Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease

A Phase 3, Randomized, Rater-Blinded, Multi-Center Study to Evaluate the Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Patients With Wilson Disease Aged 12 Years and Older, With an Extension Period of up to 60 Months

The study will evaluate the efficacy and safety of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson Disease (WD) participants aged 12 and older in the Primary Evaluation Period. In addition, efficacy and safety will be evaluated during an optional 60-month Extension Period.

The study consists of 2 cohorts. Cohort 1: Participants who have received SoC therapy for > 28 days and Cohort 2: Participants who are treatment-naïve or who have received SoC therapy for ≤ 28 days.

All enrolled participants were randomized by cohort in a 2:1 ratio to treatment with ALXN1840 or SoC (either as continued therapy in Cohort 1 or as continued or initial therapy in Cohort 2).

Key Inclusion Criteria:

• Established diagnosis of WD by Leipzig-Score ≥ 4
• Female participants of childbearing potential, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception starting at least 6 weeks before the Day 1 visit and continuing through 28 days after the last dose of either ALXN1840 or SoC
• Male participants, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception beginning at Day 1 visit and continuing through 90 days after last dose of either ALXN1840 or SoC

Key Exclusion Criteria:

• Decompensated hepatic cirrhosis
• MELD score > 13
• Modified Nazer score > 7
• Clinically significant gastrointestinal bleed within past 3 months
• Alanine aminotransferase > 2 X upper limit of normal (ULN) for participants treated for > 28 days with WD therapy (Cohort 1)
• Alanine aminotransferase > 5 X ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days (Cohort 2)
• Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care
• Hemoglobin < 9 grams/deciliter
• History of seizure activity within 6 months prior to informed consent
• Pregnant (or women who are planning to become pregnant) or breastfeeding women
• Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus or seropositivity for human immunodeficiency virus (HIV)
• Previous treatment with tetrathiomolybdate
• Participants with end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance < 30 milliliter/minute