A Phase 2 clinical study to assess copper levels and liver changes in patients with Wilson disease who are treated with ALXN1840

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 28

Inclusion Criteria

1. Patients must be = 18 years of age at the time of signing the informed consent.
2. Diagnosis of WD by Leipzig Criteria >4 documented by testing as outlined in the 2012 European Association for the Study of Liver (EASL) WD Clinical Practice Guidelines (Ferenci, 2003; EASL, 2012)
3. Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year in duration prior to screening
4. Adequate venous access to allow collection of required blood samples
5. Able to swallow intact ALXN1840 tablets
6. Body mass index < 30 kg/m2
7. Able to cooperate a percutaneous liver biopsy, including having the ability to lie flat and still throughout the procedure, and tolerate mild sedation, if required
8. Adequately visualized landmarks on screening ultrasound without evidence of significant ascites, hemangiomas, or other findings that would put the patient at unnecessarily high risk of complications
9. Male and female patients of reproductive potential must agree to remain abstinent or use an effective method of contraception throughout the duration of the study
10. Capable of giving signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Decompensated cirrhosis or MELD score >13
2. Modified Nazer score > 7 (Dhawan, 2005)
3. Clinically significant gastrointestinal bleed within past 3 months
4. Alanine aminotransferase > 2 × upper limit of normal (ULN)
5. History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time (PT-INR) = 1.5; coagulopathy or bleeding risk due to medication is acceptable if medication can be safety discontinued for biopsy
6. Patient unwilling to accept blood products
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. Systemic disease or other illness, any disability acquired from trauma or another illness, or any deviation in laboratory values that are confirmed on re-examination to be clinically significant by the Investigator
10. Patients in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease [CKD] 5) or creatinine clearance < 30 mL/min
11. Known sensitivity to ALXN1840, ALXN1840 excipients or any of the ingredients contained in ALXN1840
12. History or presence of/significant history of or current cardiovascular, respiratory, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
13. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
14. Current or chronic history of liver disease not associated with WD, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones)
15. Use of nonprescription/ over-the-counter medications, including herbal remedies, nutritional supplements, or mineral supplements containing Cu, zinc, iron or Mo after dosing on Day 1 through the end of the study.
16. In the opinion of the Investigator, the patient and/or their legal guardian is likely to be non-compliant or uncooperative during the study
17. Participation in any other interventional study during the study.
18. Presence of hepatitis B surface antigen or positive hepatitis C antibody or RNA test result at screening or within 3 months prior to first dose of study drug. NOTE: Patients with positive Hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained. NOTE: The RNA test is optional and patients with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
19. Positive human immunodeficiency virus (HIV) antibody test
20. Regular alcohol consumption within 6 months prior to the study defined as > 14 units for males or > 7 units for females per week. One unit is equivalent to 8 g of alcohol: a half pint (approx. 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
21. Abuse of illicit or prescribed drugs
22. Sensitivity to any drug or other allergy that, in the opinion of the Investigator or Alexion Medical Monitor, contraindicates participation in the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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