Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
Condition: Wilson Disease
MeSH terms: Hepatolenticular Degeneration
Intervention: ALXN1840; SoC Therapy
Intervention description: ALXN1840 administered orally in 15 mg tablets; Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.
Intervention MeSH terms: Tetrathiomolybdate; Choline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking description: This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
Enrollment: 214.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Wilson Disease; ALXN1840; Copper

Summary:

      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.
    

Eligibility criteria:

        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