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

• Register: EUCTR
• Last refreshed on: 1 February 2022
• Main ID: EUCTR2019-003711-60-DK
• Date of registration: 19/06/2020
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc
• Public title: A Phase 2 clinical study to assess copper levels and liver changes in patients with Wilson disease who are treated with ALXN1840
• Scientific title: A Phase 2, single-arm, pathologist-blinded study using liver biopsy specimens to assess copper concentration and histopathologic changes in patients with Wilson disease who are treated with ALXN1840 for 48 weeks followed by an extension treatment period with ALXN1840 for up to an additional 48 weeks
• Date of first enrolment: 27/08/2020
• Target sample size: 28
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003711-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Pathologist Blinded; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, France, Germany, Korea, Republic of, New Zealand, Poland, Russian Federation, Serbia, Singapore, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Martine Zimmerman
• Affiliation: Alexion Europe SAS

• Name: Martine Zimmerman
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Wilson's Disease
MedDRA version: 20.0 Level: LLT Classification code 10047988 Term: Wilson's disease System Organ Class: 100000004850

Intervention(s)

Product Name: ALXN1840
Product Code: ALXN1840
Pharmaceutical Form: Tablet
INN or Proposed INN: Not applied
CAS Number: 649749-10-0
Current Sponsor code: ALXN1840
Other descriptive name: BIS-CHOLINE TETRATHIOMOLYBDATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 48

Primary end point(s): Change from baseline to Week 48 in liver Cu concentration

Secondary Objective: The secondary objectives are to:
- To assess change in liver histopathology following treatment with ALXN1840
- To evaluate the safety of ALXN1840 in patients with WD
- To evaluate pharmacokinetics (PK) of ALXN1840
- To evaluate the effects of ALXN1840 on clinical symptoms
please see study protocol for more details.

Main Objective: To evaluate change in liver copper (Cu) concentration following treatment with ALXN1840 at Week 48 in patients with Wilson disease (WD)

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints include the following:
- Change from baseline to Week 48 in steatosis, inflammation, and fibrosis
- Adverse events (AEs), vital signs, ECGs, clinical laboratory data, and physical examination data
- ALXN1840 PK profiles in plasma at Week 6 (Day 43) and Week 36 (Day 253), of which ALXN1840 PK are measured as total molybdenum (Mo) and plasma ultrafiltrate (PUF) Mo
- Pre-dose trough ALXN1840 concentrations in plasma at each study site visit
- ALXN1840 concentrations in the liver biopsy specimen.
- Change from baseline in Clinical Global Impression-Improvement (CGI-I) Scale and the Clinical Global Impression-Severity (CGI-S) Scale

Timepoint(s) of evaluation of this end point: Week 48

Secondary ID(s)

2019-003711-60-DE

ALXN1840-WD-205

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc

Ethics review

Status: Approved
Approval date: 27/08/2020
Contact: