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

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

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

Study Overview

• Status: Completed
• Conditions: Wilson Disease
• Intervention / Treatment: Drug: ALXN1840

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Grafton, New Zealand, 1010
    • Research Site
• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Research Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of WD by Leipzig Criteria ≥ 4.
2. Able to reside in the clinical research unit for intensive metabolic monitoring of copper and molybdenum.
3. Participants willing to adhere to copper/molybdenum-controlled diet during the study.
4. Willing and able to follow protocol-specified contraception requirements.
5. Capable of giving signed informed consent.

Exclusion Criteria:

1. Decompensated cirrhosis or model for end stage liver disease score > 13.
2. Modified Nazer score > 7.
3. Clinically significant gastrointestinal bleed within past 3 months.
4. Alanine aminotransferase > 2 × upper limit of normal.
5. Hemoglobin less than lower limit of the reference range for age and sex.
6. Significant medical history (current or past).
7. Previous treatment with zinc within 30 days prior to the Screening Visit.
8. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: ALXN1840; Administered orally as tablets.; Other Names: formerly WTX101

What is the study measuring?

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 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)
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)
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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Investigators: Study Director: Eugene S. Swenson, MD, PhD, Alexion Pharmaceuticals, Inc.; Study Director: Peter Ksenuk, MD, Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): June 7, 2022
• Study Completion (Actual): June 7, 2022

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 10, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Copper Balance; Molybdenum Balance; Wilson Disease; ALXN1840
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Metal Metabolism, Inborn Errors; Hepatolenticular Degeneration
• Other Study ID Numbers: ALXN1840-WD-204; 2020-001104-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No