Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840

Study Overview
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Brief Summary
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This exploratory study will investigate the effects of ALXN1840 on copper balance in participants with Wilson disease (WD).

Detailed Description
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Participants who are treatment experienced (which includes standard-of-care therapies or ALXN1840) and treatment naïve are eligible for this study.

Official Title
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A Phase 2, Open-label Study to Assess Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840

Conditions
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Wilson Disease

Intervention / Treatment
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* Drug: ALXN1840


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of WD by Leipzig Criteria ≥ 4. Able to reside in the clinical research unit for intensive metabolic monitoring of copper and molybdenum. Participants willing to adhere to copper/molybdenum-controlled diet during the study. Willing and able to follow protocol-specified contraception requirements. Capable of giving signed informed consent. Exclusion Criteria: Decompensated cirrhosis or model for end stage liver disease score > 13. Modified Nazer score > 7. Clinically significant gastrointestinal bleed within past 3 months. Alanine aminotransferase > 2 × upper limit of normal. Hemoglobin less than lower limit of the reference range for age and sex. Significant medical history (current or past). Previous treatment with zinc within 30 days prior to the Screening Visit. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance < 30 milliliters/minute.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1840<br>Participants will be administered ALXN1840 at a dose of 15 milligrams (mg)/day on Day 1 through Day 28 and then increased to 30 mg/day on Day 29 through Day 39 | Drug: ALXN1840<br>* Administered orally as tablets.<br>* Other names: formerly WTX101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Copper Balance: Day 1 Through Day 8 | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. | Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) | 
| Mean Daily Copper Balance: Day 31 Through Day 35 | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. | Accumulation: Day 31 through Day 35 (ALXN1840 30 mg) | 
| Mean Daily Copper Balance: Day 25 Through Day 28 | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. | Accumulation: Day 25 through Day 28 (ALXN1840 15 mg) | 
| Mean Daily Copper Balance: Day 36 Through Day 39 | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. | Accumulation: Day 36 through Day 39 (ALXN1840 30 mg) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline In Mean Daily Copper Balance | Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period. | Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | 
| Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC) | Copper was assessed through measurement of copper intake (in food and drink), and copper output (in feces and urine) as well as plasma total and labile bound copper. | Accumulation: Day 1 through Day 8 for 15 mg and Day 31 through Day 35 for 30 mg; Steady state: Day 25 through Day 28 for ALXN1840 15 mg and Day 36 through Day 39 for ALXN1840 30 mg | 
| Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State | The amount of molybdenum in food, drink, feces and urine is reported in this outcome measure. | Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | 
| Change From Baseline In Total Molybdenum Excretion In Urine And Feces |  | Accumulation: Baseline, Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 (ALXN1840 30 mg); Steady State: Baseline, Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | 
| Mean Daily Molybdenum Balance At ALXN1840 Steady State | Molybdenum balance at steady state was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine). Steady state is defined as molybdenum (out) equal to molybdenum (in). | Steady state: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg) | 
| Accumulation Of Molybdenum As Determined By Molybdenum Balance | Molybdenum balance was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine). | Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 ((ALXN1840 30 mg) | 
| Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum |  | Day 1 up to Day 39 | 
| Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum |  | Day 39 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Copper Balance, Molybdenum Balance, Wilson Disease, ALXN1840