A Phase 3 interventional study of ALXN1840 and SoC Therapy in Wilson Disease, sponsored by Alexion Pharmaceuticals, Inc.. Terminated at 56 sites in 22 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2024-06-17.
Sponsored by Alexion Pharmaceuticals, Inc. (part of AstraZeneca) · Phase 3, Interventional, and Treatment
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Among 10 studies testing tetrathiomolybdate in Hepatolenticular Degeneration — none open to participants now, none under way, none of them phase 3. tetrathiomolybdate · Hepatolenticular Degeneration.
Among the 10 studies testing tetrathiomolybdate in Hepatolenticular Degeneration, this one has the largest enrollment, is the only one that started in 2018, is one of 3 in phase 3, and was the 3rd registered.
80 studies on the registry are indexed under Hepatolenticular Degeneration; 31 are open to participants now.
Browse Hepatolenticular Degeneration studies →None of the 10 studies testing tetrathiomolybdate in Hepatolenticular Degeneration is open now. The open studies under Hepatolenticular Degeneration, anywhere →
No approval found in the FDA or EMA files read. How studies give it is on its page →
Of the 21 Hepatolenticular Degeneration studies recruiting now, 16 (76%) set no upper age limit and 4 (19%) stop at 75 or younger; 14 take children under 18; 3 take healthy volunteers.
This study: 12 Years and older · all sexes · no healthy volunteers.
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10 studies; the count open now beside each. This study's row is marked.
First in 1994; this study’s year is marked. 1 started in 2018.
This study's enrollment of 214 is above the median of 30 across 44 interventional studies indexed under Hepatolenticular Degeneration.
Median enrollment 38 across the 10 interventional studies. Of the 10 that completed or were terminated, 9 (90%) have results posted.
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9 of 10 have an industry lead sponsor. The 2 most frequent:
This study is registered under Alexion Pharmaceuticals, Inc., one of the names counted as AstraZeneca. Under that name alone:
Alexion Pharmaceuticals, Inc. is the lead sponsor of 255 studies on the registry; 23 are open to participants now.
Of its 101 completed or terminated interventional studies of FDA-regulated products, 75 (74%) have results posted.
11 studies in Hepatolenticular Degeneration by AstraZeneca: none open now, none under way, none of them phase 3. Of 10 finished, 10 (100%) have results posted.
Among the 11 studies in Hepatolenticular Degeneration by AstraZeneca, this one is the only one that started in 2018, is one of 2 in phase 3, and was the 3rd registered.
AstraZeneca’s Hepatolenticular Degeneration studies by the year they started, since 2014.
None of the studies under way reaches primary completion within a year.
Among the 10 studies testing tetrathiomolybdate in Hepatolenticular Degeneration, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among AstraZeneca’s 11 in Hepatolenticular Degeneration:
Nothing recorded among them since 2026-09-25.
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The study will evaluate the efficacy and safety of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson Disease (WD) participants aged 12 and older in the Primary Evaluation Period. In addition, efficacy and safety will be evaluated during an optional 60-month Extension Period.
The study consists of 2 cohorts. Cohort 1: Participants who have received SoC therapy for > 28 days and Cohort 2: Participants who are treatment-naïve or who have received SoC therapy for ≤ 28 days.
All enrolled participants were randomized by cohort in a 2:1 ratio to treatment with ALXN1840 or SoC (either as continued therapy in Cohort 1 or as continued or initial therapy in Cohort 2).
Key Inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALXN1840 was administered orally for 48 weeks at doses ranging from 15 milligrams (mg) every other day (QOD) up to a titrated dose of 60 mg daily. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.
Drug: ALXN1840
SoC medication was administered for 48 weeks. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.
Drug: SoC Therapy
ALXN1840 administered orally in 15 mg tablets
Also known as: Formerly named WTX101, Tiomolibdic acid, Tiomolibdate choline, Bis-choline tetrathiomolybdate
Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.
Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).
Time frame: Baseline to Week 48
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. TEAEs were defined as those AEs with onset after the first dose of randomized treatment or existing events that worsened in severity after the first dose of randomized treatment. 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: Baseline up to Week 48
Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items \[disability\], items 2 to 11 \[10 items in total\]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 \[23 items in total\]). The UWDRS Part II total score was calculated as the sum of Question 2 to Question 11 (each question has range 0 \[none\] to 4 \[severe\]). The UWDRS Part II total score ranges from 0 (no disability) to 40 (severe disability), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Time frame: Baseline, Week 48
Change From Baseline in UWDRS Part III Total Score at Week 48
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items \[disability\], items 2 to 11 \[10 items in total\]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 \[23 items in total\]). The UWDRS Part I and III was assessed by a neurologist who was blinded to the treatment randomization. The UWDRS Part III total score was calculated as the sum of Question 12 to Question 34. The UWDRS Part III total score ranges from 0 (normal) to 175 (severe disease), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
Time frame: Baseline, Week 48
Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
UWDRS Part III Functional Subscale consists of speech, handwriting, arising from chair, and gait from UWDRS Part III. The standardized score of the first 3 items ranges from 0 (normal) to 10 (worst), and standardized transformed score of gait ranges from 0 (normal) to 10 (worst). The average of these scores was used to create the Part III Functional Subscale with a range of 0 (normal) - 10 (worst) with higher scores indicating more functional disability.
Time frame: Baseline, Week 48
Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48
UWDRS Part III individual items speech, handwriting, arising from chair, and gait are reported here. For speech (Question 12), original score ranges from 0 (normal) to 4 (unintelligible). For handwriting (Question 20), original score ranges from 0 (normal) to 4 (cannot hold a pen). For arising from chair (Question 27), original score ranges from 0 (normal) to 4 (unable to arise without help). For gait (Question 29), the original score (range: 0 \[normal\] to 10 \[severe condition\]) was calculated by summing subscores (0 \[normal\] to 4 \[severe\]) of Part A (Right and Left Leg dystonia), B (Ataxia), and C (Parkinsonism).
Time frame: Baseline, Week 48
Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time frame: Week 48
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at time of rating as: 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.
Time frame: Baseline, Week 48
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
The MELD score uses the participant's values for bilirubin, creatinine, and the international normalized ratio (INR). The initial MELD score (MELD\[i\]) is calculated according to the following formula: MELD(i) = 3.78\*ln\[serum bilirubin (mg/dL)\] + 11.2\*ln\[INR\] + 9.57\*ln\[serum creatinine (mg/dL)\] + 6.43. Creatinine, bilirubin, and INR values less than 1.0 are set to 1.0 and creatinine values greater than 4.0 are set to 4.0 when calculating MELD(i). Additionally, creatinine, bilirubin, and INR are rounded to the 10th decimal place prior to performing the calculation. The initial MELD score is then rounded to the nearest integer. The MELD score ranges from 6 (least sick) - 40 (most sick), with higher values indicating more advanced disease.
Time frame: Baseline, Week 48
Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48
cNCC = Plasma Total Copper (Cu) \[micrograms (µg)/L\]-(3.15\*ceruloplasmin \[milligrams (mg)/L\])/63.5 \[µg/µmol\] For ALXN1840-treated participants, cNCC in plasma corrected for amount of Cu bound to ALXN1840 tripartite complex (TPC) cNCCcorrected = (√cNCC- 0.993)2√Mo, (Mo= molybdenum). In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration \<lower limit of quantification (LLOQ), cNCC was considered missing (LLOQ = 20 nanograms \[ng\]/mL); - Serum ceruloplasmin concentration values \<LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values \<LLOQ are set to 0 (LLOQ = 1 ng/L); - If cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo \> √cNCC.
Time frame: Baseline, Week 48
Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
cNCC \[µmol/L\] = Plasma Total Cu \[µg/L\]-(3.15\*ceruloplasmin \[mg/L\])/63.5 \[µg/µmol\] For ALXN1840-treated participants, cNCC in plasma was corrected for amount of Cu bound to the ALXN1840 TPC using square root-based cNCC correction method: cNCCcorrected = (√cNCC- 0.993)2√Mo, where Mo = molybdenum. In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration values \<LLOQ, cNCC was considered missing (LLOQ = 20 ng/mL); - Serum ceruloplasmin concentration values \<LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values \<LLOQ are set to 0 (LLOQ = 1 ng/L); - In cases where cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo \> √cNCC.
Time frame: Baseline, Week 48
cNCC/cNCCcorrected Responder at Week 48
cNCC/cNCCcorrected responder was defined as participants who achieved or maintained normalized cNCC/cNCCcorrected concentration (0.8-2.3 μmol) within (at or before) 48 weeks or reached a reduction of at least 25% in cNCC/cNCCcorrected within 48 weeks. Thus, a participant was considered a cNCC/cNCCcorrected responder if they met at least 1 of the following criteria: - Achieved normalized cNCC/cNCCcorrected concentration for 2 consecutive measurements within 48 weeks, for participants who had elevated cNCC concentrations at baseline; - Maintained normalized cNCC/cNCCcorrected concentration within 48 weeks, for participants who had normal cNCC concentrations at baseline; - Reached a reduction of at least 25% in cNCC/cNCCcorrected for 2 consecutive measurements within 48 weeks.
