Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03403205
Registration number
NCT03403205
Ethics application status
Date submitted
19/12/2017
Date registered
18/01/2018
Date last updated
10/10/2023
Titles & IDs
Public title
Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
Query!
Scientific 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
Query!
Secondary ID [1]
0
0
2017-004135-36
Query!
Secondary ID [2]
0
0
WTX101-301
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Wilson Disease
0
0
Query!
Condition category
Condition code
Oral and Gastrointestinal
0
0
0
0
Query!
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Query!
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Human Genetics and Inherited Disorders
0
0
0
0
Query!
Other human genetics and inherited disorders
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - ALXN1840
Treatment: Drugs - SoC Therapy
Experimental: ALXN1840 - 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.
Active Comparator: Standard of Care (SoC) Medication - 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.
Treatment: Drugs: ALXN1840
ALXN1840 administered orally in 15 mg tablets
Treatment: Drugs: SoC Therapy
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
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)
Query!
Assessment method [1]
0
0
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).
Query!
Timepoint [1]
0
0
Baseline to Week 48
Query!
Secondary outcome [1]
0
0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Baseline up to Week 48
Query!
Secondary outcome [2]
0
0
Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
Query!
Assessment method [2]
0
0
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of Wilson Disease (WD). 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 may be reported to a non-blinded member of the study team, by the participant, family member or caregiver. 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.
Query!
Timepoint [2]
0
0
Baseline, Week 48
Query!
Secondary outcome [3]
0
0
Change From Baseline in UWDRS Part III Total Score at Week 48
Query!
Assessment method [3]
0
0
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of Wilson Disease (WD). 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.
Query!
Timepoint [3]
0
0
Baseline, Week 48
Query!
Secondary outcome [4]
0
0
Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
Baseline, Week 48
Query!
Secondary outcome [5]
0
0
Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48
Query!
Assessment method [5]
0
0
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).
Query!
Timepoint [5]
0
0
Baseline, Week 48
Query!
Secondary outcome [6]
0
0
Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
Week 48
Query!
Secondary outcome [7]
0
0
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
Baseline, Week 48
Query!
Secondary outcome [8]
0
0
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
Query!
Assessment method [8]
0
0
The MELD is a scoring system for assessing the severity of chronic liver disease in participants 12 years and older. 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.
Query!
Timepoint [8]
0
0
Baseline, Week 48
Query!
Secondary outcome [9]
0
0
Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48
Query!
Assessment method [9]
0
0
cNCC [µmol/L] = Plasma Total Copper (Cu) [micrograms (µg)/L]-(3.15*ceruloplasmin [milligrams (mg)/L])/63.5 [µg/µmol]
For ALXN1840-treated participants, cNCC in plasma was corrected for the amount of Cu bound to ALXN1840 tripartite complex (TPC) using square root-based cNCC correction method (cNCCcorrected):
cNCCcorrected = (vcNCC- 0.993)2vMo, (Mo= molybdenum).
In calculation of cNCC and cNCCcorrected following rules apply:
For plasma total Cu concentration values <lower limit of quantification (LLOQ), cNCC was considered missing (LLOQ value of plasma total Cu= 20 nanograms [ng]/mL);
Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ value of serum ceruloplasmin= 22.5 mg/L);
Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ value of plasma total Mo= 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 0.993vMo > vcNCC.
Query!
Timepoint [9]
0
0
Baseline, Week 48
Query!
Secondary outcome [10]
0
0
Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
Query!
Assessment method [10]
0
0
cNCC was calculated as follows: cNCC [µmol/L] = Plasma Total Cu [µg/L]-(3.15*ceruloplasmin [mg/L])/63.5 [µg/µmol]
For ALXN1840-treated participants, the cNCC in plasma was corrected for the amount of Cu bound to the ALXN1840 TPC using the square root-based cNCC correction method (cNCCcorrected) as follows:
cNCCcorrected = (vcNCC- 0.993)2vMo, where Mo = molybdenum.
In the calculation of cNCC and cNCCcorrected the following rules apply:
For plasma total Cu concentration values < LLOQ, cNCC was considered missing (LLOQ value of plasma total Cu = 20 ng/mL);
Serum ceruloplasmin concentration values <LLOQ are set to 0 (LLOQ value of serum ceruloplasmin = 22.5 mg/L);
Plasma total Mo concentration values <LLOQ are set to 0 (LLOQ value of plasma total Mo = 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 0.993vMo > vcNCC.
Query!
Timepoint [10]
0
0
Baseline, Week 48
Query!
Secondary outcome [11]
0
0
cNCC/cNCCcorrected Responder at Week 48
Query!
Assessment method [11]
0
0
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.
Query!
Timepoint [11]
0
0
Week 48
Query!
Eligibility
Key inclusion criteria
Key
- 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
Query!
Minimum age
12
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people assessing the outcomes
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
15/02/2018
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
30/06/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
214
Query!
Recruitment in Australia
Recruitment state(s)
NSW,SA
Query!
Recruitment hospital [1]
0
0
Clinical Trial Site - Concord
Query!
Recruitment hospital [2]
0
0
Clinical Trial Site - Adelaide
Query!
Recruitment postcode(s) [1]
0
0
2139 - Concord
Query!
Recruitment postcode(s) [2]
0
0
5000 - Adelaide
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Connecticut
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Illinois
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Michigan
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Texas
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Washington
Query!
Country [7]
0
0
Austria
Query!
State/province [7]
0
0
Styria
Query!
Country [8]
0
0
Austria
Query!
State/province [8]
0
0
Tyrol
Query!
Country [9]
0
0
Austria
Query!
State/province [9]
0
0
Vienna
Query!
Country [10]
0
0
Canada
Query!
State/province [10]
0
0
Ontario
Query!
Country [11]
0
0
Czechia
Query!
State/province [11]
0
0
Prague
Query!
Country [12]
0
0
Denmark
Query!
State/province [12]
0
0
Aarhus
Query!
Country [13]
0
0
France
Query!
State/province [13]
0
0
Bron
Query!
Country [14]
0
0
France
Query!
State/province [14]
0
0
Paris
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Sachsen
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Hamburg
Query!
Country [17]
0
0
Germany
Query!
State/province [17]
0
0
Heidelberg
Query!
Country [18]
0
0
Hong Kong
Query!
State/province [18]
0
0
Hong Kong
Query!
Country [19]
0
0
Hungary
Query!
State/province [19]
0
0
Budapest
Query!
Country [20]
0
0
Israel
Query!
State/province [20]
0
0
Jerusalem
Query!
Country [21]
0
0
Israel
Query!
State/province [21]
0
0
Tel-Hashomer
Query!
Country [22]
0
0
Japan
Query!
State/province [22]
0
0
Chiba
Query!
Country [23]
0
0
Japan
Query!
State/province [23]
0
0
Ehime
Query!
Country [24]
0
0
Japan
Query!
State/province [24]
0
0
Fukuoka
Query!
Country [25]
0
0
Japan
Query!
State/province [25]
0
0
Hokkaido
Query!
Country [26]
0
0
Japan
Query!
State/province [26]
0
0
Kanagawa
Query!
Country [27]
0
0
Japan
Query!
State/province [27]
0
0
Osaka
Query!
Country [28]
0
0
Japan
Query!
State/province [28]
0
0
Tokyo
Query!
Country [29]
0
0
Korea, Republic of
Query!
State/province [29]
0
0
Daegu
Query!
Country [30]
0
0
New Zealand
Query!
State/province [30]
0
0
Auckland
Query!
Country [31]
0
0
Poland
Query!
State/province [31]
0
0
Woj. Mazowieckie
Query!
Country [32]
0
0
Poland
Query!
State/province [32]
0
0
Warszawa
Query!
Country [33]
0
0
Russian Federation
Query!
State/province [33]
0
0
Moscow
Query!
Country [34]
0
0
Russian Federation
Query!
State/province [34]
0
0
Nizhny Novgorod
Query!
Country [35]
0
0
Russian Federation
Query!
State/province [35]
0
0
Saint Petersburg
Query!
Country [36]
0
0
Serbia
Query!
State/province [36]
0
0
Belgrade
Query!
Country [37]
0
0
Singapore
Query!
State/province [37]
0
0
Singapore
Query!
Country [38]
0
0
Spain
Query!
State/province [38]
0
0
Barcelona
Query!
Country [39]
0
0
Spain
Query!
State/province [39]
0
0
Málaga
Query!
Country [40]
0
0
Taiwan
Query!
State/province [40]
0
0
Taoyuan City
Query!
Country [41]
0
0
Turkey
Query!
State/province [41]
0
0
Istanbul
Query!
Country [42]
0
0
Turkey
Query!
State/province [42]
0
0
Izmir
Query!
Country [43]
0
0
United Kingdom
Query!
State/province [43]
0
0
England
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Alexion Pharmaceuticals, Inc.
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03403205
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Eugene S. Swenson, M.D., Ph.D.
Query!
Address
0
0
Alexion Pharmaceuticals, Inc.
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03403205
Download to PDF