Generalized Myasthenia Gravis
Conditions
Brief summary
This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab compared with placebo in participants with generalized myasthenia gravis (gMG).
Interventions
DRUGSatralizumab
Satralizumab will be administered as a subcutaneous injection
OTHERPlacebo
Satralizumab placebo will be administered as a subcutaneous injection
Sponsors
Chugai Pharmaceutical
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * For adolescent patients: Informed Consent Form for study participation signed by the parents or a legal guardian, and patient assent obtained, as per local requirements * Ability to comply with the study protocol procedures * Confirmed diagnosis of gMG (anti-AChR, anti-MuSK or anti-LRP4 present at screening) * A total MG-ADL score of ≥ 5 points at screening with more than 50% of this score attributed to non-ocular items * MGFA severity Class II-IV * Ongoing gMG treatment at a stable dose * For female patients of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab.
Exclusion criteria
* History of thymectomy within 12 months prior to screening * Ocular MG (MGFA Class I) and myasthenic crisis (MGFA Class V) within the last 3 months prior to screening * Known disease other than gMG that would interfere with the course and conduct of the study * Positive screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) * Evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection) * Receipt of live or live attenuated vaccine within 6 weeks prior to baseline * Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the last dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the AChR+ Population | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24 | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders. |
| DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24 | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders. |
| DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24 | At Week 24 | The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity. |
| DB Period: Mean Change From Baseline in QMG Score in OP at Week 24 | At Week 24 | The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity. |
| DB Period: Mean Change From Baseline in Myasthenia Gravis Quality of Life 15 Scale (Revised) (MG-QOL 15r) Total Score in AChR+ Population at Week 24 | At Week 24 | The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items were scored on a scale from 0=Not at all to 2=Very much with the total score ranging from 0 to 30 and higher scores indicate worse health-related quality of life (HRQoL). |
| DB Period: Mean Change From Baseline in MG-QOL 15r Total Score in OP at Week 24 | At Week 24 | The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items are scored on a scale from 0=Not at all to 2=Very much, with the total score ranging from 0 to 30 and higher scores indicate worse HRQoL. |
| DB Period: Mean Change From Baseline in Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale Total Score in AChR+ Population at Week 24 | At Week 24 | The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue. |
| DB Period: Mean Change From Baseline in Neuro-QoL Fatigue Subscale Total Score in OP at Week 24 | At Week 24 | The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue. |
| DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24 | At Week 24 | The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity. |
| DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24 | At Week 24 | The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity. |
| DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24 | At Week 24 | The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity. |
| DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24 | At Week 24 | The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity. |
| DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24 | At Week 24 | The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity. |
| DB Period: Mean Change From Baseline in Total MG-ADL Score in the Overall Population (OP) at Week 24 | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
| DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in AChR+ Population at Week 24 | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
| DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in OP at Week 24 | At Week 24 | The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
| DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in AChR+ Population | Baseline up to Week 24 | gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given. |
| DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in OP | Baseline up to Week 24 | gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given. |
| DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24 | Baseline up to Week 24 | The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy. |
| DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24 | Baseline up to Week 24 | The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy. |
| DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in AChR+ Population | Baseline, Week 24 | The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
| DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in OP | Baseline, Week 24 | The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. |
| DB Period: Number of Participants With Adverse Events (AEs) | Day 1 up to approximately 24 weeks | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptoms, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| DB Period: Serum Levels of Interleukin-6 (IL-6) | Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 | — |
| DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24 | — |
| Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab | Baseline to Week 24 | The percentage of ADA-positive participants after drug administration were determined for participants exposed to satralizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. Participants were considered to be ADA-negative if they were ADA-negative or had missing data at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that is at least 4-fold (0.60 titer unit) greater than the titer of the baseline sample. |
| Serum Concentrations of Satralizumab | Weeks 0, 2, 4, 8, 12, 16, 20 and 24 | — |
| DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24 | At Week 24 | The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity. |
Countries
Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, Italy, Japan, Poland, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
A total of 188 participants with generalized myasthenia gravis (gMG) took part in the study across 76 investigational sites in 17 countries. Of the 188, 2 adolescent participants were randomized after the last adult participant was enrolled in the study and therefore were not part of efficacy analysis.
