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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 August 2023
• Main ID: NCT03403205
• Date of registration: 19/12/2017
• Prospective Registration: Yes
• Primary sponsor: Alexion
• Public title: Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
• Scientific title: 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
• Date of first enrolment: February 15, 2018
• Target sample size: 214
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03403205
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Russian Federation, Serbia, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Eugene S. Swenson, M.D., Ph.D.
• Affiliation: Alexion

Key inclusion & exclusion 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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Wilson Disease

Intervention(s)

Drug: ALXN1840

Drug: SoC Therapy

Primary Outcome(s)

Daily Mean Area Under The Effect-time Curve (AUEC) Of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) [Time Frame: Baseline to 48 weeks]

Secondary Outcome(s)

Change From Baseline In The Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Clinical Global Impression-Improvement Scale (CGI-I) [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Change From Baseline In Model For End-Stage Liver Disease (MELD) Score [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Effects of ALXN1840 on NCC responder rate [Time Frame: Baseline (Day 1) to 48 weeks]

Effects of ALXN1840 on neurological status, as assessed by UWDRS Part III individual items/subscales (arising from a chair, gait, handwriting, and speech) [Time Frame: Baseline (Day 1) to 48 weeks]

Global effects of ALXN1840 on clinical symptoms as assessed by the Investigator on the Clinical Global Impression-Improvement Scale (CGI-I) and the Clinical Global Impression-Severity Scale (CGI-S) [Time Frame: Baseline (Day 1) to 48 weeks]

Number Of Participants With Treatment-emergent Adverse Events [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Effects of ALXN1840 on hepatic status [Time Frame: Baseline (Day 1) to 48 weeks]

Change From Baseline In Calculated NCC (cNCC) In Plasma [Time Frame: Baseline (Day 1), 48 weeks]

Change From Baseline In UWDRS Part III Total Score And Individual Items/Subscales (Arising From A Chair, Gait, Handwriting, And Speech) [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

cNCC Responder Rate [Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Change From Baseline In cNCC In Plasma. [Time Frame: Baseline, 48 weeks]

Effects of ALXN1840 on disability status [Time Frame: Baseline (Day 1) to 48 weeks]

Secondary ID(s)

2017-004135-36

WTX101-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors