Clinical trial NCT04422431: Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
Official title: A Phase 2, Single-arm Pathologist-blinded 48-week Study Using Liver Biopsy Specimens to Assess Copper Concentration and Histopathologic Changes in ALXN1840-treated Patients With Wilson Disease Followed by an up to 48-weeks Extension Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wilson Disease
Keywords: Copper
ALXN1840
Histology
Liver Biopsy
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 31
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: The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). In the Treatment Period, efficacy and safety of ALXN1840 will be assessed at Week 48.

Detailed description: Participants who complete the 48-week Treatment Period will be offered the opportunity to continue their treatment in a 48-week Extension Period that will offer additional time for evaluation of long-term efficacy and safety of ALXN1840. There will be no liver biopsies during the Extension Period.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.
2. Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
3. Body mass index \< 30 kilograms/meter squared.
4. Able to cooperate with a percutaneous liver biopsy.
5. Willing and able to follow protocol-specified contraception requirements.
6. 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. History of bleeding abnormality or known coagulopathy, including platelet count \< 100,000, and international normalized ratio for prothrombin time ≥ 1.5.
6. Participant unwilling to accept blood products, if required.
7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
8. Hemoglobin less than lower limit of the reference range for age and sex.
9. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance \< 30 milliliters/minute.
10. Lymphoma, leukemia, or any malignancy within the past 5 years.
11. Current or chronic history of liver disease not associated with WD.

Primary outcomes:
measure: Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
Secondary outcomes:
measure: Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Change From Baseline in a-SMA Content at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Change From Baseline in NAS Total Score at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (Treatment Period) up to Week 48 (Treatment Period)
measure: Extension Period: Number of Participants With TEAEs
timeFrame: Day 1 (Extension Period) up Week 52 (Extension Period)
measure: Treatment Period: Predose Trough Plasma Total Mo Concentration
timeFrame: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
measure: Treatment Period: Predose Trough Plasma Total PUF Mo Concentration
timeFrame: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
measure: Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
measure: Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)
timeFrame: Week 48 (Treatment Period)
measure: Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)
timeFrame: Baseline, Week 48 (Treatment Period)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Research Site
state: California
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Århus N
country: Denmark
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Valencia
country: Spain
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
References: