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 Contact: Name: Alexion Pharmaceuticals, Inc.; Phone Number: +1 855-752-2356; Email: clinicaltrials@alexion.com

Study Locations

• Australia
  • Parkville, Australia, VIC 3052
    • Clinical Trial Site
  • South Brisbane, Australia, 4101
    • Clinical Trial Site
• France
  • Bron, France, 69667
    • Clinical Trial Site
  • Lille, France, 59037
    • Clinical Trial Site
  • Paris, France, 7515
    • Clinical Trial Site
  • Paris, France, 94270
    • Clinical Trial Site
  • Toulouse, France, 31059
    • Clinical Trial Site
• Germany
  • Hamburg, Germany, 20246
    • Clinical Trial Site
  • Hanover, Germany, 30625
    • Clinical Trial Site
  • Tuebingen, Germany, 72076
    • Clinical Trial Site
• Japan
  • Chiba, Japan, 266-0007
    • Clinical Trial Site
  • Kumamoto, Japan, 860-8556
    • Clinical Trial Site
  • Kurume, Japan, 830-0011
    • Clinical Trial Site
  • Meguro-Ku, Japan, 153-8515
    • Clinical Trial Site
  • Sapporo, Japan, 063-0005
    • Clinical Trial Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Clinical Trial Site
  • Seoul, Korea, Republic of, 03080
    • Clinical Trial Site3
  • Seoul, Korea, Republic of, 06351
    • Clinical Trial Site 2
• Poland
  • Warsaw, Poland, 04-730
    • Clinical Trial Site
• Spain
  • Barcelona, Spain, 08035
    • Clinical Trial Site
  • Barcelona, Spain, 08950
    • Clinical Trial Site
  • Las Palmas de Gran Canaria, Spain, 35016
    • Clinical Trial Site
  • Madrid, Spain, 28041
    • Clinical Trial Site
  • Malaga, Spain, 29010
    • Clinical Trial Site
  • Pamplona, Spain, 31008
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom, SE59RS
    • Clinical Trial 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	Time Frame
Percentage Change From Baseline To Week 48 In Non-ceruloplasmin-bound Copper (NCC) In Plasma	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under The Effect Versus Time Curve (AUEC) For NCC And Plasma Total Copper	Week 48
Observed Change From Baseline To Week 48 Of Ceruloplasmin-bound Copper And Ceruloplasmin	Baseline, Week 48
NCC Responder Rate	Week 48
Change From Baseline To Week 48 In The UWDRS Part II Total Score	Baseline, Week 48
Change From Baseline To Week 48 In The UWDRS Part III Total Score	Baseline, Week 48
PK: Maximum Observed Concentration (Cmax) Of ALXN1840 For Plasma Total Molybdenum And Plasma Ultrafiltrate Molybdenum Concentrations	Up to Week 48
PK: Time To Maximum Concentration (Tmax) Of ALXN1840 For Plasma Total Molybdenum And Plasma Ultrafiltrate Molybdenum Concentrations	Up to Week 48
PK: 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 Concentrations	Up to Week 48
Clinical Global Impression-improvement (CGI-I), As Assessed By The Investigator	Week 48
Change From Baseline To Week 48 In Clinical Global Impression-severity (CGI-S), As Assessed By The Investigator	Baseline, Week 48
Change From Baseline To Week 48 In Model For End-stage Liver Disease (MELD) Score (Ages 12 Years And Older) Or Pediatric End-stage Liver Disease (PELD) Score (Ages 3 To < 12 Years)	Baseline, Week 48
Change From Baseline To Week 48 In Modified Nazer Score	Baseline, Week 48

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 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 (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Wilson Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; 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