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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04422431




Registration number
NCT04422431
Ethics application status
Date submitted
22/05/2020
Date registered
9/06/2020

Titles & IDs
Public title
Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
Scientific title
A Phase 2, Single-arm Pathologist-blinded 48-week Study Using Liver Biopsy Specimens to Assess Copper Concentration and Histopathologic Changes in ALXN1840-treated Patients With Wilson Disease Followed by an up to 48-weeks Extension Period
Secondary ID [1] 0 0
2019-003711-60
Secondary ID [2] 0 0
ALXN1840-WD-205
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 - Bis-Choline Tetrathiomolybdate

Experimental: ALXN1840 - Participants will receive ALXN1840.


Treatment: Drugs: Bis-Choline Tetrathiomolybdate
Participants will be initiated at 15 milligrams once daily, then the dose will be increased to 30 milligrams once daily at Week 6.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
Assessment method [1] 0 0
Liver biopsy samples were taken for the assessment of liver Cu concentration. Multiple imputation was used to impute missing data at Week 48 due to any reason based on Baseline values.
Timepoint [1] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [1] 0 0
Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)
Assessment method [1] 0 0
Fibrosis from histology was evaluated by NASH CRN Fibrosis Stage, which was scaled from 0 to 4 stages where Score 0: None; Score 1: Perisinusoidal or periportal - 1a - mild, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1b - moderate, zone 3, perisinusoidal; Score 1: Perisinusoidal or periportal - 1c - portal/periportal; Score 2: Both perisinusoidal and portal/periportal; Score 3: Bridging fibrosis; and Score 4: Cirrhosis. Higher scores indicated greater fibrosis.
Timepoint [1] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [2] 0 0
Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)
Assessment method [2] 0 0
Fibrosis from histology was evaluated by Metavir Fibrosis Score, which was ranged from 0 to 4 where Score 0: No fibrosis; Score 1: Stellate enlargement of portal tract but without septa formation; Score 2: Enlargement of portal tract with rare septa formation; Score 3: Numerous septa without cirrhosis; and Score 4: Cirrhosis. Higher scores indicated greater fibrosis.
Timepoint [2] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [3] 0 0
Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)
Assessment method [3] 0 0
Fibrosis from histology was evaluated by Ishak Fibrosis Score, which was ranged from 0 to 6 where Score 0: No fibrosis; Score 1: Fibrous expansion of some portal areas, with or without short fibrous septa; Score 2: Fibrous expansion of most portal areas, with or without short fibrous septa; Score 3: Fibrous expansion of most portal areas with occasional portal to portal (P-P) bridging; and Score 4: Fibrous expansion of portal areas with marked bridging (P-P) as well as portal central (P-C); Score 5: Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); and Score 6: Cirrhosis, probable or definite. Higher scores indicated greater fibrosis.
Timepoint [3] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [4] 0 0
Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)
Assessment method [4] 0 0
Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content.
Timepoint [4] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [5] 0 0
Change From Baseline in a-SMA Content at Week 48 (Treatment Period)
Assessment method [5] 0 0
Fibrosis from histology was evaluated by morphometric quantification of hepatic a-SMA content.
Timepoint [5] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [6] 0 0
Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)
Assessment method [6] 0 0
Steatosis from histology was evaluated by the steatosis component of the NAS, which was ranged from 0 to 3 where Score 0: \< 5% (minimal); Score 1: 5 - 33% (mild); Score 2: 34 - 66% (moderate); and Score 3: \> 66% (severe). Higher scores indicated greater steatosis.
Timepoint [6] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [7] 0 0
Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)
Assessment method [7] 0 0
Steatosis from histology was evaluated by morphometric quantification of hepatic fat content.
Timepoint [7] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [8] 0 0
Change From Baseline in NAS Total Score at Week 48 (Treatment Period)
Assessment method [8] 0 0
Inflammation was quantified by the NAS total score. The score is defined as the unweighted sum of the scores for steatosis (0 \[minimal\] to 3 \[severe\]), lobular inflammation (0 \[none\] to 3 \[\>4 foci / 200x field\]), and hepatocellular ballooning (0 \[none\] to 2 \[many\]), thus ranging from 0 (no inflammation) to 8 (severe inflammation), with higher scores indicating more severe disease.
Timepoint [8] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [9] 0 0
Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Assessment method [9] 0 0
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The TEAEs were AEs with onset on or after the first study drug dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Timepoint [9] 0 0
Day 1 (Treatment Period) up to Week 48 (Treatment Period)
Secondary outcome [10] 0 0
Extension Period: Number of Participants With TEAEs
Assessment method [10] 0 0
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The TEAEs were AEs with onset on or after the first study drug dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Timepoint [10] 0 0
Day 1 (Extension Period) up Week 52 (Extension Period)
Secondary outcome [11] 0 0
Treatment Period: Predose Trough Plasma Total Mo Concentration
Assessment method [11] 0 0
Timepoint [11] 0 0
Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Secondary outcome [12] 0 0
Treatment Period: Predose Trough Plasma Total PUF Mo Concentration
Assessment method [12] 0 0
Timepoint [12] 0 0
Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Secondary outcome [13] 0 0
Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)
Assessment method [13] 0 0
Timepoint [13] 0 0
Baseline, Week 48 (Treatment Period)
Secondary outcome [14] 0 0
Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)
Assessment method [14] 0 0
The CGI-I is a 7-point scale clinician assessment where 1= very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. Higher scores indicated worsening of disease.
Timepoint [14] 0 0
Week 48 (Treatment Period)
Secondary outcome [15] 0 0
Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)
Assessment method [15] 0 0
The CGI-S is a 7-point scale clinician assessment. Participants were assessed on severity of illness at the time of rating/assessment as follows: 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. Higher scores indicated worsening of disease.
Timepoint [15] 0 0
Baseline, Week 48 (Treatment Period)

Eligibility
Key inclusion criteria
1. Diagnosis of WD by Leipzig Criteria = 4 or by historical test results.
2. Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
3. Body mass index < 30 kilograms/meter squared.
4. Able to cooperate with a percutaneous liver biopsy.
5. Willing and able to follow protocol-specified contraception requirements.
6. Capable of giving signed informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Decompensated cirrhosis or Model for End Stage Liver Disease score > 13.
2. Modified Nazer score > 7.
3. Clinically significant gastrointestinal bleed within past 3 months.
4. Alanine aminotransferase > 2 × upper limit of normal.
5. History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time = 1.5.
6. Participant unwilling to accept blood products, if required.
7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
8. Hemoglobin less than lower limit of the reference range for age and sex.
9. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute.
10. Lymphoma, leukemia, or any malignancy within the past 5 years.
11. Current or chronic history of liver disease not associated with WD.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/05/2023
Sample size
Target
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Denmark
State/province [5] 0 0
Århus N
Country [6] 0 0
New Zealand
State/province [6] 0 0
Grafton
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Moscow
Country [8] 0 0
Russian Federation
State/province [8] 0 0
St. Petersburg
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Valencia
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Eugene S. Swenson, MD, PhD
Address 0 0
Alexion Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04422431