Myasthenia Gravis, Myasthenia Gravis, Generalized, Myasthenia Gravis, Juvenile Form
Conditions
Keywords
Myasthenia Gravis, Myasthenia Gravis, Generalized
Brief summary
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of eculizumab in the treatment of pediatric refractory gMG based on change from Baseline in the Quantitative Myasthenia Gravis (QMG) score for disease severity.
Detailed description
The study will consist of an up to 4-week Screening Period, 26-week Primary Evaluation Treatment Period, an additional (up to) to 208-week Extension Period, and an 8-week Safety Follow-up Period.
Interventions
DRUGEculizumab
Eculizumab will be administered by IV infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Male or female pediatric participants 6 to \<18 years of age at time of assent/consent. * Vaccinated against Neisseria meningitidis. * Documented vaccination against Haemophilus influenzae and Streptococcus pneumoniae infections prior to dosing as per local and country specific immunization guidelines for the appropriate age group. * Diagnosis of MG confirmed by positive serologic test for anti-acetylcholine receptor antibodies at Screening, and 1 of the following: (a) history of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation; (b) history of positive anticholinesterase test (for example, edrophonium chloride or neostigmine test); or (c) participant demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors, as assessed by the Investigator. * Presence of refractory gMG, defined as participants with gMG who have 1 or more of the following: (a) failed treatment ≥1 year with at least 1 immunosuppressive therapies (IST), defined as follows: (1) persistent weakness with impairment of activities of daily living; (2) myasthenia gravis (MG) exacerbation and/or crisis while on treatment; or (3) intolerance to ISTs due to side effect or comorbid condition(s). (b) Require maintenance plasma exchange (PE) or intravenous immunoglobulin (IVIg) to control symptoms; and/or (c) in the opinion of the Investigator, MG poses a significant functional burden despite current MG treatment. * MGFA Clinical Classification of Class II to IV at Screening. * In patients aged 12 to 18 years, QMG total score ≥ 12 at Screening; in patients aged 6 to 11 years, no minimum QMG is required for inclusion; however, patients must have documented limb weakness in at least one limb. * All MG-specific treatment has been administered at a stable dosing regimen of adequate duration prior to Screening.
Exclusion criteria
* Parent or legal guardian is an Alexion employee. * Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening. * History of thymectomy within 12 months prior to Screening. * Are pregnant or lactating. * Any unresolved acute, or chronic, systemic bacterial or other infection, which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics. * Use of PE within 4 weeks prior to first dose. * Use of rituximab within 6 months prior to first dose. * Patients who are under 15 kg and are receiving maintenance IVIg. * Participation in another interventional treatment study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater. * Have previously received treatment with eculizumab or other complement inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment | Baseline, Week 26 | The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment | Week 26 | The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease. |
| Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment | Week 26 | The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease. |
| Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment | Week 26 | The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease. |
| Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment | Week 26 | The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease. |
| Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment | Baseline, Week 26 | The MGC is a validated assessment tool for measuring clinical status of participants with MG. The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross motor (2 items). The scales are weighted for clinical significance that incorporates patient-reported outcomes. The MGC total score ranges from 0 to 50, with lower scores indicating less functional impairment and higher scores indicating greater functional impairment. |
| Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Visual Analogue Scale (VAS) Score at Week 26 Regardless of Rescue Treatment | Baseline, Week 26 | The EQ-5D-Y is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each of which is completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participant \<12 years of age. Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme problems). The EQ visual analogue scale (VAS) records the participant's self-rated health on a vertical, 20-centimeter VAS where the endpoints are labelled 'Best imaginable health state, marked as 100' and 'Worst imaginable health state, marked as 0'. |
| Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment | Baseline, Week 26 | The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with myasthenia gravis (MG). The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease. |
| Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 | Week 26 | The MG clinical state (improved, unchanged, and worse) was assessed using the MGFAPIS. |
| Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use | Baseline up to Week 26 | Rescue therapy (for example, high dose corticosteroid, plasma exchange, or intravenous immunoglobulin) was to be allowed when a participant experienced clinical deterioration. Clinical deterioration was defined as follows: Participants who experienced an MG crisis, which was defined as weakness due to MG that was severe enough to necessitate intubation or to delay extubation following surgery; or, Significant symptomatic worsening that required rescue medication in the opinion of the Investigator; or, Participants for whom the Investigator believed that the participants' health was in jeopardy if rescue therapy was not given. |
| Pharmacokinetics (PK): Serum Concentration Of Eculizumab | 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26 | — |
| Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26 | — |
| PD: Percentage of Hemolysis (In Vitro Assay) | Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26 | — |
| Change From Baseline in the QMG Total Score at Week 52 Regardless of Rescue Treatment | Baseline, Week 52 | The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease. |
| Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment | Baseline, Week 26 | The Neuro-QoL Pediatric Fatigue questionnaire is a reliable and validated brief 11-item survey of fatigue, completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participants \<12 years of age. Each item was scored on a scale of 1 to 5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Total score is the sum of each item's score and it ranges from 11 to 55. Higher scores indicate greater fatigue and greater impact of MG on activities. |
Countries
Japan, United States
Participant flow
Recruitment details
The study included a Primary Evaluation Treatment Period of 26 weeks, an Extension Period of up to an additional 208 weeks, and a Follow-up Period of 8 weeks.
