Clinical trial NCT02273596: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wilson Disease
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-24
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage Of Participants With Normalized Concentrations Of NCC
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24
timeFrame: Baseline, Week 24
measure: Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC
timeFrame: Up to last assessment (up to Week 176)
measure: Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
timeFrame: Baseline, Week 24
measure: Clinical Global Impression-Improvement Scale (CGI-I) At Week 24
timeFrame: Week 24
measure: Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) At Week 24
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: QoL/PRO Assessed By The 8-Item Medication Adherence Scale (MMAS-8) At Week 24
timeFrame: Week 24
measure: QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
timeFrame: Week 24
measure: Change From Baseline In Hepatic Laboratory Measure Alanine Aminotransferase (ALT) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Hepatic Laboratory Measure Aspartate Aminotransferase (AST) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Hepatic Laboratory Measure International Normalized Ratio (INR) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Hepatic Laboratory Measure Bilirubin At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Exchangeable Cu At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Speciation Profiling (Mo, Cu, And Protein Complex Profiling Using Size Exclusion Chromatography) At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24
timeFrame: Baseline, Week 24
measure: Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24
measure: PK: Maximum Concentration (Cmax) Of Plasma Total Mo
timeFrame: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24
measure: Extension Period: Percentage Of Participants With Normalized Concentrations Of NCC
timeFrame: Up to last assessment (up to Week 176)
measure: Extension Period: Change From Baseline In NCC Levels Adjusted For Mo Plasma Concentration
timeFrame: Baseline, last assessment (up to Week 176)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: New Haven
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: Vienna
country: Austria
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Warsaw
country: Poland
facility: Clinical Trial Site
city: Guildford
country: United Kingdom
facility: Clinical Trial Site
state: Surrey
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Eugene Swenson, MD, PhD
role: STUDY_DIRECTOR
References:
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.