Time frame: Week 48
The study consisted of 2 periods: Primary Evaluation Period (PEP) and Open-label Extension (OLE) Period. Participants who completed the 48-week PEP were offered the opportunity to continue treatment in an up to 60-month Extension. A total of 214 participants were randomized; 207 participants were treated in the PEP.
| Milestone | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 |
|---|---|---|---|---|---|---|
| Started | 105 | 56 | 37 | 16 | 0 | 0 |
| Received at least 1 dose of study drug | 104 | 56 | 33 | 14 | 0 | 0 |
| Completed pep, enter extension | 89 | 49 | 28 | 12 | 0 | 0 |
| Completed pep, not into extension | 4 | 3 | 1 | 1 | 0 | 0 |
| Completed | 93 | 52 | 29 | 13 | 0 | 0 |
| Not completed | 12 | 4 | 8 | 3 | 0 | 0 |
| Withdrew: Withdrawal by subject | 4 | 2 | 2 | 1 | 0 | 0 |
| Withdrew: Adverse event | 4 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Death | 1 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol deviation | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Randomized but not treated | 1 | 0 | 4 | 2 | 0 | 0 |
| Milestone | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 |
|---|---|---|---|---|---|---|
| Started | 89 | 49 | 28 | 12 | 8 | 11 |
| Completed | 0 | 0 | 0 | 0 | 0 | 1 |
| Not completed | 89 | 49 | 28 | 12 | 8 | 10 |
| Withdrew: Withdrawal by subject | 6 | 7 | 2 | 1 | 0 | 2 |
| Withdrew: Adverse event | 6 | 3 | 1 | 1 | 0 | 0 |
| Withdrew: Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol deviation | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 66 | 32 | 21 | 10 | 7 | 8 |
| Withdrew: Other than specified | 5 | 5 | 3 | 0 | 1 | 0 |
| Withdrew: Physician decision | 2 | 1 | 1 | 0 | 0 | 0 |
dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).
| micromoles (µmol)*hours (hr)/liter (L) | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W) | 2.50 ± 0.150 | 0.87 ± 0.204 | 4.76 ± 0.319 | 0.96 ± 0.487 |
An AE was any untoward medical occurrence in a participant administered the study drug and which did not necessarily have a causal relationship with this treatment. TEAEs were defined as those AEs with onset after the first dose of randomized treatment or existing events that worsened in severity after the first dose of randomized treatment. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Participants | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 89 | 41 | 30 | 12 |
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items \[disability\], items 2 to 11 \[10 items in total\]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 \[23 items in total\]). The UWDRS Part II total score was calculated as the sum of Question 2 to Question 11 (each question has range 0 \[none\] to 4 \[severe\]). The UWDRS Part II total score ranges from 0 (no disability) to 40 (severe disability), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48 | -0.7 ± 2.75 | 0.0 ± 2.31 | -0.5 ± 3.23 | -1.8 ± 4.63 |
The UWDRS comprises 3 parts: UWDRS Part I (level of consciousness, item 1), UWDRS Part II (a patient-reported review of daily activity items \[disability\], items 2 to 11 \[10 items in total\]), and UWDRS Part III (a detailed neurological examination, items 12 to 34 \[23 items in total\]). The UWDRS Part I and III was assessed by a neurologist who was blinded to the treatment randomization. The UWDRS Part III total score was calculated as the sum of Question 12 to Question 34. The UWDRS Part III total score ranges from 0 (normal) to 175 (severe disease), with lower score indicating improvement in condition and a better outcome. Change from baseline was calculated as: postbaseline assessment value - baseline assessment value when both values were not missing.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Change From Baseline in UWDRS Part III Total Score at Week 48 | -2.24 ± 7.458 | -1.59 ± 6.188 | -2.06 ± 9.843 | 1.55 ± 5.889 |
UWDRS Part III Functional Subscale consists of speech, handwriting, arising from chair, and gait from UWDRS Part III. The standardized score of the first 3 items ranges from 0 (normal) to 10 (worst), and standardized transformed score of gait ranges from 0 (normal) to 10 (worst). The average of these scores was used to create the Part III Functional Subscale with a range of 0 (normal) - 10 (worst) with higher scores indicating more functional disability.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48 | -0.165 ± 0.7620 | -0.102 ± 0.5467 | -0.090 ± 0.8464 | 0.227 ± 0.4214 |
UWDRS Part III individual items speech, handwriting, arising from chair, and gait are reported here. For speech (Question 12), original score ranges from 0 (normal) to 4 (unintelligible). For handwriting (Question 20), original score ranges from 0 (normal) to 4 (cannot hold a pen). For arising from chair (Question 27), original score ranges from 0 (normal) to 4 (unable to arise without help). For gait (Question 29), the original score (range: 0 \[normal\] to 10 \[severe condition\]) was calculated by summing subscores (0 \[normal\] to 4 \[severe\]) of Part A (Right and Left Leg dystonia), B (Ataxia), and C (Parkinsonism).
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Speech | -0.1 ± 0.50 | 0.0 ± 0.35 | -0.1 ± 0.52 | 0.1 ± 0.54 |
| Handwriting | -0.2 ± 0.63 | -0.1 ± 0.48 | 0.1 ± 0.60 | 0.2 ± 0.40 |
| Arising from a chair | 0.0 ± 0.45 | -0.1 ± 0.56 | 0.0 ± 0.27 | 0.0 ± 0.00 |
| Gait | -0.03 ± 1.317 | 0.00 ± 1.141 | -0.18 ± 0.945 | 0.23 ± 0.754 |
The CGI-I is a 7-point scale where the clinician assessed how much participant's illness improved or worsened relative to a Baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48 | 3.4 ± 0.89 | 3.8 ± 0.80 | 3.1 ± 1.06 | 3.2 ± 1.34 |
The CGI-S is a 7-point scale where the investigator rated severity of participant's illness at the time of assessment, relative to the investigator's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of illness at time of rating as: 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.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48 | -0.4 ± 0.79 | -0.1 ± 0.73 | -0.6 ± 1.11 | -0.5 ± 1.21 |
The MELD score uses the participant's values for bilirubin, creatinine, and the international normalized ratio (INR). The initial MELD score (MELD\[i\]) is calculated according to the following formula: MELD(i) = 3.78\*ln\[serum bilirubin (mg/dL)\] + 11.2\*ln\[INR\] + 9.57\*ln\[serum creatinine (mg/dL)\] + 6.43. Creatinine, bilirubin, and INR values less than 1.0 are set to 1.0 and creatinine values greater than 4.0 are set to 4.0 when calculating MELD(i). Additionally, creatinine, bilirubin, and INR are rounded to the 10th decimal place prior to performing the calculation. The initial MELD score is then rounded to the nearest integer. The MELD score ranges from 6 (least sick) - 40 (most sick), with higher values indicating more advanced disease.
| units on a scale | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48 | -0.1 ± 1.85 | 0.1 ± 1.32 | -0.7 ± 1.61 | 0.2 ± 1.25 |
cNCC = Plasma Total Copper (Cu) \[micrograms (µg)/L\]-(3.15\*ceruloplasmin \[milligrams (mg)/L\])/63.5 \[µg/µmol\] For ALXN1840-treated participants, cNCC in plasma corrected for amount of Cu bound to ALXN1840 tripartite complex (TPC) cNCCcorrected = (√cNCC- 0.993)2√Mo, (Mo= molybdenum). In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration \<lower limit of quantification (LLOQ), cNCC was considered missing (LLOQ = 20 nanograms \[ng\]/mL); - Serum ceruloplasmin concentration values \<LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values \<LLOQ are set to 0 (LLOQ = 1 ng/L); - If cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo \> √cNCC.
| µmol/L | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48 | -0.72 ± 1.107 | 0.64 ± 2.769 | -1.95 ± 1.536 | -1.51 ± 2.361 |
cNCC \[µmol/L\] = Plasma Total Cu \[µg/L\]-(3.15\*ceruloplasmin \[mg/L\])/63.5 \[µg/µmol\] For ALXN1840-treated participants, cNCC in plasma was corrected for amount of Cu bound to the ALXN1840 TPC using square root-based cNCC correction method: cNCCcorrected = (√cNCC- 0.993)2√Mo, where Mo = molybdenum. In calculation of cNCC and cNCCcorrected following rules apply: - For plasma total Cu concentration values \<LLOQ, cNCC was considered missing (LLOQ = 20 ng/mL); - Serum ceruloplasmin concentration values \<LLOQ are set to 0 (LLOQ = 22.5 mg/L); - Plasma total Mo concentration values \<LLOQ are set to 0 (LLOQ = 1 ng/L); - In cases where cNCC calculation produces a negative result, cNCC was considered missing and cNCCcorrected was not derived; - cNCCcorrected was set to 0 when 0.993√Mo \> √cNCC.