Pre-assignment details
All participants were offered participation in the Extension Period of the study.
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab Participants received eculizumab by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Period (Up to 208 Weeks) | Lost to Follow-up | 1 |
| Extension Period (Up to 208 Weeks) | Participant transferred to another study | 1 |
| Extension Period (Up to 208 Weeks) | Participant transitioned to Soliris | 1 |
| Extension Period (Up to 208 Weeks) | Participant transitioned to Ultomiris | 2 |
| Extension Period (Up to 208 Weeks) | Physician Decision | 1 |
| Extension Period (Up to 208 Weeks) | Withdrawal by Subject | 2 |
| Primary Evaluation Period (26 Weeks) | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Continuous | 14.8 years STANDARD_DEVIATION 1.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Quantitative Myasthenia Gravis (QMG) Total Score | 16.7 units on a scale STANDARD_DEVIATION 5.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 4 / 11 |
Outcome results
Primary
Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease.
Time frame: Baseline, Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment | -6.1 units on a scale | Standard Deviation 4.56 |
Comparison: The observed change in QMG was analyzed with baseline QMG score and visits as covariates.p-value: 0.000495% CI: [-8.4, -3.13]Repeated Measures Model
Secondary
Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Visual Analogue Scale (VAS) Score at Week 26 Regardless of Rescue Treatment
The EQ-5D-Y is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each of which is completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participant \<12 years of age. Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme problems). The EQ visual analogue scale (VAS) records the participant's self-rated health on a vertical, 20-centimeter VAS where the endpoints are labelled 'Best imaginable health state, marked as 100' and 'Worst imaginable health state, marked as 0'.
Time frame: Baseline, Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Visual Analogue Scale (VAS) Score at Week 26 Regardless of Rescue Treatment | 23.5 units on a scale | Standard Deviation 23.34 |
Secondary
Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with myasthenia gravis (MG). The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease.
Time frame: Baseline, Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment | -2.5 units on a scale | Standard Deviation 1.78 |
Secondary
Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment
The MGC is a validated assessment tool for measuring clinical status of participants with MG. The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross motor (2 items). The scales are weighted for clinical significance that incorporates patient-reported outcomes. The MGC total score ranges from 0 to 50, with lower scores indicating less functional impairment and higher scores indicating greater functional impairment.
Time frame: Baseline, Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment | -9.4 units on a scale | Standard Deviation 5.91 |
Secondary
Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment
The Neuro-QoL Pediatric Fatigue questionnaire is a reliable and validated brief 11-item survey of fatigue, completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participants \<12 years of age. Each item was scored on a scale of 1 to 5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Total score is the sum of each item's score and it ranges from 11 to 55. Higher scores indicate greater fatigue and greater impact of MG on activities.
Time frame: Baseline, Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment | -7.9 units on a scale | Standard Deviation 7.37 |
Secondary
Change From Baseline in the QMG Total Score at Week 52 Regardless of Rescue Treatment
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease.
Time frame: Baseline, Week 52
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Number Analyzed' and 'Overall Number of Participants Analyzed' signify those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eculizumab | Change From Baseline in the QMG Total Score at Week 52 Regardless of Rescue Treatment | -4.9 units on a scale | Standard Deviation 4.26 |
Comparison: The observed change in QMG was analyzed with baseline QMG score and visits as covariates.p-value: 0.003395% CI: [-6.93, -1.65]Repeated Measures Model
Secondary
Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26
The MG clinical state (improved, unchanged, and worse) was assessed using the MGFAPIS.
