Study of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease

Phase 3

Terminated

• Conditions: Wilson Disease
• Interventions: Drug: Standard of Care; Drug: ALXN1840

• Registration Number: NCT05047523
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

This study is being conducted to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics of ALXN1840 versus standard of care in pediatric participants with Wilson disease (WD).

Detailed Description

Participants who complete the 48 weeks of treatment in Period 1 will have the option to receive ALXN1840 for 24 weeks in Period 2 (open-label extension).

Safety will be monitored throughout the study.

Study Timeline

• Study First Submitted: 2021-09-09
• Study First Submitted QC: 2021-09-09
• Study Start: 2021-09-13
• Study First Posted: 2021-09-17
• Primary Completion: 2023-06-26
• Study Completion: 2023-06-26
• Results First Submitted: 2024-06-20
• Results First Submitted QC: 2024-09-16
• Status Verified: 2024-10
• Results First Posted: 2024-10-15
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Diagnosis of Wilson Disease by Leipzig Score ≥ 4.
2. Adequate venous access to allow collection of required blood samples.
3. Able to swallow intact ALXN1840 tablets or mini-tablets.
4. Willing to avoid intake of foods and drinks with high contents of copper.
5. Willing and able to follow protocol-specified contraception requirements.

Key

Exclusion Criteria

1. Decompensated hepatic cirrhosis or MELD score > 13 (ages 12 to <18) or PELD score > 13 (ages 3 to < 12).
2. Modified Nazer score > 7.
3. Clinically significant gastrointestinal bleed within past 3 months.
4. Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) for participants treated for > 28 days with WD therapy or ALT > 5 × ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days.
5. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
6. Hemoglobin less than lower limit of the reference range for age and sex.
7. History of seizure activity within 6 months prior to informed consent/assent.
8. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5) or estimated glomerular filtration rate < 30 milliliters/minute/1.73 meter squared.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Participants will receive their current therapy or initiate Standard of Care therapy.
ALXN1840	ALXN1840	ALXN1840 will be administered at one of two starting doses, with incremental dose increases permitted.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 48 in Non-ceruloplasmin-bound Copper in Plasma	Baseline, Week 48	Plasma samples were planned to be collected to measure ceruloplasmin-bound copper. Due to the early termination of the study, data for this Outcome Measure were not collected for any of the cohorts.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Primary Evaluation Period	Baseline up to Week 48	An adverse event (AE) was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs with onset after the first dose of study intervention or existing events that worsened in severity after the first dose of study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Area Under the Effect Versus Time Curve (AUEC) for Plasma Total Copper and Direct NCC	Week 48
Maximum Observed Concentration (Cmax) of ALXN1840 for Plasma Total Molybdenum and Plasma Ultrafiltrate Molybdenum Concentrations	Week 48
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) of ALXN1840 for Plasma Total Molybdenum and Plasma Ultrafiltrate Molybdenum	Week 48

Trial Locations

Locations (1)

Research Site; 🇪🇸 Pamplona, Spain