| percent change | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48 | -7.7 ± 263.20 | 104.6 ± 292.11 | -64.0 ± 42.88 | -44.3 ± 68.82 |
cNCC/cNCCcorrected responder was defined as participants who achieved or maintained normalized cNCC/cNCCcorrected concentration (0.8-2.3 μmol) within (at or before) 48 weeks or reached a reduction of at least 25% in cNCC/cNCCcorrected within 48 weeks. Thus, a participant was considered a cNCC/cNCCcorrected responder if they met at least 1 of the following criteria: - Achieved normalized cNCC/cNCCcorrected concentration for 2 consecutive measurements within 48 weeks, for participants who had elevated cNCC concentrations at baseline; - Maintained normalized cNCC/cNCCcorrected concentration within 48 weeks, for participants who had normal cNCC concentrations at baseline; - Reached a reduction of at least 25% in cNCC/cNCCcorrected for 2 consecutive measurements within 48 weeks.
| Participants | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy |
|---|---|---|---|---|
| cNCC/cNCCcorrected Responder at Week 48 | 101 | 39 | 33 | 13 |
Collected over For PEP participants: From Primary Evaluation Period Baseline up to Primary Evaluation Period Week 48/Early Termination; For OLE and WTX101-201 participants: From Extension Period Week 1 up to Extension Period Week 268/Early Termination. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PEP Cohort 1: ALXN1840 | 1/104 (1%) | 14/104 (13.5%) | 46/104 (44.2%) |
| PEP Cohort 1: SoC Therapy | 0/56 (0%) | 6/56 (10.7%) | 18/56 (32.1%) |
| PEP Cohort 2: ALXN1840 | 1/33 (3%) | 4/33 (12.1%) | 16/33 (48.5%) |
| PEP Cohort 2: SoC Therapy | 0/14 (0%) | 0/14 (0%) | 7/14 (50%) |
| OLE Cohort 1: ALXN1840 | 1/89 (1.1%) | 20/89 (22.5%) | 45/89 (50.6%) |
| OLE Cohort 1: SoC Therapy | 0/49 (0%) | 10/49 (20.4%) | 32/49 (65.3%) |
| OLE Cohort 2: ALXN1840 | 0/28 (0%) | 6/28 (21.4%) | 10/28 (35.7%) |
| OLE Cohort 2: SoC Therapy | 0/12 (0%) | 3/12 (25%) | 4/12 (33.3%) |
| Cohort 1: WTX101-201- ALXN1840 | 0/8 (0%) | 2/8 (25%) | 6/8 (75%) |
| Cohort 2: WTX101-201- ALXN1840 | 0/11 (0%) | 3/11 (27.3%) | 7/11 (63.6%) |
| Event | PEP Cohort 1: ALXN1840 | PEP Cohort 1: SoC Therapy | PEP Cohort 2: ALXN1840 | PEP Cohort 2: SoC Therapy | OLE Cohort 1: ALXN1840 | OLE Cohort 1: SoC Therapy | OLE Cohort 2: ALXN1840 | OLE Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 |
|---|---|---|---|---|---|---|---|---|---|---|
| Coronary artery occlusionCardiac disorders | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 1/8 | 0/11 |
| MalnutritionMetabolism and nutrition disorders | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 1/8 | 0/11 |
| Microcytic anaemiaBlood and lymphatic system disorders | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 1/11 |
| COVID-19 pneumoniaInfections and infestations | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 1/11 |
| Anal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 1/11 |
| SciaticaNervous system disorders | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 1/11 |
| Umbilical herniaGastrointestinal disorders | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 1/12 | 0/8 | 0/11 |
| Burns second degreeInjury, poisoning and procedural complications | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 1/12 | 0/8 | 0/11 |
| Procedural painInjury, poisoning and procedural complications | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 1/12 | 0/8 | 0/11 |
| Sports injuryInjury, poisoning and procedural complications | 0/104 | 0/56 | 0/33 | 0/14 | 0/89 | 0/49 | 0/28 | 1/12 | 0/8 | 0/11 |
