Wilson Disease MedDRA version: 20.0 Level: LLT Classification code 10047988 Term: Wilson's disease System Organ Class: 100000004850
Conditions
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participants must be aged 3 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Decompensated hepatic cirrhosis. 2. MELD score > 13 (ages 12 to 13 (ages 3 to 7. 4. Clinically significant gastrointestinal (GI) bleed within past 3 months 5. Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) for participants treated for > 28 days with WD therapy (Cohort 1). 6. ALT > 5 × ULN for treatment naïve participants or participants who have been treated for = 28 days (Cohort 2) 7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care. 8. Hemoglobin less than lower limit of the reference range for age and sex. 9. History of seizure activity within 6 months prior to informed consent/assent. Prior/Concomitant Therapy 10. Previous use of ALXN1840 or ammonium tetrathiomolybdate; concomitant use of penicillamine, trientine, or zinc (for participants randomized to ALXN1840). Prior/Concurrent Clinical Study Experience 11. The use of an investigational drug within 30 days before initiation of the first dose of study intervention. Diagnostic assessments 12. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5 [CKD 5]) or estimated glomerular filtration rate 14 units for males or > 7 units for females per week. One unit is equivalent to 14 g of alcohol: a half pint (approx. 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. 19. Abuse of illicit or prescribed drugs. 20. In the opinion of the Investigator, the participant and/or their parent/proxy is likely to be non-compliant or uncooperative during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ALXN1840 administered for 48 weeks, compared to SoC, on copper control in participants with WD aged 3 to < 18 years of age at the time of enrollment;Secondary Objective: - Evaluate the safety and tolerability of ALXN1840 administered for up to 48 weeks. - Evaluate PD and biomarkers of ALXN1840 vs SoC administered for 48 weeks. - Evaluate the effects of ALXN1840 and SoC on the NCC responder rate. - Evaluate the effects of ALXN1840 and SoC on participant reported disability status. - Evaluate the effects of ALXN1840 and SoC on rater-blinded neurological status. - Evaluate PK of ALXN1840 administered for 48 weeks. - Evaluate the effects of ALXN1840 and SoC on global clinical symptoms as assessed by the Investigator. - Evaluate the effects of ALXN1840 and SoC on hepatic status.;Primary end point(s): Percentage change from baseline (Day 1) to 48 weeks in NCC in plasma. For ALXN1840-treated participants, the NCC in plasma will be corrected for the amount of copper bound to the ALXN1840 TPC (NCCcorrected);Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of adverse AEs/SAEs, AESIs, tolerability, clinical laboratory test data (including liver function tests), neurological and physical examination findings, 12-lead ECG data, and vital signs. • AUEC for NCC • AUEC for plasma total copper • Biomarkers: observed, absolute and percentage changes of ceruloplasmin-bound copper and ceruloplasmin • NCC responder rate • Change from baseline to Week 48 in the UWDRS Part II total score • Change from baseline in UWDRS Part III total score or individual items/subscales, as appropriate • PK: Cmax, tmax, AUCtau and t1/2 on Day 1, Day 43 (Week 6), and Day 337 (Week 48) for plasma total molybdenum and plasma ultrafiltrate molybdenum concentrations, accumulation ratio of Day 43 to Day 1 and Day 337 to Day 1 based on Cmax and AUCtau • Derived population PK parameters such as apparent total body clearance (CL/F) and apparent volume of distribution (Vd/F) • CGI-I • Change from Baseline to Week 48 in CGI-S • Change from Baseline to Week 48 in MELD score (ages 12 years and older) or PELD score (ages 3 to < 12 years) • Change from Baseline to Week 48 in Modified Nazer score;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Countries
Australia, Austria, Canada, Czechia, Denmark, France, Germany, Hungary, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Serbia, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactAnna Anguera
Alexion Pharma Spain S.L.
Outcome results
None listed