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

Phase 2

Completed

Conditions: Wilson Disease

Interventions: Drug: ALXN1840

Registration Number: NCT04573309

Lead Sponsor: Alexion Pharmaceuticals, Inc.

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

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALXN1840	ALXN1840	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

Primary Outcome Measures

Name	Time	Method
Mean Daily Copper Balance: Day 36 Through Day 39	Accumulation: Day 36 through Day 39 (ALXN1840 30 mg)	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.
Mean Daily Copper Balance: Day 1 Through Day 8	Accumulation: Day 1 through Day 8 (ALXN1840 15 mg)	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.
Mean Daily Copper Balance: Day 31 Through Day 35	Accumulation: Day 31 through Day 35 (ALXN1840 30 mg)	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.
Mean Daily Copper Balance: Day 25 Through Day 28	Accumulation: Day 25 through Day 28 (ALXN1840 15 mg)	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline In Mean Daily Copper Balance	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 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.
Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC)	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	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.
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	Steady state: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)	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).
Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State	Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)	The amount of molybdenum in food, drink, feces and urine is reported in this outcome measure.
Accumulation Of Molybdenum As Determined By Molybdenum Balance	Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 ((ALXN1840 30 mg)	Molybdenum balance was assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine).
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