Wilson DiseasePhase 2NCT04422431
Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840
A Phase 2 study testing Bis-Choline Tetrathiomolybdate in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 12 sites in 8 countries.
Trial summary
The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Wilson Disease
- What is being tested?
- Bis-Choline Tetrathiomolybdate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 12 sitesin 8 countries
- Study dates
- 2 Dec 2020to 17 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.
- Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
- Body mass index < 30 kilograms/meter squared.
- Able to cooperate with a percutaneous liver biopsy.
- Willing and able to follow protocol-specified contraception requirements.
- Capable of giving signed informed consent.
Who cannot join
- Decompensated cirrhosis or Model for End Stage Liver Disease score > 13.
- Modified Nazer score > 7.
- Clinically significant gastrointestinal bleed within past 3 months.
- Alanine aminotransferase > 2 × upper limit of normal.
- History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time ≥ 1.5.
- Participant unwilling to accept blood products, if required.
Show all 11Show fewer
- Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
- Hemoglobin less than lower limit of the reference range for age and sex.
- Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute.
- Lymphoma, leukemia, or any malignancy within the past 5 years.
- Current or chronic history of liver disease not associated with WD.
Trial locations and contacts
12 sites in 8 countries.
12 sites in 8 countries
United States3 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Dallas, Texas, 75235
Research Site
Sacramento, California, 95817
Russia2 sites
Research Site
Moscow, 119021
Research Site
Saint Petersburg, 194017
About this study
Official 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
The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). In the Treatment Period, efficacy and safety of ALXN1840 will be assessed at Week 48.
Read the detailed description
Participants who complete the 48-week Treatment Period will be offered the opportunity to continue their treatment in a 48-week Extension Period that will offer additional time for evaluation of long-term efficacy and safety of ALXN1840. There will be no liver biopsies during the Extension Period.
- Conditions
- Wilson Disease
- Being tested
- Bis-Choline Tetrathiomolybdate
- Keywords
- Copper, ALXN1840, Histology, Liver Biopsy
- Medical subject headings
- Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bis-Choline TetrathiomolybdateDrug
Also called ALXN1840
Participants will be initiated at 15 milligrams once daily, then the dose will be increased to 30 milligrams once daily at Week 6.
| Study group | Role | What they receive |
|---|---|---|
| ALXN1840 | Experimental | Participants will receive ALXN1840. Receives: Drug: Bis-Choline Tetrathiomolybdate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Secondary outcomes (15)
Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)
Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content.
Measured: Baseline, Week 48 (Treatment Period)
Change From Baseline in a-SMA Content at Week 48 (Treatment Period)
Fibrosis from histology was evaluated by morphometric quantification of hepatic a-SMA content.
Measured: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)
Steatosis from histology was evaluated by morphometric quantification of hepatic fat content.
Measured: Baseline, Week 48 (Treatment Period)
Change From Baseline in NAS Total Score at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Measured: Day 1 (Treatment Period) up to Week 48 (Treatment Period)
Extension Period: Number of Participants With TEAEs
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.
Measured: Day 1 (Extension Period) up Week 52 (Extension Period)
Treatment Period: Predose Trough Plasma Total Mo Concentration
Measured: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Treatment Period: Predose Trough Plasma Total PUF Mo Concentration
Measured: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)
Measured: Baseline, Week 48 (Treatment Period)
Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)
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.
Measured: Week 48 (Treatment Period)
Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)
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.
Measured: Baseline, Week 48 (Treatment Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start2 Dec 2020
- Primary completion21 May 2022
- Study completion17 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Wilson DiseaseStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eugene S. Swenson, MD, PhD, Study director, Alexion Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04422431
- Sponsor's protocol ID
- ALXN1840-WD-205
- Other IDs
- 2019-003711-60, 2019
- Status last verified
- Oct 2024
- First submitted
- 22 May 2020
- Last updated
- 18 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04422431
- Acronym / sponsor ID
- ALXN1840-WD-205
- Conditions
- Wilson Disease
- Keywords
- Copper, ALXN1840, Histology, Liver Biopsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 Dec 2020 (actual)
- Primary completion
- 21 May 2022 (actual)
- Study completion
- 17 May 2023 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the study is to evaluate the change in liver copper (Cu) concentration following 48 weeks of treatment with ALXN1840 in adult participants with Wilson Disease (WD) who have been previously treated for at least 1 year with standard of care (that is, trientine, penicillamine, or zinc). In the Treatment Period, efficacy and safety of ALXN1840 will be assessed at Week 48.
Detailed description
Participants who complete the 48-week Treatment Period will be offered the opportunity to continue their treatment in a 48-week Extension Period that will offer additional time for evaluation of long-term efficacy and safety of ALXN1840. There will be no liver biopsies during the Extension Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALXN1840 | Experimental | Drug: Bis-Choline TetrathiomolybdateParticipants will receive ALXN1840. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.
- Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.
- Body mass index < 30 kilograms/meter squared.
- Able to cooperate with a percutaneous liver biopsy.
- Willing and able to follow protocol-specified contraception requirements.
Key exclusion criteria (11 listed)
- Decompensated cirrhosis or Model for End Stage Liver Disease score > 13.
- Modified Nazer score > 7.
- Clinically significant gastrointestinal bleed within past 3 months.
- Alanine aminotransferase > 2 × upper limit of normal.
- History of bleeding abnormality or known coagulopathy, including platelet count < 100,000, and international normalized ratio for prothrombin time ≥ 1.5.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bis-Choline TetrathiomolybdateAlso: ALXN1840Participants will be initiated at 15 milligrams once daily, then the dose will be increased to 30 milligrams once daily at Week 6. | Drug | ALXN1840 |
Primary outcome
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
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.
15 secondary outcomes
Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Change From Baseline in a-SMA Content at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Change From Baseline in NAS Total Score at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 (Treatment Period) up to Week 48 (Treatment Period)
Extension Period: Number of Participants With TEAEs
Time frame: Day 1 (Extension Period) up Week 52 (Extension Period)
Treatment Period: Predose Trough Plasma Total Mo Concentration
Time frame: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Treatment Period: Predose Trough Plasma Total PUF Mo Concentration
Time frame: Predose up to 4 hours postdose at Week 6 (Day 43) and Week 36 (Day 253)
Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period)
Time frame: Week 48 (Treatment Period)
Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene S. Swenson, MD, PhD study director
Alexion Pharmaceuticals, Inc.
12 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bis-Choline Tetrathiomolybdate in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 12 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Russia, Spain, Canada, Denmark and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) (time frame: Baseline, Week 48 (Treatment Period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2024.