Phase 2
N=31
Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
Wilson Disease
Bottom Line
View on ClinicalTrials.gov: NCT04422431 ↗Enrolled (actual)
31
Serious AEs
8.9%
Results posted
Jul 2023
Primary outcome: Primary: Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) — 92.8 μg/g — p=0.1002
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bis-Choline Tetrathiomolybdate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) |
92.8 | 0.1002 |
| SECONDARY Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) |
7; 1; 0; 7; 3; 8 | — |
| SECONDARY Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) |
8; 7; 4; 7; 2; 1 | — |
| SECONDARY Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) |
8; 6; 2; 9; 1; 1 | — |
| SECONDARY Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period) |
8.5445 | — |
| SECONDARY Change From Baseline in a-SMA Content at Week 48 (Treatment Period) |
1.6002 | — |
| SECONDARY Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) |
19; 6; 3; 1; 15; 6 | — |
| SECONDARY Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period) |
-0.2504 | — |
| SECONDARY Change From Baseline in NAS Total Score at Week 48 (Treatment Period) |
0.1 | — |
| SECONDARY Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
30 | — |
| SECONDARY Extension Period: Number of Participants With TEAEs |
24 | — |
| SECONDARY Treatment Period: Predose Trough Plasma Total Mo Concentration |
174.39; 131.19 | — |
| SECONDARY Treatment Period: Predose Trough Plasma Total PUF Mo Concentration |
5.888; 7.843 | — |
| SECONDARY Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period) |
69.6976 | — |
| SECONDARY Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period) |
3.1 | — |
| SECONDARY Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period) |
-0.4 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.
- Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
- Body mass index 13.
- Modified Nazer score > 7.
- Clinically significant gastrointestinal bleed within past 3 months.
- Alanine aminotransferase > 2 × upper limit of normal.
- History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time ≥ 1.5.
- Participant unwilling to accept blood products, if required.
- Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
- Hemoglobin less than lower limit of the reference range for age and sex.
- Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute.
- Lymphoma, leukemia, or any malignancy within the past 5 years.
- Current or chronic history of liver disease not associated with WD.
Data sourced from ClinicalTrials.gov (NCT04422431). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.