Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease

Study Overview
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Brief Summary
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This study is being conducted to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics of ALXN1840 versus standard of care in pediatric participants with Wilson disease (WD).

Detailed Description
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Participants who complete the 48 weeks of treatment in Period 1 will have the option to receive ALXN1840 for 24 weeks in Period 2 (open-label extension). Safety will be monitored throughout the study.

Official Title
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A Multicenter, Randomized, Controlled, Open-label, Rater-blinded Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease

Conditions
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Wilson Disease

Intervention / Treatment
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* Drug: ALXN1840
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of Wilson Disease by Leipzig Score ≥ 4. Adequate venous access to allow collection of required blood samples. Able to swallow intact ALXN1840 tablets or mini-tablets. Willing to avoid intake of foods and drinks with high contents of copper. Willing and able to follow protocol-specified contraception requirements. Key Exclusion Criteria: Decompensated hepatic cirrhosis or MELD score > 13 (ages 12 to <18) or PELD score > 13 (ages 3 to < 12). Modified Nazer score > 7. Clinically significant gastrointestinal bleed within past 3 months. Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) for participants treated for > 28 days with WD therapy or ALT > 5 × ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care. Hemoglobin less than lower limit of the reference range for age and sex. History of seizure activity within 6 months prior to informed consent/assent. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5) or estimated glomerular filtration rate < 30 milliliters/minute/1.73 meter squared.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1840<br>ALXN1840 will be administered at one of two starting doses, with incremental dose increases permitted. | Drug: ALXN1840<br>* Administered as an oral tablet.<br>* Other names: Formerly WTX101;|
| Active Comparator: Standard of Care<br>Participants will receive their current therapy or initiate Standard of Care therapy. | Drug: Standard of Care<br>* Depending on the site/region, participants randomized to receive Standard of Care treatment will receive trientine, penicillamine, zinc, or a combination of these medicines, administered according to standard regimens.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline To Week 48 In Non-ceruloplasmin-bound Copper (NCC) In Plasma |  | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under The Effect Versus Time Curve (AUEC) For NCC And Plasma Total Copper |  | Week 48 | 
| Observed Change From Baseline To Week 48 Of Ceruloplasmin-bound Copper And Ceruloplasmin |  | Baseline, Week 48 | 
| NCC Responder Rate |  | Week 48 | 
| Change From Baseline To Week 48 In The UWDRS Part II Total Score |  | Baseline, Week 48 | 
| Change From Baseline To Week 48 In The UWDRS Part III Total Score |  | Baseline, Week 48 | 
| PK: Maximum Observed Concentration (Cmax) Of ALXN1840 For Plasma Total Molybdenum And Plasma Ultrafiltrate Molybdenum Concentrations |  | Up to Week 48 | 
| PK: Time To Maximum Concentration (Tmax) Of ALXN1840 For Plasma Total Molybdenum And Plasma Ultrafiltrate Molybdenum Concentrations |  | Up to Week 48 | 
| PK: Area Under The Plasma Concentration Versus Time Curve From Time 0 To The End Of The Dosing Interval (AUCtau) Of ALXN1840 For Plasma Total Molybdenum And Plasma Ultrafiltrate Molybdenum Concentrations |  | Up to Week 48 | 
| Clinical Global Impression-improvement (CGI-I), As Assessed By The Investigator |  | Week 48 | 
| Change From Baseline To Week 48 In Clinical Global Impression-severity (CGI-S), As Assessed By The Investigator |  | Baseline, Week 48 | 
| Change From Baseline To Week 48 In Model For End-stage Liver Disease (MELD) Score (Ages 12 Years And Older) Or Pediatric End-stage Liver Disease (PELD) Score (Ages 3 To < 12 Years) |  | Baseline, Week 48 | 
| Change From Baseline To Week 48 In Modified Nazer Score |  | Baseline, Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wilson Disease, Pediatric