Time frame: Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Number Analyzed' and 'Overall Number of Participants Analyzed' signify those participants who were evaluable for this outcome measure.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eculizumab | Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 | Improved | 10 Participants |
| Eculizumab | Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 | Unchanged | 0 Participants |
| Eculizumab | Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 | Worse | 0 Participants |
Secondary
PD: Percentage of Hemolysis (In Vitro Assay)
Time frame: Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
Population: Pharmacodynamic Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab and who had PD data assessments during the study. Here, 'Number Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | PD: Percentage of Hemolysis (In Vitro Assay) | Baseline | 105.8 percentage of hemolysis | Standard Deviation 14.15 |
| Eculizumab | PD: Percentage of Hemolysis (In Vitro Assay) | Day 1, 24 hours postdose | 1.1 percentage of hemolysis | Standard Deviation 2.01 |
| Eculizumab | PD: Percentage of Hemolysis (In Vitro Assay) | Week 12, Predose | 1.8 percentage of hemolysis | Standard Deviation 4.67 |
| Eculizumab | PD: Percentage of Hemolysis (In Vitro Assay) | Week 12, 60 minutes postdose | 0.2 percentage of hemolysis | Standard Deviation 0.45 |
| Eculizumab | PD: Percentage of Hemolysis (In Vitro Assay) | Week 26, Predose | 0.5 percentage of hemolysis | Standard Deviation 1.29 |
Secondary
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease.
Time frame: Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eculizumab | Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment | 50.0 percentage of participants | 95% Confidence Interval 18.7 |
Secondary
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher scores indicating more severe disease.
Time frame: Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eculizumab | Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment | 50.0 percentage of participants | 95% Confidence Interval 18.7 |
Secondary
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease.
Time frame: Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eculizumab | Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment | 70.0 percentage of participants | 95% Confidence Interval 34.8 |
Secondary
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment
The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease.
Time frame: Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eculizumab | Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment | 70.0 percentage of participants | 95% Confidence Interval 34.8 |
Secondary
Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use
Rescue therapy (for example, high dose corticosteroid, plasma exchange, or intravenous immunoglobulin) was to be allowed when a participant experienced clinical deterioration. Clinical deterioration was defined as follows: Participants who experienced an MG crisis, which was defined as weakness due to MG that was severe enough to necessitate intubation or to delay extubation following surgery; or, Significant symptomatic worsening that required rescue medication in the opinion of the Investigator; or, Participants for whom the Investigator believed that the participants' health was in jeopardy if rescue therapy was not given.
Time frame: Baseline up to Week 26
Population: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab | Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use | Clinical Deterioration | 9.1 percentage of participants |
| Eculizumab | Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use | MG Crisis | 9.1 percentage of participants |
| Eculizumab | Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use | Requiring Rescue Therapy | 9.1 percentage of participants |
Secondary
Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations
Time frame: Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
Population: Pharmacodynamic Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab and who had PD data assessments during the study. Here, 'Number Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Baseline | 172.7 μg/mL | Standard Deviation 34.52 |
| Eculizumab | Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Day 1, 24 hours postdose | 0.0 μg/mL | Standard Deviation 0.01 |
| Eculizumab | Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Week 12, Predose | 0.0 μg/mL | Standard Deviation 0.01 |
| Eculizumab | Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Week 12, 60 minutes postdose | 0.0 μg/mL | Standard Deviation 0.01 |
| Eculizumab | Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations | Week 26, Predose | 0.0 μg/mL | Standard Deviation 0.02 |
Secondary
Pharmacokinetics (PK): Serum Concentration Of Eculizumab
Time frame: 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
Population: Pharmacokinetic Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab and who had PK data assessments during the study. Here, 'Number Analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Pharmacokinetics (PK): Serum Concentration Of Eculizumab | Day 1, 24 hours postdose | 359.6 micrograms (μg)/milliliter (mL) | Standard Deviation 105.18 |
| Eculizumab | Pharmacokinetics (PK): Serum Concentration Of Eculizumab | Week 12, Predose | 382.8 micrograms (μg)/milliliter (mL) | Standard Deviation 159.57 |
| Eculizumab | Pharmacokinetics (PK): Serum Concentration Of Eculizumab | Week 12, 60 minutes postdose | 910.5 micrograms (μg)/milliliter (mL) | Standard Deviation 277.29 |
| Eculizumab | Pharmacokinetics (PK): Serum Concentration Of Eculizumab | Week 26, Predose | 433.9 micrograms (μg)/milliliter (mL) | Standard Deviation 171.85 |