A Phase 2 interventional study of Bis-Choline Tetrathiomolybdate in Wilson Disease, sponsored by Alexion Pharmaceuticals, Inc.. Completed at 12 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-18.
Sponsored by Alexion Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
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.
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.
78 studies on the registry are indexed under Hepatolenticular Degeneration; 30 are open to participants now.
This study's enrollment of 31 is close to the median of 30 across 42 interventional studies indexed under Hepatolenticular Degeneration.
Browse Hepatolenticular Degeneration studies →Alexion Pharmaceuticals, Inc. is the lead sponsor of 249 studies on the registry; 25 are open to participants now.
Of its 98 completed or terminated interventional studies of FDA-regulated products, 70 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will receive ALXN1840.
Drug: 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.
Also known as: ALXN1840
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
| Milestone | ALXN1840 |
|---|---|
| Started | 31 |
| Received at least 1 dose of study drug | 31 |
| Completed | 26 |
| Not completed | 5 |
| Withdrew: Adverse event | 3 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Other than specified | 1 |
| Milestone | ALXN1840 |
|---|---|
| Started | 25 |
| Received at least 1 dose of study drug | 25 |
| Completed | 21 |
| Not completed | 4 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Other than specified | 2 |
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.
| μg/g | ALXN1840 |
|---|---|
| Change From Baseline in Liver Cu Concentration at Week 48 (Treatment Period) | 92.8 ± 56.34 |
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.
| Participants | ALXN1840 |
|---|---|
| Baseline — Score 0 | 7 |
| Baseline — Score 1a | 1 |
| Baseline — Score 1b | 0 |
| Baseline — Score 1c | 7 |
| Baseline — Score 2 | 3 |
| Baseline — Score 3 | 8 |
| Baseline — Score 4 | 2 |
| Baseline — Not evaluable | 1 |
| Week 48 — Score 0 | 5 |
| Week 48 — Score 1a | 0 |
| Week 48 — Score 1b | 0 |
| Week 48 — Score 1c | 6 |
| Week 48 — Score 2 | 6 |
| Week 48 — Score 3 | 7 |
| Week 48 — Score 4 | 0 |
| Week 48 — Not evaluable | 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.
| Participants | ALXN1840 |
|---|---|
| Baseline — Score 0 | 8 |
| Baseline — Score 1 | 7 |
| Baseline — Score 2 | 4 |
| Baseline — Score 3 | 7 |
| Baseline — Score 4 | 2 |
| Baseline — Not evaluable | 1 |
| Week 48 — Score 0 | 5 |
| Week 48 — Score 1 | 4 |
| Week 48 — Score 2 | 8 |
| Week 48 — Score 3 | 7 |
| Week 48 — Score 4 | 0 |
| Week 48 — Not evaluable | 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.
| Participants | ALXN1840 |
|---|---|
| Baseline — Score 0 | 8 |
| Baseline — Score 1 | 6 |
| Baseline — Score 2 | 2 |
| Baseline — Score 3 | 9 |
| Baseline — Score 4 | 1 |
| Baseline — Score 5 | 1 |
| Baseline — Score 6 | 1 |
| Baseline — Not evaluable | 1 |
| Week 48 — Score 0 | 5 |
| Week 48 — Score 1 | 4 |
| Week 48 — Score 2 | 4 |
| Week 48 — Score 3 | 8 |
| Week 48 — Score 4 | 3 |
| Week 48 — Score 5 | 0 |
| Week 48 — Score 6 | 0 |
| Week 48 — Not evaluable | 0 |
Fibrosis from histology was evaluated by morphometric quantification of hepatic collagen content.
| percentage of collagen | ALXN1840 |
|---|---|
| Change From Baseline in Hepatic Collagen Content at Week 48 (Treatment Period) | 8.5445 ± 15.54224 |
Fibrosis from histology was evaluated by morphometric quantification of hepatic a-SMA content.
| percentage of a-SMA | ALXN1840 |
|---|---|
| Change From Baseline in a-SMA Content at Week 48 (Treatment Period) | 1.6002 ± 5.47274 |
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.
| Participants | ALXN1840 |
|---|---|
| Baseline — Score 0 | 19 |
| Baseline — Score 1 | 6 |
| Baseline — Score 2 | 3 |
| Baseline — Score 3 | 1 |
| Week 48 — Score 0 | 15 |
| Week 48 — Score 1 | 6 |
| Week 48 — Score 2 | 2 |
| Week 48 — Score 3 | 1 |
Steatosis from histology was evaluated by morphometric quantification of hepatic fat content.
| percentage of fat | ALXN1840 |
|---|---|
| Change From Baseline in Hepatic Fat Content at Week 48 (Treatment Period) | -0.2504 ± 2.19263 |
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.
| units on a scale | ALXN1840 |
|---|---|
| Change From Baseline in NAS Total Score at Week 48 (Treatment Period) | 0.1 ± 1.69 |
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.
| Participants | ALXN1840 |
|---|---|
| Treatment Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 30 |
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.
| Participants | ALXN1840 |
|---|---|
| Extension Period: Number of Participants With TEAEs | 24 |
| nanograms (ng)/milliliter (mL) | ALXN1840 |
|---|---|
| Week 6 | 174.39 ± 113.824 |
| Week 36 | 131.19 ± 103.359 |
| ng/mL | ALXN1840 |
|---|---|
| Week 6 | 5.888 ± 2.0176 |
| Week 36 | 7.843 ± 6.0564 |
| μg/g | ALXN1840 |
|---|---|
| Change From Baseline in Mo in Liver Biopsy Specimen at Week 48 (Treatment Period) | 69.6976 ± 43.02655 |
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.
| units on a scale | ALXN1840 |
|---|---|
| Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 48 (Treatment Period) | 3.1 ± 1.26 |
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.
| units on a scale | ALXN1840 |
|---|---|
| Change From Baseline in CGI-S Scale Score at Week 48 (Treatment Period) | -0.4 ± 1.50 |
Collected over Day 1 (Treatment Period) up to Week 52 (Extension Period) (up to a total of approximately 100 weeks). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Period: ALXN1840 | 0/31 (0%) | 3/31 (9.7%) | 30/31 (96.8%) |
| Extension Period: ALXN1840 | 0/25 (0%) | 2/25 (8%) | 24/25 (96%) |
| Event | Treatment Period: ALXN1840 | Extension Period: ALXN1840 |
|---|---|---|
| Suicidal ideationPsychiatric disorders | 0/31 | 1/25 |
| Humerus fractureInjury, poisoning and procedural complications | 0/31 | 1/25 |
| Drug-induced liver injuryHepatobiliary disorders | 1/31 | 0/25 |
| Hepatic enzyme increasedInvestigations | 1/31 | 0/25 |
| Bence Jones proteinuriaRenal and urinary disorders | 1/31 | 0/25 |
| Ureteric obstructionRenal and urinary disorders | 1/31 | 0/25 |
| ProstatitisReproductive system and breast disorders | 1/31 | 0/25 |
| Event | Treatment Period: ALXN1840 | Extension Period: ALXN1840 |
|---|---|---|
| COVID-19Infections and infestations | 4/31 | 10/25 |
| NasopharyngitisInfections and infestations | 5/31 | 8/25 |
| Alanine aminotransferase increasedInvestigations | 8/31 | 8/25 |
| Gamma-glutamyltransferase increasedInvestigations | 8/31 | 7/25 |
| NauseaGastrointestinal disorders | 6/31 | 6/25 |
| HeadacheNervous system disorders | 7/31 | 6/25 |
| Heavy menstrual bleedingReproductive system and breast disorders | 1/11 | 2/9 |
| PyrexiaGeneral disorders | 5/31 | 3/25 |
| Upper respiratory tract infectionInfections and infestations | 2/31 | 4/25 |
| Blood alkaline phosphatase increasedInvestigations | 4/31 | 4/25 |
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 copper (Cu) value evaluable.
| Age, Continuous(years) | ALXN1840 |
|---|---|
| Mean | 37.9 ± 13.81 |
| Sex: Female, Male(Participants) | ALXN1840 |
|---|---|
| Female | 10 |
| Male | 19 |
| Ethnicity (NIH/OMB)(Participants) | ALXN1840 |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 23 |
| Unknown or Not Reported | 4 |
| Race/Ethnicity, Customized(Participants) | ALXN1840 |
|---|---|
| Race — White | 19 |
| Race — Asian | 6 |
| Race — Other | 3 |
| Race — Unknown | 1 |
| Liver Cu Concentration(micrograms (μg)/gram (g)) | ALXN1840 |
|---|---|
| Mean | 511.2 ± 361.85 |
| Hepatic Collagen Content(percentage of collagen) | ALXN1840 |
|---|---|
| Mean | 10.2993 ± 6.81501 |
| Alpha-Smooth Muscle Actin (a-SMA) Content(percentage of a-SMA) | ALXN1840 |
|---|---|
| Mean | 5.3134 ± 3.25982 |
| Hepatic Fat Content(percentage of fat) | ALXN1840 |
|---|---|
| Mean | 1.5815 ± 2.60491 |
3 further baseline measures are reported on the registry.
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Hepatolenticular Degeneration→
Alexion Pharmaceuticals, Inc.