Trial Outcomes & Findings for Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients (NCT NCT02273596)
NCT ID: NCT02273596
Last Updated: 2021-09-29
Results Overview
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole \[μmol\]l/liter \[L\]\]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.
COMPLETED
PHASE2
29 participants
Week 24
2021-09-29
Participant Flow
Participants meeting all inclusion and no exclusion criteria were enrolled into the study and studied as outpatients. Participants enrolled as pre-treated with other de-coppering agents were required to undergo a 48-hour washout from their previous Wilson Disease (WD) treatment just prior to initiation of study treatment. Participants who completed the 24-week treatment period and had favorable safety profiles and WD control were offered the opportunity to participate in the Extension Period.
Participant milestones
| Measure |
ALXN1840
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligrams (mg) per day. Dose increases or dose reductions were dependent on the individual non-ceruloplasmin-bound copper (NCC) concentrations adjusted for molybdenum (Mo) plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range.
|
|---|---|
|
24-Week Treatment Period
STARTED
|
29
|
|
24-Week Treatment Period
Received at Least 1 Dose of Study Drug
|
28
|
|
24-Week Treatment Period
COMPLETED
|
22
|
|
24-Week Treatment Period
NOT COMPLETED
|
7
|
|
Extension Period
STARTED
|
22
|
|
Extension Period
Received at Least 1 Dose of Study Drug
|
22
|
|
Extension Period
COMPLETED
|
0
|
|
Extension Period
NOT COMPLETED
|
22
|
Reasons for withdrawal
| Measure |
ALXN1840
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligrams (mg) per day. Dose increases or dose reductions were dependent on the individual non-ceruloplasmin-bound copper (NCC) concentrations adjusted for molybdenum (Mo) plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range.
|
|---|---|
|
24-Week Treatment Period
Adverse Event
|
3
|
|
24-Week Treatment Period
Withdrawal by Participant Prior to First Dose
|
1
|
|
24-Week Treatment Period
Participant was unable to Come
|
1
|
|
24-Week Treatment Period
Physician Decision
|
1
|
|
24-Week Treatment Period
Protocol Deviation
|
1
|
|
Extension Period
Continued into Study WTX101-301 extension (NCT03403205).
|
19
|
|
Extension Period
Participant Withdrew for Personal Reasons
|
1
|
|
Extension Period
Lost to Follow-up
|
1
|
|
Extension Period
Protocol Deviation
|
1
|
Baseline Characteristics
Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients
Baseline characteristics by cohort
| Measure |
ALXN1840
n=28 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
34.1 years
STANDARD_DEVIATION 11.86 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: Participants who were enrolled and received at least 1 dose of study drug.
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole \[μmol\]l/liter \[L\]\]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.
Outcome measures
| Measure |
ALXN1840
n=28 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Percentage Of Participants With Normalized Concentrations Of NCC
|
85.7 percentage of participants
Interval 70.8 to 97.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The change from Baseline in NCC adjusted for Mo plasma concentration over 24 weeks were analyzed and descriptive statistics are reported. Change from Baseline = (Week 24 NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% confidence intervals (CIs) were calculated using a restricted maximum likelihood (REML)-based mixed model for repeated measures (MMRM) with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Outcome measures
| Measure |
ALXN1840
n=21 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24
|
-2.56 μmol/L
Interval -3.13 to -1.98
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to last assessment (up to Week 176)Population: This analysis was only performed on the subset of participants with elevated Baseline NCC who reached the event of normalization of NCC corrected concentrations.
For time to normalization of NCC adjusted for Mo plasma concentration, a Kaplan-Meier approach was used where participants not normalized were censored at the latest observed time point. To achieve a normalized NCC concentration, participants must have demonstrated 2 consecutive measures within the normal range (0.8 to 2.3 μmol/L). Analyses includes all data up to the last assessment in the extension period for participants who reached the event of normalization of NCC corrected concentrations. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Outcome measures
| Measure |
ALXN1840
n=16 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC
|
147.5 days
Interval 37.0 to 211.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. Change from Baseline in the UWDRS I for consciousness is presented. * UWDRS I: range 0 to 3, maximum score of 3 * UWDRS I was assessed by a Neurologist * Change from Baseline was calculated as: Week 24 score - Baseline score. A decrease in score from Baseline is indicative of both an improvement in condition and a better outcome.
Outcome measures
| Measure |
ALXN1840
n=22 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24
|
0.0 score on a scale
Standard Deviation 0.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The UWDRS is a clinical rating scale designed to evaluate the neurological manifestations of WD. UWDRS comprises 3 parts: UWDRS I (consciousness), UWDRS II (disability), and UWDRS III (neurological status). Change from Baseline in the UWDRS II, III, and total score are presented. * UWDRS I: range 0 to 3, maximum score of 3 * UWDRS II: range 0 to 40, maximum score of 40 * UWDRS III: range 0 to 175, maximum score of 175 * UWDRS total score: sum of the UWDRS I, II, and III: range 0 to 218, maximum score of 218 * UWDRS I and III were assessed by a neurologist, while UWDRS II was reported by the participant or caregiver. * Change from Baseline was calculated as: Week 24 score - Baseline score. Least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. A decrease in score from Baseline is indicative of an improvement in condition and a better outcome.
Outcome measures
| Measure |
ALXN1840
n=22 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
UWDRS Part II
|
-2.5 score on a scale
Interval -4.6 to -0.4
|
—
|
—
|
—
|
|
Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
UWDRS Part III
|
-5.75 score on a scale
Interval -10.74 to -0.77
|
—
|
—
|
—
|
|
Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24
Total Score
|
-8.23 score on a scale
Interval -15.42 to -1.04
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The M.I.N.I. is a short structured diagnostic interview for the Diagnostic and Statistical Manual of Mental Disorders IV and the 10th revision of the International Statistical Classification of Diseases and Related Health Problems. It was used to "track" the severity of symptoms by using a combination of questions in 16 Psychiatric Status dimensions that are summarized using a single standardized score for each dimension, ranging from 0 (interpreted as "did not occur at all") to 4 (interpreted as "occurred extremely often"). The standardized score is an average of these responses. Change from Baseline = Week 24 standardized score - Baseline standardized score. Least square means and 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction. Decrease from Baseline (a lower score) is indicative of a decrease in symptoms and a better outcome.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Major Depressive Episode Standardized
|
-0.39 score on a scale
Interval -0.62 to -0.16
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Suicidality Tracking Scale Standardized
|
-0.07 score on a scale
Interval -0.09 to -0.04
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Manic/Hypomanic Episode Standardized
|
-0.09 score on a scale
Interval -0.23 to 0.05
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Panic Disorder Standardized
|
-0.28 score on a scale
Interval -0.35 to -0.21
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Agoraphobia Standardized
|
-0.58 score on a scale
Interval -0.7 to -0.46
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Social Anxiety Disorder Standardized
|
-0.35 score on a scale
Interval -0.52 to -0.18
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Obsessive Compulsive Disorder Standardized
|
-0.04 score on a scale
Interval -0.14 to 0.05
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Post Traumatic Stress Disorder Standardized
|
-0.24 score on a scale
Interval -0.35 to -0.13
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Alcohol Use Disorder Standardized
|
0.00 score on a scale
Interval -0.03 to 0.03
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Substance Use Disorder Standardized
|
-0.02 score on a scale
Interval -0.1 to 0.05
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Psychotic Disorders Standardized
|
0.00 score on a scale
Interval -0.06 to 0.07
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Anorexia Nervosa Standardized
|
0.04 score on a scale
Interval -0.07 to 0.15
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Bulimia Nervosa Standardized
|
0.0 score on a scale
Interval -0.12 to 0.13
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Binge Eating Disorder Standardized
|
0.04 score on a scale
Interval -0.06 to 0.14
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Generalized Anxiety Disorder Standardized
|
-0.37 score on a scale
Interval -0.59 to -0.16
|
—
|
—
|
—
|
|
Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24
Antisocial Personality Disorder Standardized
|
-0.06 score on a scale
Interval -0.12 to 0.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
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. Change from Baseline = Week 24 score - Baseline score. An increase in CGI-I score indicates improvement.
Outcome measures
| Measure |
ALXN1840
n=22 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Clinical Global Impression-Improvement Scale (CGI-I) At Week 24
|
-0.8 score on a scale
Interval -1.4 to -0.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
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. Change from Baseline = Week 24 score - Baseline score. Decrease in CGI-S score and increase indicates improvement.
Outcome measures
| Measure |
ALXN1840
n=8 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) At Week 24
|
-0.9 score on a scale
Interval -1.7 to 0.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The EQ-5D VAS records the participant's self-rated health as indicated on a scale from 0 to 100 with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine, with higher scores for a higher quality of life. Change from Baseline = Week 24 score - Baseline score. An increase in score indicates improvement. The least-square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The European Quality Of Life 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) At Week 24
|
11.3 score on a scale
Interval 5.1 to 17.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The EQ-5D-5L Descriptive System provides a simple descriptive profile and a single index value for health status (United Kingdom \[UK\] Health Index Score). The EQ-5D-5L consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each of which can have 1 of 5 responses that represent 5 levels of severity (no problems, slight problems, moderate problems, severe problems, extreme problems). The participant was asked to indicate his/her health state for each of the 5 dimensions. The 5-item index score was transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from Baseline = Week 24 index score - Baseline index score. An increase in score indicates improvement. The least square means and their 95% CIs were calculated using a REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The EQ-5D Descriptive System UK Health Index Scores At Week 24
|
0.0439 EQ-5D-5L index score
Interval -0.0341 to 0.1219
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The MMAS-8 is a scale used to evaluate adherence to medication. The MMAS-8 consists of 8 questions with a sum score ranging between 0 and 8 points, with 8 being the maximum adherence to medication. Mean adherence to medication is presented.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
QoL/PRO Assessed By The 8-Item Medication Adherence Scale (MMAS-8) At Week 24
|
7.59 score on a scale
Interval 7.29 to 7.88
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The TSQM-9 was used to assess the overall level of satisfaction or dissatisfaction with medication participants were taking. This composite scale is comprised of 2 items on the TSQM-9 survey: How satisfied are you that good things about this medication outweigh the bad things? Taking all things into account, how satisfied or dissatisfied are you with this medication? The TSQM-9 domain scores (effectiveness score, convenience score, global satisfaction score) range from 0 to 100 with higher scores representing greater satisfaction for the domain.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
Effectiveness
|
69.81 score on a scale
Interval 58.9 to 80.72
|
—
|
—
|
—
|
|
QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
Convenience
|
83.57 score on a scale
Interval 77.62 to 89.53
|
—
|
—
|
—
|
|
QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24
Global Satisfaction
|
75.47 score on a scale
Interval 62.77 to 88.16
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 ALT level - Baseline ALT level.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Hepatic Laboratory Measure Alanine Aminotransferase (ALT) At Week 24
|
-2.0 U/L
Standard Deviation 23.71
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 AST level - Baseline AST level.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Hepatic Laboratory Measure Aspartate Aminotransferase (AST) At Week 24
|
-10.3 U/L
Standard Deviation 28.18
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 INR - Baseline INR.
Outcome measures
| Measure |
ALXN1840
n=22 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Hepatic Laboratory Measure International Normalized Ratio (INR) At Week 24
|
-0.05 ratio
Standard Deviation 0.148
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 bilirubin level - Baseline bilirubin level.
Outcome measures
| Measure |
ALXN1840
n=23 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Hepatic Laboratory Measure Bilirubin At Week 24
|
-0.7 μmol/L
Standard Deviation 4.30
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 Exchangeable Cu level - Baseline Exchangeable Cu level.
Outcome measures
| Measure |
ALXN1840
n=22 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In Exchangeable Cu At Week 24
|
-25.1 ng/mL
Standard Deviation 56.64
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Due to low chromatographic resolution of data, quantitative analysis for speciation profiling, as had been planned in the protocol, was not feasible.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
Assessed by laboratory measurements. Change from Baseline = Week 24 (24-hour) urinary Mo or Cu level - Baseline 24-hour urinary Mo or Cu level.
Outcome measures
| Measure |
ALXN1840
n=20 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24
Mo
|
1561.1 μg/day
Interval 1093.8 to 2028.4
|
—
|
—
|
—
|
|
Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24
Cu
|
-28.1 μg/day
Interval -107.1 to 51.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had any Baseline and post-Baseline measurable concentration data reported.
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
Outcome measures
| Measure |
ALXN1840
n=1 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
n=4 Participants
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
n=16 Participants
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
n=6 Participants
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
Week 24
|
5668.7 h*ng/mL
Standard Deviation NA
Not available due to small sample size
|
4593.6 h*ng/mL
Standard Deviation 1260.0
|
7884.3 h*ng/mL
Standard Deviation 3157.2
|
8890.2 h*ng/mL
Standard Deviation 5801.6
|
|
Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
Day 1
|
—
|
2872.6 h*ng/mL
Standard Deviation 943.4
|
4796.7 h*ng/mL
Standard Deviation 3464.8
|
3138.7 h*ng/mL
Standard Deviation 3090.3
|
|
Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo
Week 12
|
—
|
7873.6 h*ng/mL
Standard Deviation 3361.1
|
8836.9 h*ng/mL
Standard Deviation 2675.9
|
11342.5 h*ng/mL
Standard Deviation 4706.7
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24Population: Participants who were enrolled and received at least 1 dose of study drug and had any Baseline and post-Baseline measurable concentration data reported.
PK blood sampling occurred on Day 1, Week 12, and Week 24 at the following serial PK sampling time-points: 0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose.
