Wilson Disease (WD) MedDRA version: 20.0 Level: LLT Classification code 10047988 Term: Wilson's disease System Organ Class: 100000004850
Conditions
Interventions
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
Concen
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants aged =18 at the time of signing the ICF. 2. Diagnosis of WD by Leipzig Criteria > 4 documented by testing as outlined in the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines 3. Participants who in the opinion of the referring Investigator may benefit from decoppering therapy. 4. Participants must be able to comply with all study-related procedures. 5. Participants must be able to reside in the CRU for intensive metabolic monitoring of Cu and Mo. 6. Participants willing to discontinue chelator therapy for approximately 4 days prior to initiation of ALXN1840 to allow a baseline assessment of Cu balance. 7. Participants with adequate venous access to allow collection of required blood samples. 8. Participants must be able to swallow intact ALXN1840 tablets. 9. Participants willing to avoid use of minerals containing Cu, Zn, or Mo throughout the study duration. 10. Participants willing to adhere to Cu/Mo-controlled diet during inpatient periods and willing to comply with a low Cu dietary requirement during the Outpatient Period. 11. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 12. Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Decompensated cirrhosis or model for end-stage liver disease (MELD) score > 13. 2. Modified Nazer score > 7. 3. Clinically significant gastrointestinal bleed within past 3 months. 4. Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN). 5. Marked neurological disease requiring assistance with self-care or activities of daily life. 6. Hemoglobin less than lower limit of the reference range for age and sex. 7. Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus (participants with positive hepatitis C antibody result would require confirmation of active disease with a positive hepatitis C polymerase chain reaction test), or seropositivity for human immunodeficiency virus (HIV). 8. History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders, or psychiatric disorder that in the opinion of the Investigator may constitute a risk when taking the study intervention; or may interfere with the interpretation of data. 9. Previous treatment with ALXN1840 or other form of tetrathiomolybdate within 1 year prior to dosing. 10. Previous treatment with zinc within 30 days prior to the Screening Visit. 11. Participation in a clinical study of an experimental or unapproved/unlicensed therapy at the same time or within 90 days or 5 half-lives, whichever is longer, prior to the Screening Visit. 12. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease [CKD] stage 5) or creatinine clearance < 30 mL/min. 13. Pregnant (or females who are planning to become pregnant) or breastfeeding females (women of childbearing potential must have a negative serum pregnancy test result at screening). 14. Known sensitivity to ALXN1840, ALXN1840 excipients (anhydrous dicalcium phosphate, anhydrous sodium carbonate), or any of the ingredients contained in ALXN1840 or related compounds. 15. In the opinion of the Investigator, the participant and/or their legal guardian is likely to be non-compliant or uncooperative during the study. 16. History of illicit drug abuse, history of significant alcohol abuse within 1 year prior to the Screening Visit, or clinical evidence of substance and/or alcohol abuse within the 2 years before screening. Alcohol abuse is defined as regular weekly intake of more than 14 units (for both males and females), using the following National Health Service (NHS) alcohol tracker http://www.nhs.uk/Tools/Pages/drinks-tracker.aspx. 17. Positive urine drug toxicology screen at Screening or on Day -8. 18. Alcohol consumption within 48 hours prior to study intervention administration or positive alcohol breath test at screening or on Day -8. 19. Participants unwilling to consistently complete every meal and tolerate a controlled, limited menu for the duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess net copper (Cu) balance with daily repeat-dose ALXN1840 treatment (15 mg and 30 mg) in participants with Wilson disease (WD);Secondary Objective: • Assess change in Cu balance in response to ALXN1840 15 mg/day and 30 mg/day during ALXN1840 accumulation and at steady state periods versus the pretreatment baseline in participants with WD • Investigate the effect of ALXN1840 (15 mg/day and 30 mg/day) on the disposition of Cu in participants with WD • Investigate the effect of ALXN1840 on the disposition of molybdenum (Mo) at steady state at 15 mg/day and 30 mg/day in participants with WD • Assess steady-state total Mo balance as a measure of ALXN1840 15 mg/day and 30 mg/day in participants with WD • Assess accumulation of Mo with ALXN1840 treatment at 15 mg/day and 30 mg/day in participants with WD • Determine the steady-state plasma pharmacokinetic (PK) of total Mo and plasma ultrafiltrate (PUF) Mo (as surrogate measures of ALXN1840, 15 mg and 30 mg) in participants with WD.;Primary end point(s): Mean daily Cu balance where Cu balance is measured by the calculated difference between Cu intake (in food and drink) and Cu output (in feces and urine) during ALXN1840 accumulation and steady-state periods for each dose.;Timepoint(s) of evaluation of this end point: Day 1-8, Day 25-28, Day 31-35 and Day 36-39 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in mean daily Cu balance as measured by the calculated difference between Cu intake (in food and drink) and Cu output (in feces and urine) from pretreatment baseline (Days -4 through -1) and ALXN1840 accumulation and steady-state periods for each dose • Copper quantified in food, drink, feces, and urine, including plasma total and labile bound Cu (LBC) during ALXN1840 accumulation and steady-state periods for each dose • Molybdenum quantified in food, drink, feces, and urine, plasma total Mo at ALXN1840 steady state • Mean daily Mo balance as demonstrated through measurement of Mo intake (in food, drink, and ALXN1840), and Mo output (feces and urine) representing ALXN1840 steady state • Accumulation of Mo as determined by Mo balance • PK parameters for plasma total and PUF-Mo;Timepoint(s) of evaluation of this end point: Day 1, Day 4-7, Day 14, Day 25-40 | — |
Countries
United Kingdom
Contacts
Public ContactNathalie Boeglin
Alexion Europe S.A.S.
Outcome results
None listed