Wilson Disease
Conditions
Keywords
Copper, ALXN1840, Histology, Liver Biopsy
Brief 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). 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.
Interventions
DRUGBis-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.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is only pathologist-blinded for the assessments of liver histology samples.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline, 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. |
| Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline, 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. |
| Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period) | Baseline, Week 48 (Treatment Period) | Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content. |
| Change From Baseline in a-SMA Content at Week 48 (Treatment Period) | Baseline, Week 48 (Treatment Period) | Fibrosis from histology was evaluated by morphometric quantification of hepatic a-SMA content. |
| Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Baseline, 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. |
| Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period) | Baseline, Week 48 (Treatment Period) | Steatosis from histology was evaluated by morphometric quantification of hepatic fat content. |
| Change From Baseline in NAS Total Score at Week 48 (Treatment Period) | Baseline, 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. |
| Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline, 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. |
| Extension Period: Number of Participants With TEAEs | Day 1 (Extension Period) up Week 52 (Extension Period) | 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. |
| Treatment Period: Predose Trough Plasma Total Mo Concentration | 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 | 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) | Baseline, Week 48 (Treatment Period) | — |
| Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period) | 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. |
| Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period) | Baseline, 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. |
| Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 (Treatment Period) up to Week 48 (Treatment Period) | 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. |
Countries
Canada, Denmark, New Zealand, Russia, Singapore, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALXN1840 Participants received ALXN1840 orally in the 48-week Treatment Period. Participants who completed the 48-week Treatment Period and agreed to enter a 48-week Extension Period, continued to receive ALXN1840. Participants who did not enter the Extension Period discontinued dosing at Week 48, and had a final study visit for safety follow-up at Week 52. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Period (48 Weeks) | Lost to Follow-up | 1 |
| Extension Period (48 Weeks) | Other than specified | 2 |
| Extension Period (48 Weeks) | Withdrawal by Subject | 1 |
| Treatment Period (48 Weeks) | Adverse Event | 3 |
| Treatment Period (48 Weeks) | Other than specified | 1 |
| Treatment Period (48 Weeks) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | ALXN1840 |
|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 13.81 |
| Alpha-Smooth Muscle Actin (a-SMA) Content | 5.3134 percentage of a-SMA STANDARD_DEVIATION 3.25982 |
| Clinical Global Impression-Severity (CGI-S) Scale Score | 2.3 units on a scale STANDARD_DEVIATION 1.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Hepatic Collagen Content | 10.2993 percentage of collagen STANDARD_DEVIATION 6.81501 |
| Hepatic Fat Content | 1.5815 percentage of fat STANDARD_DEVIATION 2.60491 |
| Liver Cu Concentration | 511.2 micrograms (μg)/gram (g) STANDARD_DEVIATION 361.85 |
| Molybdenum (Mo) in Liver Biopsy Specimen | 4.1591 μg/g STANDARD_DEVIATION 4.43552 |
| Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Total Score | 1.2 units on a scale STANDARD_DEVIATION 1.45 |
| Race/Ethnicity, Customized Race Asian | 6 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants |
| Race/Ethnicity, Customized Race White | 19 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 25 |
| other Total, other adverse events | 30 / 31 | 24 / 25 |
| serious Total, serious adverse events | 3 / 31 | 2 / 25 |
Outcome results
Primary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) | 92.8 μg/g | Standard Error 56.34 |
p-value: 0.1002t-test, 2 sided
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in a-SMA Content at Week 48 (Treatment Period) | 1.6002 percentage of a-SMA | Standard Deviation 5.47274 |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period) | -0.4 units on a scale | Standard Deviation 1.5 |
Secondary
Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period)
Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period) | 8.5445 percentage of collagen | Standard Deviation 15.54224 |
Secondary
Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period)
Steatosis from histology was evaluated by morphometric quantification of hepatic fat content.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period) | -0.2504 percentage of fat | Standard Deviation 2.19263 |
Secondary
Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period)
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period) | 69.6976 μg/g | Standard Deviation 43.02655 |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Change From Baseline in NAS Total Score at Week 48 (Treatment Period) | 0.1 units on a scale | Standard Deviation 1.69 |
Secondary
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.
Time frame: Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 | Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period) | 3.1 units on a scale | Standard Deviation 1.26 |
Secondary
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.
Time frame: Day 1 (Extension Period) up Week 52 (Extension Period)
Population: Safety Analysis Set in the Extension Period included all participants who received at least 1 dose of ALXN1840 in the Extension Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1840 | Extension Period: Number of Participants With TEAEs | 24 Participants |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 0 | 8 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 1 | 6 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 2 | 2 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 3 | 9 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 4 | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 5 | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 6 | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Baseline | Not evaluable | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 0 | 5 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 1 | 4 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 2 | 4 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 3 | 8 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 4 | 3 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 5 | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 6 | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Ishak Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Not evaluable | 0 Participants |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 0 | 8 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 1 | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 2 | 4 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 3 | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Score 4 | 2 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Baseline | Not evaluable | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 0 | 5 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 1 | 4 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 2 | 8 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 3 | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Score 4 | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Metavir Fibrosis Score at Week 48 (Treatment Period) | Week 48 | Not evaluable | 0 Participants |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Baseline | Score 1 | 6 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Baseline | Score 2 | 3 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Baseline | Score 0 | 19 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Baseline | Score 3 | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Week 48 | Score 0 | 15 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Week 48 | Score 1 | 6 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Week 48 | Score 2 | 2 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in NAS Steatosis Grading Score at Week 48 (Treatment Period) | Week 48 | Score 3 | 1 Participants |
Secondary
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.
Time frame: Baseline, Week 48 (Treatment Period)
Population: The Full Analysis Set in the Treatment Period included all participants who received at least 1 dose of study drug in the Treatment Period and had at least a Baseline liver Cu value evaluable. 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 0 | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 1a | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 1b | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 1c | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 2 | 3 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 3 | 8 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Score 4 | 2 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Baseline | Not evaluable | 1 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 0 | 5 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 1a | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 1b | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 1c | 6 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 2 | 6 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 3 | 7 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Score 4 | 0 Participants |
| ALXN1840 | Number of Participants With Change From Baseline in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Stage at Week 48 (Treatment Period) | Week 48 | Not evaluable | 0 Participants |
Secondary
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.
Time frame: Day 1 (Treatment Period) up to Week 48 (Treatment Period)
Population: Safety Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1840 | Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 30 Participants |
Secondary
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)
Population: Pharmacokinetic (PK) Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period and had evaluable PK data for total Mo and/or plasma ultrafiltrate (PUF) Mo (as surrogate measure for ALXN1840 PK) in plasma in the Treatment Period. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1840 | Treatment Period: Predose Trough Plasma Total Mo Concentration | Week 6 | 174.39 nanograms (ng)/milliliter (mL) | Standard Deviation 113.824 |
| ALXN1840 | Treatment Period: Predose Trough Plasma Total Mo Concentration | Week 36 | 131.19 nanograms (ng)/milliliter (mL) | Standard Deviation 103.359 |
Secondary
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)
Population: PK Analysis Set in the Treatment Period included all participants who received at least 1 dose of treatment in the Treatment Period and had evaluable PK data for total Mo and/or PUF Mo (as surrogate measure for ALXN1840 PK) in plasma in the Treatment Period. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1840 | Treatment Period: Predose Trough Plasma Total PUF Mo Concentration | Week 6 | 5.888 ng/mL | Standard Deviation 2.0176 |
| ALXN1840 | Treatment Period: Predose Trough Plasma Total PUF Mo Concentration | Week 36 | 7.843 ng/mL | Standard Deviation 6.0564 |