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

A Multicenter, Randomized, Controlled, Open-label, Rater-blinded Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN1840 Versus Standard of Care in Pediatric Participants With Wilson Disease

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).

Study Overview

• Status: Terminated
• Conditions: Wilson Disease
• Intervention / Treatment: Drug: ALXN1840; Drug: Standard of Care

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, VIC 3052
    • Research Site
  • South Brisbane, Australia, 4101
    • Research Site
• France
  • Lille, France, 59037
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Germany
  • Hannover, Germany, 30625
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
• Japan
  • Kumamoto-shi, Japan, 860-8556
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Meguro-ku, Japan, 153-8515
    • Research Site
  • Sapporo-shi, Japan, 063-0005
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
• Poland
  • Warsaw, Poland, 04-730
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Esplugues de Llobregat, Spain, 8950
    • Research Site
  • Las Palmas de Gran Canaria, Spain, 35016
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Málaga, Spain, 29011
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1840; ALXN1840 will be administered at one of two starting doses, with incremental dose increases permitted.	Drug: ALXN1840; Administered as an oral tablet.; Other Names: Formerly WTX101
Active Comparator: Standard of Care; Participants will receive their current therapy or initiate Standard of Care therapy.	Drug: Standard of Care; Depending on the site/region, participants randomized to receive Standard of Care treatment will receive trientine, penicillamine, zinc, or a combination of these medicines, administered according to standard regimens.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Week 48 in Non-ceruloplasmin-bound Copper in Plasma	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.	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Primary Evaluation Period	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.	Baseline up to Week 48
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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Investigators: Study Director: Eugene S. Swenson, MD, PhD, Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): June 26, 2023
• Study Completion (Actual): June 26, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; Wilson Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metal Metabolism, Inborn Errors; Hepatolenticular Degeneration
• Other Study ID Numbers: ALXN1840-WD-302; 2021-001015-82 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No