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

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04573309
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 20.7
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Wilson Disease	Drug: ALXN1840	Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study to Assess Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840
• Actual Study Start Date: Sep 7, 2020
• Anticipated Primary Completion Date: May 31, 2022
• Anticipated Study Completion Date: May 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Daily Copper Balance [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 will be calculated as the average daily copper balance over the collection period.

2. Mean Daily Copper Balance [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 will be calculated as the average daily copper balance over the collection period.

3. Mean Daily Copper Balance [Steady state: 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 will be calculated as the average daily copper balance over the collection period.

4. Mean Daily Copper Balance [Steady state: 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 will be calculated as the average daily copper balance over the collection period.

Secondary Outcome Measures

1. 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 31 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 will be calculated as the average daily copper balance over the collection period.

2. 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 will be 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.

3. 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)]

   Molybdenum balance is defined as the difference between the measured molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine), and will be calculated as the average daily molybdenum balance over the collection period.

4. 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)]

5. Mean Daily Molybdenum Balance At 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 will be 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).

6. Accumulation Of Molybdenum As Determined By Molybdenum Balance [Accumulation: Day 1 through Day 8 for 15 mg and Day 31 through Day 35 for 30 mg]

   Molybdenum balance will be assessed through measurement of molybdenum intake (in food, drink, and ALXN1840), and molybdenum output (in feces and urine).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Study Site	New Haven	Connecticut	United States	06520
2	Clinical Study Site	Lincoln	Nebraska	United States	68502
3	Clinical Study Site	Grafton	Auckland	New Zealand	1010
4	Clinical Study Site	London		United Kingdom	London SE1 1YR

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

• Study Director: Eugene S. Swenson, MD, PhD, Alexion Pharmaceuticals
• Study Director: Peter Ksenuk, MD, Alexion Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04573309
• Other Study ID Numbers: ALXN1840-WD-204; 2020-001104-41
• First Posted: Oct 5, 2020
• Last Update Posted: May 18, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion Pharmaceuticals: Copper Balance; Molybdenum Balance; Wilson Disease; ALXN1840
• Additional relevant MeSH terms: Hepatolenticular Degeneration

Study Results

No Results Posted as of May 18, 2022