Outcome measures
| Measure |
ALXN1840
n=1 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
n=6 Participants
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
n=19 Participants
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
n=7 Participants
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
PK: Maximum Concentration (Cmax) Of Plasma Total Mo
Day 1
|
—
|
202.7 ng/mL
Standard Deviation 114.5
|
304.8 ng/mL
Standard Deviation 202.9
|
167.6 ng/mL
Standard Deviation 144.6
|
|
PK: Maximum Concentration (Cmax) Of Plasma Total Mo
Week 12
|
—
|
393.0 ng/mL
Standard Deviation 177.3
|
488.8 ng/mL
Standard Deviation 165.5
|
607.3 ng/mL
Standard Deviation 257.3
|
|
PK: Maximum Concentration (Cmax) Of Plasma Total Mo
Week 24
|
364.0 ng/mL
Standard Deviation NA
Not available due to small sample size
|
359.0 ng/mL
Standard Deviation 163.7
|
447.7 ng/mL
Standard Deviation 200.4
|
489.9 ng/mL
Standard Deviation 293.4
|
SECONDARY outcome
Timeframe: Up to last assessment (up to Week 176)Population: Participants who were enrolled and received at least 1 dose of study drug.
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8-2.3 μM) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of Cu bound to Cp from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period; up to Week 176.
Outcome measures
| Measure |
ALXN1840
n=28 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Extension Period: Percentage Of Participants With Normalized Concentrations Of NCC
|
92.9 percentage of participants
Interval 81.0 to 99.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, last assessment (up to Week 176)Population: Participants who were enrolled and received at least 1 dose of study drug and had analyzable data at the specified timepoint.
The change from Baseline in NCC adjusted for Mo plasma concentration over 176 weeks were analyzed. Last Assessment is a summary of the last available post-baseline result for each participant. Analyses includes all data up to the last assessment in the extension period, up to Week 176. Change from Baseline = (Last assessment \[up to Week 176\] NCC concentrations adjusted for Mo plasma concentration) - (Baseline NCC concentrations). Least square means and their 95% CIs were calculated using an REML-based MMRM with fixed effects for Baseline, cohort, visit, Baseline-by-visit, and cohort-by-visit interaction.
Outcome measures
| Measure |
ALXN1840
n=25 Participants
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
|
ALXN1840 15 mg Daily
ALXN1840 administered at 15 mg per day.
|
ALXN1840 30 mg Daily
ALXN1840 administered at 30 mg per day.
|
ALXN1840 60 mg Daily
ALXN1840 administered at 60 mg per day (or 30 mg twice daily).
|
|---|---|---|---|---|
|
Extension Period: Change From Baseline In NCC Levels Adjusted For Mo Plasma Concentration
|
-2.92 μmol/L
Interval -3.45 to -2.39
|
—
|
—
|
—
|
Adverse Events
ALXN1840
Serious adverse events
| Measure |
ALXN1840
n=28 participants at risk
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range.
|
|---|---|
|
Gastrointestinal disorders
Dysphagia
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
General disorders
Gait disturbance
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Alanine aminotransferase increased
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Hepatic enzyme increased
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Neurological decompensation
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Syncope
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Abnormal behaviour
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Adjustment disorder
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Affective disorder
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Mania
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Personality disorder
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Psychotic disorder
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Blood and lymphatic system disorders
Agranulocytosis
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Congenital, familial and genetic disorders
Hepato-lenticular degeneration
|
3.6%
1/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
Other adverse events
| Measure |
ALXN1840
n=28 participants at risk
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 mg per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Gastrointestinal disorders
Constipation
|
14.3%
4/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Gastrointestinal disorders
Nausea
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
General disorders
Fatigue
|
21.4%
6/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Infections and infestations
Urinary tract infection
|
28.6%
8/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Infections and infestations
Sinusitis
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Infections and infestations
Influenza
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Infections and infestations
Tonsillitis
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Injury, poisoning and procedural complications
Fall
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Alanine aminotransferase increased
|
35.7%
10/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Aspartate aminotransferase increased
|
32.1%
9/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Gamma-glutamyltransferase increased
|
28.6%
8/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Hepatic enzyme increased
|
21.4%
6/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Blood alkaline phosphatase increased
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Blood creatine phosphokinase increased
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Investigations
Liver function test increased
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
4/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Dupuytren's contracture
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Headache
|
21.4%
6/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Tremor
|
17.9%
5/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Dysgeusia
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Nervous system disorders
Paraesthesia
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Anxiety
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Depression
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Insomnia
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Sleep disorder
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Psychiatric disorders
Depressed mood
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.7%
3/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
4/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.1%
2/28 • Day 1 after dosing up to last assessment (up to Week 176), mean duration of treatment of 693.1 days
|
Additional Information
Alexion Pharmaceuticals Inc.
Alexion Pharmaceuticals Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place