Clinical trial NCT04573309: Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840
Official title: A Phase 2, Open-label Study to Assess Copper and Molybdenum Balance in Participants With Wilson Disease Treated With ALXN1840
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wilson Disease
Keywords: Copper Balance
Molybdenum Balance
Wilson Disease
ALXN1840
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Daily Copper Balance: Day 1 Through Day 8
timeFrame: Accumulation: Day 1 through Day 8 (ALXN1840 15 mg)
measure: Mean Daily Copper Balance: Day 31 Through Day 35
timeFrame: Accumulation: Day 31 through Day 35 (ALXN1840 30 mg)
measure: Mean Daily Copper Balance: Day 25 Through Day 28
timeFrame: Accumulation: Day 25 through Day 28 (ALXN1840 15 mg)
measure: Mean Daily Copper Balance: Day 36 Through Day 39
timeFrame: Accumulation: Day 36 through Day 39 (ALXN1840 30 mg)
Secondary outcomes:
measure: Change From Baseline In Mean Daily Copper Balance
timeFrame: 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)
measure: Copper Quantified In Food, Drink, Feces, And Urine, Including Plasma Total And Labile Bound Copper (LBC)
timeFrame: 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
measure: Molybdenum Specified In ALXN1840 Doses Given And Quantified In Food, Drink, Feces, And Urine, Including Plasma At Steady State
timeFrame: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
measure: Change From Baseline In Total Molybdenum Excretion In Urine And Feces
timeFrame: 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)
measure: Mean Daily Molybdenum Balance At ALXN1840 Steady State
timeFrame: Steady state: Day 25 through Day 28 (ALXN1840 15 mg) and Day 36 through Day 39 (ALXN1840 30 mg)
measure: Accumulation Of Molybdenum As Determined By Molybdenum Balance
timeFrame: Accumulation: Day 1 through Day 8 (ALXN1840 15 mg) and Day 31 through Day 35 ((ALXN1840 30 mg)
measure: Maximum Observed Plasma Concentration (Cmax) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum
timeFrame: Day 1 up to Day 39
measure: Area Under The Concentration Time Curve (AUC0-inf) of Total Molybdenum and Plasma Ultrafiltrate (PUF) Molybdenum
timeFrame: Day 39
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Grafton
country: New Zealand
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Eugene S. Swenson, MD, PhD
role: STUDY_DIRECTOR
affiliation: Alexion Pharmaceuticals, Inc.
name: Peter Ksenuk, MD
role: STUDY_DIRECTOR
References: