Efficacy and Safety of ALXN1840 Administered for 48 Weeks... | NCT03403205 | Trialant
NCT03403205
Sponsor
Alexion Pharmaceuticals, Inc.
Status
Terminated
Last Update Posted
Jun 17, 2024Actual
Enrollment
214Actual
Phase
Phase 3
Conditions
Wilson Disease
Interventions
ALXN1840
SoC Therapy
Countries
United States
Australia
Austria
Canada
Czechia
Denmark
France
Germany
Hong Kong
Hungary
Israel
Japan
New Zealand
Poland
Russia
Serbia
Singapore
South Korea
Spain
Taiwan
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03403205
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
WTX101-301
Secondary IDs
ID
Type
Description
Link
2017-004135-36
EudraCT Number
Brief Title
Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
Official Title
A Phase 3, Randomized, Rater-Blinded, Multi-Center Study to Evaluate the Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Patients With Wilson Disease Aged 12 Years and Older, With an Extension Period of up to 60 Months
Acronym
Not provided
Organization
Alexion Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Jun 2024
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Sponsor decision to terminate the program
Expanded Access Info
No
Start Date
Feb 22, 2018Actual
Primary Completion Date
Jun 30, 2023Actual
Completion Date
Jun 30, 2023Actual
First Submitted Date
Dec 19, 2017
First Submission Date that Met QC Criteria
Jan 10, 2018
First Posted Date
Jan 18, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Sep 13, 2023
Results First Submitted that Met QC Criteria
Sep 13, 2023
Results First Posted Date
Oct 10, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 20, 2022
Certification/Extension First Submitted that Passed QC Review
Jan 20, 2022
Certification/Extension First Posted Date
Jan 25, 2022Actual
Last Update Submitted Date
Jun 14, 2024
Last Update Posted Date
Jun 17, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Alexion Pharmaceuticals, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study will evaluate the efficacy and safety of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson Disease (WD) participants aged 12 and older in the Primary Evaluation Period. In addition, efficacy and safety will be evaluated during an optional 60-month Extension Period.
Detailed Description
The study consists of 2 cohorts. Cohort 1: Participants who have received SoC therapy for > 28 days and Cohort 2: Participants who are treatment-naïve or who have received SoC therapy for ≤ 28 days.
All enrolled participants were randomized by cohort in a 2:1 ratio to treatment with ALXN1840 or SoC (either as continued therapy in Cohort 1 or as continued or initial therapy in Cohort 2).
Conditions Module
Conditions
Wilson Disease
Keywords
Wilson Disease
ALXN1840
Copper
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
214Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
ALXN1840
Experimental
ALXN1840 was administered orally for 48 weeks at doses ranging from 15 milligrams (mg) every other day (QOD) up to a titrated dose of 60 mg daily.
Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.
Drug: ALXN1840
Standard of Care (SoC) Medication
Active Comparator
SoC medication was administered for 48 weeks. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.
Drug: SoC Therapy
Interventions
Name
Type
Description
Arm Group Labels
Other Names
ALXN1840
Drug
ALXN1840 administered orally in 15 mg tablets
ALXN1840
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).
Baseline to Week 48
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An 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 those AEs with onset after the first dose of randomized treatment or existing events that worsened in severity after the first dose of randomized treatment. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Established diagnosis of WD by Leipzig-Score ≥ 4
Female participants of childbearing potential, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception starting at least 6 weeks before the Day 1 visit and continuing through 28 days after the last dose of either ALXN1840 or SoC
Male participants, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception beginning at Day 1 visit and continuing through 90 days after last dose of either ALXN1840 or SoC
Key Exclusion Criteria:
Decompensated hepatic cirrhosis
MELD score > 13
Modified Nazer score > 7
Clinically significant gastrointestinal bleed within past 3 months
Alanine aminotransferase > 2 X upper limit of normal (ULN) for participants treated for > 28 days with WD therapy (Cohort 1)
Alanine aminotransferase > 5 X ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days (Cohort 2)
Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care
Hemoglobin < 9 grams/deciliter
History of seizure activity within 6 months prior to informed consent
Pregnant (or women who are planning to become pregnant) or breastfeeding women
Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus or seropositivity for human immunodeficiency virus (HIV)
Previous treatment with tetrathiomolybdate
Participants with end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance < 30 milliliter/minute
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.
All request will be evaluated as per the AZ disclosure commitment:
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Participants were randomized, stratified by cohort, in a 2:1 ratio to treatment with ALXN1840 or continued treatment with Standard of Care (SoC). Two cohorts were defined. Cohort 1: participants previously treated with SoC for >28 days; Cohort 2: participants who were treatment naïve or previously treated with SoC for ≤28 days. Participants who completed participation in Study WTX101-201 (NCT02273596) were offered the opportunity to participate in the Study WTX101-301 OLE Period.
Recruitment Details
The study consisted of 2 periods: Primary Evaluation Period (PEP) and Open-label Extension (OLE) Period. Participants who completed the 48-week PEP were offered the opportunity to continue treatment in an up to 60-month Extension. A total of 214 participants were randomized; 207 participants were treated in the PEP.
Type of Units Analyzed
Not provided
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
Periods
Title
Milestones
Reasons Not Completed
Primary Evaluation Period (48 Weeks)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 27, 2022
Sep 13, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Belgium
Italy
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Single
Masking Description
This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
Who Masked
Outcomes Assessor
Formerly named WTX101
Tiomolibdic acid
Tiomolibdate choline
Bis-choline tetrathiomolybdate
SoC Therapy
Drug
Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.
Standard of Care (SoC) Medication
Baseline up to Week 48
Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items [disability], items 2 to 11 [10 items in total]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 [23 items in total]). The UWDRS Part II total score was calculated as the sum of Question 2 to Question 11 (each question has range 0 [none] to 4 [severe]). The UWDRS Part II total score ranges from 0 (no disability) to 40 (severe disability), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Baseline, Week 48
Change From Baseline in UWDRS Part III Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items [disability], items 2 to 11 [10 items in total]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 [23 items in total]). The UWDRS Part I and III was assessed by a neurologist who was blinded to the treatment randomization. The UWDRS Part III total score was calculated as the sum of Question 12 to Question 34. The UWDRS Part III total score ranges from 0 (normal) to 175 (severe disease), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Baseline, Week 48
Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
UWDRS Part III Functional Subscale consists of speech, handwriting, arising from chair, and gait from UWDRS Part III. The standardized score of the first 3 items ranges from 0 (normal) to 10 (worst), and standardized transformed score of gait ranges from 0 (normal) to 10 (worst). The average of these scores was used to create the Part III Functional Subscale with a range of 0 (normal) - 10 (worst) with higher scores indicating more functional disability.
Baseline, Week 48
Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48
UWDRS Part III individual items speech, handwriting, arising from chair, and gait are reported here. For speech (Question 12), original score ranges from 0 (normal) to 4 (unintelligible). For handwriting (Question 20), original score ranges from 0 (normal) to 4 (cannot hold a pen). For arising from chair (Question 27), original score ranges from 0 (normal) to 4 (unable to arise without help). For gait (Question 29), the original score (range: 0 [normal] to 10 [severe condition]) was calculated by summing subscores (0 [normal] to 4 [severe]) of Part A (Right and Left Leg dystonia), B (Ataxia), and C (Parkinsonism).
Baseline, Week 48
Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Week 48
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at time of rating as: 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Baseline, Week 48
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
The MELD score uses the participant's values for bilirubin, creatinine, and the international normalized ratio (INR). The initial MELD score (MELD[i]) is calculated according to the following formula: MELD(i) = 3.78*ln[serum bilirubin (mg/dL)] + 11.2*ln[INR] + 9.57*ln[serum creatinine (mg/dL)] + 6.43. Creatinine, bilirubin, and INR values less than 1.0 are set to 1.0 and creatinine values greater than 4.0 are set to 4.0 when calculating MELD(i). Additionally, creatinine, bilirubin, and INR are rounded to the 10th decimal place prior to performing the calculation. The initial MELD score is then rounded to the nearest integer. The MELD score ranges from 6 (least sick) - 40 (most sick), with higher values indicating more advanced disease.
Baseline, Week 48
Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48
cNCC = Plasma Total Copper (Cu) [micrograms (µg)/L]-(3.15*ceruloplasmin [milligrams (mg)/L])/63.5 [µg/µmol] For ALXN1840-treated participants, cNCC in plasma corrected for amount of Cu bound to ALXN1840 tripartite complex (TPC) cNCCcorrected = (√cNCC- 0.993)2√Mo, (Mo= molybdenum). In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration <lower limit of quantification (LLOQ), cNCC was considered missing (LLOQ = 20 nanograms [ng]/mL); - Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ = 1 ng/L); - If cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo > √cNCC.
Baseline, Week 48
Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
cNCC [µmol/L] = Plasma Total Cu [µg/L]-(3.15*ceruloplasmin [mg/L])/63.5 [µg/µmol] For ALXN1840-treated participants, cNCC in plasma was corrected for amount of Cu bound to the ALXN1840 TPC using square root-based cNCC correction method: cNCCcorrected = (√cNCC- 0.993)2√Mo, where Mo = molybdenum. In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration values <LLOQ, cNCC was considered missing (LLOQ = 20 ng/mL); - Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ = 1 ng/L); - In cases where cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo > √cNCC.
Baseline, Week 48
cNCC/cNCCcorrected Responder at Week 48
cNCC/cNCCcorrected responder was defined as participants who achieved or maintained normalized cNCC/cNCCcorrected concentration (0.8-2.3 μmol) within (at or before) 48 weeks or reached a reduction of at least 25% in cNCC/cNCCcorrected within 48 weeks. Thus, a participant was considered a cNCC/cNCCcorrected responder if they met at least 1 of the following criteria: - Achieved normalized cNCC/cNCCcorrected concentration for 2 consecutive measurements within 48 weeks, for participants who had elevated cNCC concentrations at baseline; - Maintained normalized cNCC/cNCCcorrected concentration within 48 weeks, for participants who had normal cNCC concentrations at baseline; - Reached a reduction of at least 25% in cNCC/cNCCcorrected for 2 consecutive measurements within 48 weeks.
Week 48
New Haven
Connecticut
06510
United States
Research Site
Chicago
Illinois
60611
United States
Research Site
Ann Arbor
Michigan
48109
United States
Research Site
Houston
Texas
77030
United States
Research Site
Seattle
Washington
98105
United States
Research Site
Adelaide
5000
Australia
Research Site
Concord
2139
Australia
Research Site
Parkville
3050
Australia
Research Site
Parkville
VIC 3052
Australia
Research Site
Graz
8036
Austria
Research Site
Innsbruck
6020
Austria
Research Site
Vienna
1090
Austria
Research Site
Toronto
Ontario
M5G 2C4
Canada
Research Site
Prague
128 08
Czechia
Research Site
Århus N
8200
Denmark
Research Site
Bron
69667
France
Research Site
Paris
75010
France
Research Site
Hamburg
20099
Germany
Research Site
Heidelberg
69120, DE
Germany
Research Site
Leipzig
04103
Germany
Research Site
Hong Kong
852
Hong Kong
Research Site
Budapest
1083
Hungary
Research Site
Jerusalem
9112001
Israel
Research Site
Ramat Gan
5265601
Israel
Research Site
Chiba
266-0007
Japan
Research Site
Kumamoto
860-8556
Japan
Research Site
Kurume-shi
830-0011
Japan
Research Site
Matsuyama
790-0024
Japan
Research Site
Meguro-ku
153-8515
Japan
Research Site
Sapporo
063-0005
Japan
Research Site
Takatsuki-shi
569-8686
Japan
Research Site
Yokohama
230-8765
Japan
Research Site
Grafton
1010
New Zealand
Research Site
Warsaw
02-957
Poland
Research Site
Warsaw
04-730
Poland
Research Site
Moscow
115446
Russia
Research Site
Moscow
117292
Russia
Research Site
Moscow
119021
Russia
Research Site
Nizhny Novgorod
603005
Russia
Research Site
Saint Petersburg
194017
Russia
Research Site
Belgrade
11000
Serbia
Research Site
Singapore
169608
Singapore
Research Site
Daegu
41944
South Korea
Research Site
Barcelona
08036
Spain
Research Site
Málaga
29011
Spain
Research Site
Sabadell
08208
Spain
Research Site
Taipei
10002
Taiwan
Research Site
Taoyuan City
333
Taiwan
Research Site
Ankara
06230
Turkey (Türkiye)
Research Site
Istanbul
34010
Turkey (Türkiye)
Research Site
Istanbul
34093
Turkey (Türkiye)
Research Site
Izmir
35100
Turkey (Türkiye)
Research Site
Edgbaston
B15 2WB
United Kingdom
Research Site
Guildford
GU2 7WG
United Kingdom
Research Site
London
SE5 9RS
United Kingdom
FG001
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
FG002
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
FG003
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
FG004
Cohort 1: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months in the OLE period of this study.
FG005
Cohort 2: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months in the OLE period of this study.
FG000105 subjects
FG00156 subjects
FG00237 subjects
FG00316 subjects
FG0040 subjects
FG0050 subjects
Received at Least 1 Dose of Study Drug
FG000104 subjects
FG00156 subjects
FG00233 subjects
FG00314 subjects
FG0040 subjects
FG0050 subjects
Completed PEP, Enter Extension
FG00089 subjects
FG00149 subjects
FG00228 subjects
FG00312 subjects
FG0040 subjects
FG0050 subjects
Completed PEP, Not Into Extension
FG0004 subjects
FG0013 subjects
FG0021 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG00093 subjects
FG00152 subjects
FG00229 subjects
FG00313 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG00012 subjects
FG0014 subjects
FG0028 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0004 subjects
FG0012 subjects
FG0022 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Adverse Event
FG0004 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Death
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Pregnancy
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Protocol Deviation
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Randomized but not treated
FG0001 subjects
FG0010 subjects
FG0024 subjects
FG0032 subjects
FG004
Extension Period (Up to 60 Months)
Type
Comment
Milestone Data
STARTED
FG00089 subjects
FG00149 subjects
FG00228 subjects
FG00312 subjects
FG0048 subjects
FG00511 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG00089 subjects
FG00149 subjects
FG00228 subjects
FG00312 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0006 subjects
FG0017 subjects
FG0022 subjects
FG003
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized treatment.
The Extension Analysis Set included all participants who entered the Extension Period and received at least 1 dose of ALXN1840 in the Extension Period. This included the participants who rolled over from Study WTX101-201.
Type of Units Analyzed
Not provided
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.
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 for up to 48 weeks according to the local package label.
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.
BG003
Cohort 2: SoC Therapy
Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received/continued to receive SoC therapy for up to 48 weeks according to the local package label.
BG004
Cohort 1: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months.
BG005
Cohort 2: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000104
BG00156
BG00233
BG00314
BG0048
BG00511
BG006226
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
≥12 years - <18 years
BG00010
BG0014
BG0022
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00046
BG00130
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Race
Title
Measurements
Asian
BG00019
BG00113
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0012
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
Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment.
Posted
Least Squares Mean
Standard Error
micromoles (µmol)*hours (hr)/liter (L)
Baseline 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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG000104
OG00156
OG00233
OG003
Title
Denominators
Categories
Title
Measurements
OG0002.50± 0.150(0.150 to )
OG0010.87± 0.204(0.204 to )
OG0024.76± 0.319(0.319 to )
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Analysis was performed using ANCOVA model, which included treatment, cohort, and baseline value. Missing imputation was performed: 1) for intermediate missing, interpolation was used to fill out missing values. 2) For participants who die, baseline dNCC was carried forward from discontinuation to week 48. 3) For others, multiple imputation was used to impute missing dNCC assuming data were missing not at random.
ANCOVA
< 0.0001
Test was performed at a significance level of 0.05.
LS Mean Difference
1.64
Standard Error of the Mean
0.254
2-Sided
95
1.14
2.13
Other
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An 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 those AEs with onset after the first dose of randomized treatment or existing events that worsened in severity after the first dose of randomized treatment. 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 randomized 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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Secondary
Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items [disability], items 2 to 11 [10 items in total]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 [23 items in total]). The UWDRS Part II total score was calculated as the sum of Question 2 to Question 11 (each question has range 0 [none] to 4 [severe]). The UWDRS Part II total score ranges from 0 (no disability) to 40 (severe disability), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
OG001
Secondary
Change From Baseline in UWDRS Part III Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items [disability], items 2 to 11 [10 items in total]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 [23 items in total]). The UWDRS Part I and III was assessed by a neurologist who was blinded to the treatment randomization. The UWDRS Part III total score was calculated as the sum of Question 12 to Question 34. The UWDRS Part III total score ranges from 0 (normal) to 175 (severe disease), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
OG001
Secondary
Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
UWDRS Part III Functional Subscale consists of speech, handwriting, arising from chair, and gait from UWDRS Part III. The standardized score of the first 3 items ranges from 0 (normal) to 10 (worst), and standardized transformed score of gait ranges from 0 (normal) to 10 (worst). The average of these scores was used to create the Part III Functional Subscale with a range of 0 (normal) - 10 (worst) with higher scores indicating more functional disability.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Secondary
Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48
UWDRS Part III individual items speech, handwriting, arising from chair, and gait are reported here. For speech (Question 12), original score ranges from 0 (normal) to 4 (unintelligible). For handwriting (Question 20), original score ranges from 0 (normal) to 4 (cannot hold a pen). For arising from chair (Question 27), original score ranges from 0 (normal) to 4 (unable to arise without help). For gait (Question 29), the original score (range: 0 [normal] to 10 [severe condition]) was calculated by summing subscores (0 [normal] to 4 [severe]) of Part A (Right and Left Leg dystonia), B (Ataxia), and C (Parkinsonism).
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
OG001
Secondary
Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Secondary
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at time of rating as: 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Secondary
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
The MELD score uses the participant's values for bilirubin, creatinine, and the international normalized ratio (INR). The initial MELD score (MELD[i]) is calculated according to the following formula: MELD(i) = 3.78*ln[serum bilirubin (mg/dL)] + 11.2*ln[INR] + 9.57*ln[serum creatinine (mg/dL)] + 6.43. Creatinine, bilirubin, and INR values less than 1.0 are set to 1.0 and creatinine values greater than 4.0 are set to 4.0 when calculating MELD(i). Additionally, creatinine, bilirubin, and INR are rounded to the 10th decimal place prior to performing the calculation. The initial MELD score is then rounded to the nearest integer. The MELD score ranges from 6 (least sick) - 40 (most sick), with higher values indicating more advanced disease.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
units on a scale
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
OG001
Secondary
Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48
cNCC = Plasma Total Copper (Cu) [micrograms (µg)/L]-(3.15*ceruloplasmin [milligrams (mg)/L])/63.5 [µg/µmol] For ALXN1840-treated participants, cNCC in plasma corrected for amount of Cu bound to ALXN1840 tripartite complex (TPC) cNCCcorrected = (√cNCC- 0.993)2√Mo, (Mo= molybdenum). In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration <lower limit of quantification (LLOQ), cNCC was considered missing (LLOQ = 20 nanograms [ng]/mL); - Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ = 1 ng/L); - If cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo > √cNCC.
Full analysis set: all randomized participants who received at least 1 dose of study drug. 'Overall number of participants analyzed'= participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
µmol/L
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
Secondary
Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
cNCC [µmol/L] = Plasma Total Cu [µg/L]-(3.15*ceruloplasmin [mg/L])/63.5 [µg/µmol] For ALXN1840-treated participants, cNCC in plasma was corrected for amount of Cu bound to the ALXN1840 TPC using square root-based cNCC correction method: cNCCcorrected = (√cNCC- 0.993)2√Mo, where Mo = molybdenum. In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration values <LLOQ, cNCC was considered missing (LLOQ = 20 ng/mL); - Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ = 1 ng/L); - In cases where cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo > √cNCC.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Mean
Standard Deviation
percent change
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
Secondary
cNCC/cNCCcorrected Responder at Week 48
cNCC/cNCCcorrected responder was defined as participants who achieved or maintained normalized cNCC/cNCCcorrected concentration (0.8-2.3 μmol) within (at or before) 48 weeks or reached a reduction of at least 25% in cNCC/cNCCcorrected within 48 weeks. Thus, a participant was considered a cNCC/cNCCcorrected responder if they met at least 1 of the following criteria: - Achieved normalized cNCC/cNCCcorrected concentration for 2 consecutive measurements within 48 weeks, for participants who had elevated cNCC concentrations at baseline; - Maintained normalized cNCC/cNCCcorrected concentration within 48 weeks, for participants who had normal cNCC concentrations at baseline; - Reached a reduction of at least 25% in cNCC/cNCCcorrected for 2 consecutive measurements within 48 weeks.
Full analysis set included all randomized participants who received at least 1 dose of randomized treatment.
Posted
Count of Participants
Participants
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
OG001
Cohort 1: SoC Therapy
Time Frame
For PEP participants: From Primary Evaluation Period Baseline up to Primary Evaluation Period Week 48/Early Termination; For OLE and WTX101-201 participants: From Extension Period Week 1 up to Extension Period Week 268/Early Termination
Description
Safety analysis set included all participants who received at least 1 dose of randomized treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
PEP 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.
1
104
14
104
46
104
EG001
PEP 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 for up to 48 weeks according to the local package label.
0
56
6
56
18
56
EG002
PEP 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.
1
33
4
33
16
33
EG003
PEP Cohort 2: SoC Therapy
Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) received SoC therapy for up to 48 weeks according to the local package label.
0
14
0
14
7
14
EG004
OLE 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) who completed the 48-week PEP of study WTX101-301 were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
1
89
20
89
45
89
EG005
OLE 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) who completed the 48-week PEP of study WTX101-301 were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
0
49
10
49
32
49
EG006
OLE Cohort 2: ALXN1840
Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
0
28
6
28
10
28
EG007
OLE Cohort 2: SoC Therapy
Participants in Cohort 2 (who were treatment naïve or who received SoC therapy for ≤28 days) who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
0
12
3
12
4
12
EG008
Cohort 1: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months.
0
8
2
8
6
8
EG009
Cohort 2: WTX101-201- ALXN1840
Participants who received ALXN1840 during Study WTX101-201 (NCT02273596) continued to receive ALXN1840 for up to 60 months.
0
11
3
11
7
11
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Leukopenia
Blood and lymphatic system disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG0030 events0 affected14 at risk
EG0040 events0 affected89 at risk
EG0050 events0 affected49 at risk
EG0060 events0 affected28 at risk
EG0070 events0 affected12 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected11 at risk
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Hepato-lenticular degeneration
Congenital, familial and genetic disorders
MedDRA 26.0
Systematic Assessment
EG0002 events2 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Varices oesophageal
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0003 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Liver disorder
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Epididymitis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Urosepsis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Cystitis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Facial bones fracture
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Gastrostomy tube site complication
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0021 events1 affected33 at risk
EG003
Intentional overdose
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0002 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Rhabdomyolysis
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Hepatocellular carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Lipoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Transitional cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Syncope
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0002 events2 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Dystonia
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0021 events1 affected33 at risk
EG003
Hepatic encephalopathy
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Neurological decompensation
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0022 events1 affected33 at risk
EG003
Epilepsy
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0012 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Device malfunction
Product Issues
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Paranoia
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Persistent depressive disorder
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0021 events1 affected33 at risk
EG003
Aspiration
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0022 events1 affected33 at risk
EG003
Pneumothorax spontaneous
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Venous thrombosis limb
Vascular disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0011 events1 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Coronary artery occlusion
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Supraventricular tachyarrhythmia
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Unevaluable event
General disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Acute hepatic failure
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Hepatic failure
Hepatobiliary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Herpes simplex hepatitis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Retroperitoneal abscess
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Fracture malunion
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Neuropathic arthropathy
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Plasma cell myeloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Transitional cell carcinoma recurrent
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Dyskinesia
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Device dislocation
Product Issues
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Alcoholism
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Depression
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Mental disorder
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Post-traumatic stress disorder
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Ovarian cyst
Reproductive system and breast disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Uterine cyst
Reproductive system and breast disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Microcytic anaemia
Blood and lymphatic system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Acute myocardial infarction
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Umbilical hernia
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Burns second degree
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Sports injury
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected104 at risk
EG0010 events0 affected56 at risk
EG0020 events0 affected33 at risk
EG003
Anal cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008661
Metabolism, Inborn Errors
D008664
Metal Metabolism, Inborn Errors
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C020809
tetrathiomolybdate
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0051 subjects
8 subjects
FG00510 subjects
1 subjects
FG0040 subjects
FG0052 subjects
Adverse Event
FG0006 subjects
FG0013 subjects
FG0021 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Death
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Pregnancy
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Protocol Deviation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Study Terminated by Sponsor
FG00066 subjects
FG00132 subjects
FG00221 subjects
FG00310 subjects
FG0047 subjects
FG0058 subjects
Other than specified
FG0005 subjects
FG0015 subjects
FG0023 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Physician Decision
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
2
BG0040
BG0050
BG00618
≥18 years - <65 years
BG00092
BG00150
BG00231
BG00312
BG0047
BG00511
BG006203
≥65 years
BG0002
BG0012
BG0020
BG0030
BG0041
BG0050
BG0065
9
BG0033
BG0043
BG0057
BG00698
Male
BG00058
BG00126
BG00224
BG00311
BG0045
BG0054
BG006128
5
BG0030
BG0041
BG0051
BG00639
Black or African American
BG0001
BG0012
BG0020
BG0030
BG0040
BG0050
BG0063
White
BG00080
BG00141
BG00227
BG00312
BG0047
BG0059
BG006176
Other
BG0003
BG0010
BG0020
BG0032
BG0040
BG0050
BG0065
Unknown
BG0000
BG0010
BG0021
BG0030
BG0040
BG0050
BG0061
Not Reported
BG0001
BG0010
BG0020
BG0030
BG0040
BG0051
BG0062
0
BG0032
BG0041
BG0050
BG0067
Not Hispanic or Latino
BG000101
BG00154
BG00232
BG00311
BG0047
BG00511
BG006216
Unknown or Not Reported
BG0001
BG0010
BG0021
BG0031
BG0040
BG0050
BG0063
14
OG0030.96± 0.487(0.487 to )
OG002
OG003
Analysis was performed using ANCOVA model, which included treatment, cohort, and baseline value. Missing imputation was performed: 1) for intermediate missing, interpolation was used to fill out missing values. 2) For participants who die, baseline dNCC was carried forward from discontinuation to week 48. 3) For others, multiple imputation was used to impute missing dNCC assuming data were missing not at random.
ANCOVA
< 0.0001
Test was performed at a significance level of 0.05.
LS Mean Difference
3.79
Standard Error of the Mean
0.584
2-Sided
95
2.65
4.94
Other
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG000104
OG00156
OG00233
OG00314
Title
Denominators
Categories
Title
Measurements
OG00089
OG00141
OG00230
OG00312
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00092
OG00150
OG00229
OG00312
Title
Denominators
Categories
Title
Measurements
OG000-0.7± 2.75(2.75 to )
OG0010.0± 2.31(2.31 to )
OG002-0.5± 3.23(3.23 to )
OG003-1.8± 4.63(4.63 to )
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00091
OG00149
OG00228
OG00311
Title
Denominators
Categories
Title
Measurements
OG000-2.24± 7.458(7.458 to )
OG001-1.59± 6.188(6.188 to )
OG002-2.06± 9.843(9.843 to )
OG0031.55± 5.889(5.889 to )
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00091
OG00149
OG00228
OG00311
Title
Denominators
Categories
Title
Measurements
OG000-0.165± 0.7620(0.7620 to )
OG001-0.102± 0.5467(0.5467 to )
OG002-0.090± 0.8464(0.8464 to )
OG0030.227± 0.4214(0.4214 to )
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00091
OG00149
OG00228
OG00311
Title
Denominators
Categories
Speech
ParticipantsOG00091
ParticipantsOG00149
ParticipantsOG00228
ParticipantsOG00311
Title
Measurements
OG000-0.1± 0.50
OG0010.0± 0.35
OG002-0.1± 0.52
OG003
Handwriting
ParticipantsOG00091
ParticipantsOG00148
ParticipantsOG00228
ParticipantsOG00311
Arising from a chair
ParticipantsOG00091
ParticipantsOG00149
ParticipantsOG00228
ParticipantsOG00311
Gait
ParticipantsOG00091
ParticipantsOG00149
ParticipantsOG00228
ParticipantsOG00311
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00092
OG00150
OG00227
OG00312
Title
Denominators
Categories
Title
Measurements
OG0003.4± 0.89(0.89 to )
OG0013.8± 0.80(0.80 to )
OG0023.1± 1.06(1.06 to )
OG0033.2± 1.34(1.34 to )
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00089
OG00147
OG00227
OG00311
Title
Denominators
Categories
Title
Measurements
OG000-0.4± 0.79(0.79 to )
OG001-0.1± 0.73(0.73 to )
OG002-0.6± 1.11(1.11 to )
OG003-0.5± 1.21(1.21 to )
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00086
OG00149
OG00228
OG00311
Title
Denominators
Categories
Title
Measurements
OG000-0.1± 1.85(1.85 to )
OG0010.1± 1.32(1.32 to )
OG002-0.7± 1.61(1.61 to )
OG0030.2± 1.25(1.25 to )
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00063
OG00129
OG00226
OG00310
Title
Denominators
Categories
Title
Measurements
OG000-0.72± 1.107(1.107 to )
OG0010.64± 2.769(2.769 to )
OG002-1.95± 1.536(1.536 to )
OG003-1.51± 2.361(2.361 to )
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
Units
Counts
Participants
OG00060
OG00128
OG00226
OG00310
Title
Denominators
Categories
Title
Measurements
OG000-7.7± 263.20(263.20 to )
OG001104.6± 292.11(292.11 to )
OG002-64.0± 42.88(42.88 to )
OG003-44.3± 68.82(68.82 to )
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. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and continued to receive ALXN1840 for up to 60 months.
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 PEP. Participants who completed the 48-week PEP were offered the opportunity to participate in the OLE Period and received ALXN1840 for up to 60 months.