Study of ALXN1840 Versus Standard of Care in Pediatric Pa... | NCT05047523

NCT05047523

ID	Type	Description	Link
2021-001015-82	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ALXN1840	Experimental	ALXN1840 will be administered at one of two starting doses, with incremental dose increases permitted.	Drug: ALXN1840
Standard of Care	Active Comparator	Participants will receive their current therapy or initiate Standard of Care therapy.	Drug: Standard of Care

Name	Type	Description	Arm Group Labels	Other Names
ALXN1840	Drug	Administered as an oral tablet.	ALXN1840	Formerly WTX101

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Eugene S. Swenson, MD, PhD	Alexion Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Parkville		VIC 3052	Australia
Research Site

References Module

Label	URL
Related Info	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 8, 2022	Jun 20, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

FG00015 subjects
FG00116 subjects
FG0024 subjects
FG0035 subjects
FG0040 subjects
FG0050 subjects

Full Analysis Set (FAS) included all participants who received at least 1 dose of ALXN1840 or SoC treatment.

Arm/Group Information

ID	Title	Description
BG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in PEP.
BG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in PEP.
BG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in PEP.
BG003	Cohort 2: SoC Therapy	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received SoC therapy according to the local package label for up to 48 weeks in PEP.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Children (2-11 years)	BG0006 BG0016 BG0023 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0005 BG0014 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

FAS included all participants who received at least 1 dose of ALXN1840 or SoC treatment. Due to the early termination of the study, data for this Outcome Measure were not collected for any of the cohorts.

Posted

Baseline, Week 48

ID	Title	Description
OG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.
OG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG003	Cohort 2: SoC Therapy	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received SoC therapy according to the local package label for up to 48 weeks in the PEP.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

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.

Safety analysis set included all participants who received at least 1 dose of ALXN1840 or SoC treatment.

Posted

Count of Participants

Participants

Baseline up to Week 48

ID	Title	Description
OG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.

Secondary

Area Under the Effect Versus Time Curve (AUEC) for Plasma Total Copper and Direct NCC

Pharmacodynamic (PD) analysis set included all participants who had sufficient plasma samples to enable the calculation of pharmacokinetic (PK) parameters and provide PK/PD profiles. Here, 'Overall number of participants analyzed' = participants evaluable for this Outcome Measure. No participants were evaluable for this Outcome Measure for Cohort 2: ALXN1840.

Posted

Mean

Standard Deviation

nanograms (ng)*hours (hr)/milliliter(mL)

Week 48

ID	Title	Description
OG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.
OG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.

Secondary

Maximum Observed Concentration (Cmax) of ALXN1840 for Plasma Total Molybdenum and Plasma Ultrafiltrate Molybdenum Concentrations

PK analysis set included all participants who had sufficient plasma samples to enable the calculation of PK parameters and provide PK/PD profiles. Here, 'Overall number of participants analyzed' = participants evaluable for this Outcome Measure. No participants were evaluable for this Outcome Measure for Cohort 2: ALXN1840.

Posted

Mean

Standard Deviation

ng/mL

Week 48

ID	Title	Description
OG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.
OG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.

Secondary

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

Posted

Mean

Standard Deviation

ng*hr/mL

Week 48

ID	Title	Description
OG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.
OG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.
OG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: ALXN1840	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.	15	0	15	13	15
EG001	Cohort 1: SoC Therapy	Participants in Cohort 1 (who received SoC therapy, that is, chelation therapy with penicillamine or trientine, zinc therapy, or a combination of both chelation and zinc therapy for >28 days) continued to receive SoC therapy according to the local package label for up to 48 weeks in the PEP.	16	2	16	12	16
EG002	Cohort 2: ALXN1840	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received titrated doses of ALXN1840 orally for up to 48 weeks in the PEP.	4	0	4	2	4
EG003	Cohort 2: SoC Therapy	Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received SoC therapy according to the local package label for up to 48 weeks in the PEP.	5	0	5	4	5
EG004	ALXN1840/ALXN1840	Participants who were randomized to the ALXN1840 group during the PEP and who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 24 additional weeks.	12	0	12	6	12
EG005	SoC Therapy/ALXN1840	Participants who were randomized to the SoC group during the PEP and who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 24 additional weeks.	12	0	12	8	12

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Duodenal perforation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG0030 events0 affected5 at risk EG0040 events0 affected12 at risk EG0050 events0 affected12 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0011 events1 affected16 at risk EG0021 events1 affected4 at risk EG0030 events0 affected5 at risk EG0040 events0 affected12 at risk EG0050 events0 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 events3 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0021 events1 affected4 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0021 events1 affected4 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected16 at risk EG0020 events0 affected4 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected16 at risk EG0020 events0 affected4 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0011 events1 affected16 at risk EG0023 events1 affected4 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0006 events6 affected15 at risk EG0014 events4 affected16 at risk EG0020 events0 affected4 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected15 at risk EG0011 events1 affected16 at risk EG0022 events1 affected4 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 events1 affected15 at risk EG0013 events3 affected16 at risk EG0020 events0 affected4 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0014 events3 affected16 at risk EG0020 events0 affected4 at risk EG003
Viral infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected16 at risk EG0020 events0 affected4 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0007 events6 affected15 at risk EG0010 events0 affected16 at risk EG0022 events1 affected4 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected16 at risk EG0022 events1 affected4 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Blood triglycerides increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Electrocardiogram abnormal	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected16 at risk EG0021 events1 affected4 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected16 at risk EG0021 events1 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected16 at risk EG0020 events0 affected4 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected15 at risk EG0011 events1 affected16 at risk EG0021 events1 affected4 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0012 events2 affected16 at risk EG0020 events0 affected4 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected15 at risk EG0012 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected16 at risk EG0020 events0 affected4 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected16 at risk EG0020 events0 affected4 at risk EG003

Due to early termination of the study, data for the efficacy endpoints were not collected.

Certain Agreements

First MCP Posted Date

ID	Term
D006527	Hepatolenticular Degeneration

Ancestor Terms

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D009069	Movement Disorders
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008661	Metabolism, Inborn Errors
D008664	Metal Metabolism, Inborn Errors
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D059039	Standard of Care