [up to Week 176] NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Time Frame
Baseline, last assessment (up to Week 176)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator. Newly established diagnosis of WD by Leipzig-Score ≥ 4 documented by testing as outlined in 2012 European Association for the Study of the Liver Wilson Disease Clinical Practice Guidelines. NCC levels within or above the normal reference range (0.8 to 2.3 micromole). Willing to undergo 48 hour washout from current WD treatment Exclusion Criteria: Treatment for greater than 24 months for WD with chelation therapy (for example, penicillamine, trientine hydrochloride) or zinc therapy. Decompensated hepatic cirrhosis. Model for End-Stage Liver Disease score > 11. Modified Nazer score > 6. Gastrointestinal bleed within past 6 months. Alanine aminotransferase > 5 x upper limit of normal. Marked neurological disease requiring either nasogastric feeding or intensive in-patient medical care. Severe anemia with a hemoglobin < 9 grams/deciliter.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugene Swenson, MD, PhD
Organizational Affiliation
Alexion
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Clinical Trial Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Clinical Trial Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Clinical Trial Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Clinical Trial Site
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Clinical Trial Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Clinical Trial Site
City
Warsaw
ZIP/Postal Code
02-957
Country
Poland
Facility Name
Clinical Trial Site
City
Guildford
State/Province
Surrey
ZIP/Postal Code
GU27XX
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28988934
Citation
Weiss KH, Askari FK, Czlonkowska A, Ferenci P, Bronstein JM, Bega D, Ala A, Nicholl D, Flint S, Olsson L, Plitz T, Bjartmar C, Schilsky ML. Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):869-876. doi: 10.1016/S2468-1253(17)30293-5. Epub 2017 Oct 5.
Results Reference
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Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients

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