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

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05047523

Collaborator

(none)

Enrollment

Locations

Arms

31.8

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Wilson Disease	Drug: ALXN1840 Drug: Standard of Care	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 6, 2021

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Percentage Change From Baseline To Week 48 In Non-ceruloplasmin-bound Copper (NCC) In Plasma [Baseline, Week 48]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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

Key Exclusion Criteria:

Decompensated hepatic cirrhosis or MELD score > 13 (ages 12 to <18) or PELD score > 13 (ages 3 to < 12).
Modified Nazer score > 7.
Clinically significant gastrointestinal bleed within past 3 months.
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.
Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
Hemoglobin less than lower limit of the reference range for age and sex.
History of seizure activity within 6 months prior to informed consent/assent.
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Clinical Trial Site	Parkville	Australia	VIC 3052
2	Clinical Trial Site	South Brisbane	Australia	4101
3	Clinical Trial Site	Hamburg	Germany	20246
4	Clinical Trial Site	Tuebingen	Germany	72076
5	Clinical Trial Site	Chiba	Japan	266-0007
6	Clinical Trial Site	Kumamoto	Japan	860-8556
7	Clinical Trial Site	Kurume	Japan	830-0011
8	Clinical Trial Site	Meguro-Ku	Japan	153-8515
9	Clinical Trial Site	Sapporo	Japan	063-0005
10	Clinical Trial Site3	Seoul	Korea, Republic of	03080
11	Clinical Trial Site	Seoul	Korea, Republic of	03722
12	Clinical Trial Site 2	Seoul	Korea, Republic of	06351
13	Clinical Trial Site	Warsaw	Poland	04-730
14	Clinical Trial Site	Barcelona	Spain	08035
15	Clinical Trial Site	Barcelona	Spain	08950
16	Clinical Trial Site	Las Palmas de Gran Canaria	Spain	35016
17	Clinical Trial Site	Madrid	Spain	28041
18	Clinical Trial Site	Malaga	Spain	29010
19	Clinical Trial Site	Pamplona	Spain	31008

Sponsors and Collaborators

Alexion Pharmaceuticals

Investigators

Study Director: Eugene S. Swenson, MD, PhD, Alexion Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alexion Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT05047523

Other Study ID Numbers:

ALXN1840-WD-302
2021-001015-82

First Posted:

Sep 17, 2021

Last Update Posted:

Jun 6, 2022

Last Verified:

Jun 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Alexion Pharmaceuticals

Wilson Disease

Pediatric

Additional relevant MeSH terms:

Hepatolenticular Degeneration

Study Results

No Results Posted as of Jun 6, 2022