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

Wilson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04573309
• Other study ID #: ALXN1840-WD-204
• Secondary ID: 2020-001104-41
• Status: Completed
• Phase: Phase 2
• Start date: September 7, 2020
• Est. completion date: September 1, 2022

Study information

• Verified date: October 2023
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 1, 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Wilson Disease

Intervention

Drug:
• ALXN1840
Administered orally as tablets.

Locations

Country	Name	City	State
New Zealand	Clinical Study Site	Grafton	Auckland
United Kingdom	Clinical Study Site	London
United States	Clinical Study Site	Lincoln	Nebraska
United States	Clinical Study Site	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum		Day 1 up to Day 39
Secondary	Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum		Day 39