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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03403205




Registration number
NCT03403205
Ethics application status
Date submitted
19/12/2017
Date registered
18/01/2018

Titles & IDs
Public title
Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
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, With an Extension Period of up to 60 Months
Secondary ID [1] 0 0
2017-004135-36
Secondary ID [2] 0 0
WTX101-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Wilson Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

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)
Timepoint [1] 0 0
Baseline to Week 48
Secondary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Baseline up to Week 48
Secondary outcome [2] 0 0
Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
Timepoint [2] 0 0
Baseline, Week 48
Secondary outcome [3] 0 0
Change From Baseline in UWDRS Part III Total Score at Week 48
Timepoint [3] 0 0
Baseline, Week 48
Secondary outcome [4] 0 0
Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
Timepoint [4] 0 0
Baseline, Week 48
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
Timepoint [5] 0 0
Baseline, Week 48
Secondary outcome [6] 0 0
Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
Timepoint [6] 0 0
Week 48
Secondary outcome [7] 0 0
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
Timepoint [7] 0 0
Baseline, Week 48
Secondary outcome [8] 0 0
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
Timepoint [8] 0 0
Baseline, Week 48
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
Timepoint [9] 0 0
Baseline, Week 48
Secondary outcome [10] 0 0
Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
Timepoint [10] 0 0
Baseline, Week 48
Secondary outcome [11] 0 0
cNCC/cNCCcorrected Responder at Week 48
Timepoint [11] 0 0
Week 48

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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2023
Sample size
Target
Accrual to date
Final
214
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Concord
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
VIC 3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Austria
State/province [7] 0 0
Graz
Country [8] 0 0
Austria
State/province [8] 0 0
Innsbruck
Country [9] 0 0
Austria
State/province [9] 0 0
Vienna
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha 2
Country [12] 0 0
Denmark
State/province [12] 0 0
Århus N
Country [13] 0 0
France
State/province [13] 0 0
Bron
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Germany
State/province [15] 0 0
Hamburg
Country [16] 0 0
Germany
State/province [16] 0 0
Heidelberg
Country [17] 0 0
Germany
State/province [17] 0 0
Leipzig
Country [18] 0 0
Hong Kong
State/province [18] 0 0
Hong Kong
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Japan
State/province [22] 0 0
Chiba
Country [23] 0 0
Japan
State/province [23] 0 0
Kumamoto-shi
Country [24] 0 0
Japan
State/province [24] 0 0
Kurume-shi
Country [25] 0 0
Japan
State/province [25] 0 0
Matsuyama-city
Country [26] 0 0
Japan
State/province [26] 0 0
Meguro-ku
Country [27] 0 0
Japan
State/province [27] 0 0
Sapporo-shi
Country [28] 0 0
Japan
State/province [28] 0 0
Takatsuki-shi
Country [29] 0 0
Japan
State/province [29] 0 0
Yokohama-shi
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Daegu
Country [31] 0 0
New Zealand
State/province [31] 0 0
Grafton
Country [32] 0 0
Poland
State/province [32] 0 0
Warsaw
Country [33] 0 0
Poland
State/province [33] 0 0
Warszawa
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Moscow
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Nizhniy Novgorod
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
Serbia
State/province [37] 0 0
Belgrade
Country [38] 0 0
Singapore
State/province [38] 0 0
Singapore
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Málaga
Country [41] 0 0
Spain
State/province [41] 0 0
Sabadell
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taoyuan City
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Istanbul
Country [46] 0 0
Turkey
State/province [46] 0 0
Izmir
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Edgbaston
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Guildford
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eugene S. Swenson, M.D., Ph.D.
Address 0 0
Alexion Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03403205