Phase 3, open-label study of ALXN1840 versus standard of care in pediatric participants with Wilson disease

JRCT ID: jRCT2011210038

Registered date:05/10/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Wilson disease
• Date of first enrollment: 27/10/2021
• Target sample size: 48
• Countries of recruitment: Australia,Japan,South Korea,Japan,UK,Japan,US,Japan,Spain,Japan,France,Japan,Germany,Japan,Poland,Japan
• Study type: Interventional

Intervention(s)

- Participants aged 12 to < 18 years: starting dose of 15 mg/day, if necessary, reduce the dose according to the dose reduction instructions in the study protocol.
- Participants aged 3 to < 12 years: starting dose of 2.5 mg/day, with increase in increments of 2.5 mg up to 14 mg/day

Outcome(s)

• Primary Outcome: Percentage change from baseline (Day 1) to 48 weeks in NCC in plasma. For ALXN1840-treated participants, the NCC in plasma will be corrected for the amount of copper bound to the ALXN1840 TPC (NCCcorrected)

Secondary Outcome

- Incidence of AEs/SAEs, AESIs, tolerability, clinical laboratory test data (including liver function tests), neurological and physical examination findings, 12-lead ECG data, and vital signs.
- AUEC for NCC
- AUEC for plasma total copper
- Biomarkers: observed, absolute and percentage changes of ceruloplasmin-bound copper and ceruloplasmin
- Change from baseline to Week 48 in the UWDRS Part II total score
- Change from baseline in UWDRS Part III total score or individual items/subscales, as appropriate
- Change from Baseline to Week 48 in MELD score (ages 12 years and older) or PELD score (ages 3 to < 12 years)
- Change from Baseline to Week 48 in Modified Nazer score

Key inclusion & exclusion criteria

• Age minimum: >= 3age old
• Age maximum: < 18age old
• Gender: Both

Include criteria

- Established diagnosis of WD by Leipzig-Score over 4 documented by testing as outlined in the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines (Ferenci 2003. EASL 2012). Note: Historical test results for WD, including some or all of the following: presence of KF rings, neurologic symptoms, serum ceruloplasmin below the reference range, Coombs-negative hemolytic anemia, elevated liver or urinary copper, presence of mutations in the ATP7B gene, or other, as considered appropriate, may be used instead to confirm the diagnosis of Wilson disease.
- Participant's parent or proxy must be willing and able to give written informed consent and the participant must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board (IRB) or Institutional (or Independent) Ethics Committee (IEC)). If allowable per local regulations, a participant's Legally Acceptable Representative (LAR) may provide informed consent if a participant is unable to do so.
- Adequate venous access to allow collection of required blood samples.
- Able to swallow intact ALXN1840 tablets or mini-tablets. Participants who require gastrostomy devices for feeding or medications may be enrolled upon agreement by the Medical Monitor.
- Willing to avoid intake of foods and drinks with high contents of copper throughout the study duration

Exclude criteria

- Decompensated hepatic cirrhosis.
- MELD score more than 13 (ages 12 to less than 18) or PELD score more than 13 (ages 3 to less than 12).
- Modified Nazer score more than 7 (Dhawan, 2005).
- Clinically significant gastrointestinal (GI) bleed within past 3 months
- Alanine aminotransferase (ALT) more than 2 times upper limit of normal (ULN) for participants treated for more than 28 days with WD therapy (Cohort 1).
- ALT more than 5 times ULN for treatment naive participants or participants who have been treated for under 28 days (Cohort 2)

Related Information

• Primary Sponsor: Kobayashi Hiroshi
• Secondary ID(s): NCT05047523