Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Wilson Disease

Treatments: Drug: Bis-Choline Tetrathiomolybdate

Study type: Interventional

Funder types: Industry

Identifiers

NCT04422431

2019-003711-60 (EudraCT Number)

ALXN1840-WD-205

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

31 participants in 1 patient group

ALXN1840

Experimental group

Description:

Participants will receive ALXN1840.

Treatment:

Drug: Bis-Choline Tetrathiomolybdate