| Event | PEP Cohort 1: ALXN1840 | PEP Cohort 1: SoC Therapy | PEP Cohort 2: ALXN1840 | PEP Cohort 2: SoC Therapy | OLE Cohort 1: ALXN1840 | OLE Cohort 1: SoC Therapy | OLE Cohort 2: ALXN1840 | OLE Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 |
|---|---|---|---|---|---|---|---|---|---|---|
| COVID-19Infections and infestations | 0/104 | 0/56 | 0/33 | 0/14 | 22/89 | 12/49 | 6/28 | 4/12 | 2/8 | 7/11 |
| Alanine aminotransferase increasedInvestigations | 19/104 | 1/56 | 1/33 | 1/14 | 8/89 | 13/49 | 2/28 | 1/12 | 1/8 | 1/11 |
| NasopharyngitisInfections and infestations | 11/104 | 10/56 | 4/33 | 2/14 | 9/89 | 6/49 | 2/28 | 3/12 | 0/8 | 0/11 |
| HeadacheNervous system disorders | 7/104 | 3/56 | 4/33 | 3/14 | 8/89 | 6/49 | 0/28 | 1/12 | 1/8 | 1/11 |
| NauseaGastrointestinal disorders | 6/104 | 1/56 | 2/33 | 2/14 | 6/89 | 3/49 | 1/28 | 1/12 | 1/8 | 0/11 |
| Urinary tract infectionInfections and infestations | 0/104 | 0/56 | 0/33 | 0/14 | 5/89 | 5/49 | 0/28 | 0/12 | 1/8 | 0/11 |
| FatigueGeneral disorders | 9/104 | 2/56 | 4/33 | 1/14 | 4/89 | 6/49 | 1/28 | 0/12 | 0/8 | 1/11 |
| TremorNervous system disorders | 6/104 | 1/56 | 4/33 | 1/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 0/11 |
| Upper respiratory tract infectionInfections and infestations | 8/104 | 3/56 | 1/33 | 0/14 | 0/89 | 0/49 | 0/28 | 0/12 | 0/8 | 0/11 |
The Full Analysis Set included all randomized participants who received at least 1 dose of randomized treatment. The Extension Analysis Set included all participants who entered the Extension Period and received at least 1 dose of ALXN1840 in the Extension Period. This included the participants who rolled over from Study WTX101-201.
| Age, Customized(Participants) | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 | Total |
|---|---|---|---|---|---|---|---|
| ≥12 years - <18 years | 10 | 4 | 2 | 2 | 0 | 0 | 18 |
| ≥18 years - <65 years | 92 | 50 | 31 | 12 | 7 | 11 | 203 |
| ≥65 years | 2 | 2 | 0 | 0 | 1 | 0 | 5 |
| Sex: Female, Male(Participants) | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 | Total |
|---|---|---|---|---|---|---|---|
| Female | 46 | 30 | 9 | 3 | 3 | 7 | 98 |
| Male | 58 | 26 | 24 | 11 | 5 | 4 | 128 |
| Race/Ethnicity, Customized(Participants) | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 | Total |
|---|---|---|---|---|---|---|---|
| Race — Asian | 19 | 13 | 5 | 0 | 1 | 1 | 39 |
| Race — Black or African American | 1 | 2 | 0 | 0 | 0 | 0 | 3 |
| Race — White | 80 | 41 | 27 | 12 | 7 | 9 | 176 |
| Race — Other | 3 | 0 | 0 | 2 | 0 | 0 | 5 |
| Race — Unknown | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Race — Not Reported | 1 | 0 | 0 | 0 | 0 | 1 | 2 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: ALXN1840 | Cohort 1: SoC Therapy | Cohort 2: ALXN1840 | Cohort 2: SoC Therapy | Cohort 1: WTX101-201- ALXN1840 | Cohort 2: WTX101-201- ALXN1840 | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 0 | 2 | 1 | 0 | 7 |
| Not Hispanic or Latino | 101 | 54 | 32 | 11 | 7 | 11 | 216 |
| Unknown or Not Reported | 1 | 0 | 1 | 1 | 0 | 0 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting information: Study protocol, Statistical analysis plan
Time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Ran from Feb 2018 to primary completion in Jun 2023, 64 months.
Results were first posted in Oct 2023, 3 months after primary completion. A results delay was requested in Jan 2022.
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Studies of the drug tested here: Tetrathiomolybdate
Hepatolenticular Degeneration →
Alexion Pharmaceuticals, Inc. →