Pre-assignment details
The study consists of 2 periods: Double-blind (DB) period where participants were randomized in a 1:1 ratio to receive either satralizumab or matching placebo and an open-label extension (OLE) period where all participants who completed the DB period received satralizumab. Participants were on a stable dose of background therapy (for gMG) throughout the DB period and until Week 12 of the OLE period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received satralizumab matched placebo, SC, at Weeks 0, 2, 4, and Q4W thereafter until the end of the DB period. | 92 |
| Satralizumab Participants received satralizumab 120 mg or 180 mg, based on body weight, SC, at Weeks 0, 2, 4 (loading doses), and Q4W (maintenance doses) thereafter until the end of the DB period. | 96 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Period (24 Weeks) | Adverse Event | 1 | 2 | 0 | 0 |
| Double-Blind Period (24 Weeks) | Protocol Violation | 1 | 0 | 0 | 0 |
| Double-Blind Period (24 Weeks) | Reason Not Specified | 0 | 1 | 0 | 0 |
| Double-Blind Period (24 Weeks) | Study Terminated by Sponsor | 2 | 0 | 0 | 0 |
| Double-Blind Period (24 Weeks) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Open Label Extension Period (92 Weeks) | Adverse Event | 0 | 0 | 0 | 1 |
| Open Label Extension Period (92 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Open Label Extension Period (92 Weeks) | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Open Label Extension Period (92 Weeks) | Physician Decision | 0 | 0 | 1 | 1 |
| Open Label Extension Period (92 Weeks) | Pregnancy | 0 | 0 | 1 | 0 |
| Open Label Extension Period (92 Weeks) | Reason Not Specified | 0 | 0 | 0 | 1 |
| Open Label Extension Period (92 Weeks) | Reason Unknown | 0 | 0 | 0 | 1 |
| Open Label Extension Period (92 Weeks) | Study Terminated by Sponsor | 0 | 0 | 82 | 81 |
| Open Label Extension Period (92 Weeks) | Withdrawal by Subject | 0 | 0 | 2 | 6 |
Baseline characteristics
| Characteristic | Satralizumab | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 14.4 | 46.5 years STANDARD_DEVIATION 15.3 | 45.9 years STANDARD_DEVIATION 16.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 54 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 124 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 10 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 59 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 59 Participants | 115 Participants | 56 Participants |
| Sex: Female, Male Female | 63 Participants | 119 Participants | 56 Participants |
| Sex: Female, Male Male | 33 Participants | 69 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 87 | 0 / 9 | 1 / 159 | 0 / 25 |
| other Total, other adverse events | 40 / 92 | 48 / 87 | 8 / 9 | 95 / 159 | 16 / 25 |
| serious Total, serious adverse events | 6 / 92 | 3 / 87 | 0 / 9 | 18 / 159 | 5 / 25 |
Outcome results
Primary
DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the AChR+ Population
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the AChR+ Population | -2.57 score on a scale | Standard Error 0.35 |
| Satralizumab | DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG-ADL) Score in the AChR+ Population | -3.59 score on a scale | Standard Error 0.29 |
p-value: 0.019695% CI: [-1.88, -0.16]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in AChR+ Population
The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: Baseline, Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in AChR+ Population | 7.46 weeks | Standard Error 1 |
| Satralizumab | DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in AChR+ Population | 10.90 weeks | Standard Error 1.05 |
p-value: 0.017995% CI: [0.59, 6.29]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in OP
The duration was the difference in weeks between the two visits defining the start and end (or Week 24) of reduction from baseline. The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: Baseline, Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in OP | 7.29 weeks | Standard Error 0.95 |
| Satralizumab | DB Period: Duration of Meaningful Improvement, Defined as ≥ 2-Point Reduction From Baseline in Total MG-ADL Score in OP | 11.02 weeks | Standard Error 0.98 |
p-value: 0.006695% CI: [1.04, 6.42]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in MG-QOL 15r Total Score in OP at Week 24
The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items are scored on a scale from 0=Not at all to 2=Very much, with the total score ranging from 0 to 30 and higher scores indicate worse HRQoL.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in MG-QOL 15r Total Score in OP at Week 24 | -4.73 score on a scale | Standard Error 0.65 |
| Satralizumab | DB Period: Mean Change From Baseline in MG-QOL 15r Total Score in OP at Week 24 | -6.13 score on a scale | Standard Error 0.63 |
p-value: 0.099995% CI: [-3.05, 0.27]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Myasthenia Gravis Quality of Life 15 Scale (Revised) (MG-QOL 15r) Total Score in AChR+ Population at Week 24
The MG-QOL-15r is a disease-specific health-related QoL measure that consists of 15 items: mobility (9 items), symptoms (3 items), and contentment and emotional well-being (3 items). Items were scored on a scale from 0=Not at all to 2=Very much with the total score ranging from 0 to 30 and higher scores indicate worse health-related quality of life (HRQoL).
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Myasthenia Gravis Quality of Life 15 Scale (Revised) (MG-QOL 15r) Total Score in AChR+ Population at Week 24 | -4.69 score on a scale | Standard Error 0.71 |
| Satralizumab | DB Period: Mean Change From Baseline in Myasthenia Gravis Quality of Life 15 Scale (Revised) (MG-QOL 15r) Total Score in AChR+ Population at Week 24 | -6.20 score on a scale | Standard Error 0.69 |
p-value: 0.109495% CI: [-3.36, 0.34]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Neuro-QoL Fatigue Subscale Total Score in OP at Week 24
The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Neuro-QoL Fatigue Subscale Total Score in OP at Week 24 | -3.45 score on a scale | Standard Error 0.83 |
| Satralizumab | DB Period: Mean Change From Baseline in Neuro-QoL Fatigue Subscale Total Score in OP at Week 24 | -5.56 score on a scale | Standard Error 0.69 |
p-value: 0.038295% CI: [-4.1, -0.11]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in QMG Score in OP at Week 24
The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in QMG Score in OP at Week 24 | -1.74 score on a scale | Standard Error 0.43 |
| Satralizumab | DB Period: Mean Change From Baseline in QMG Score in OP at Week 24 | -3.42 score on a scale | Standard Error 0.39 |
p-value: 0.003495% CI: [-2.8, -0.56]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale Total Score in AChR+ Population at Week 24
The Neuro-QoL is a validated tool designed to evaluate the HRQoL in participants with chronic neurological disease. The Fatigue Subscale is implemented as an eight-item, stand-alone short form that assesses the multi-dimensional aspects of fatigue ranging from general tiredness to debilitating exhaustion that Impacts activities of daily living. Each item was assessed using a 5-level Likert scale ranging between 1=never to 5=always. Raw scores range from 8 to 40, higher values indicate greater fatigue.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale Total Score in AChR+ Population at Week 24 | -3.29 score on a scale | Standard Error 0.9 |
| Satralizumab | DB Period: Mean Change From Baseline in Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale Total Score in AChR+ Population at Week 24 | -5.50 score on a scale | Standard Error 0.75 |
p-value: 0.045695% CI: [-4.36, -0.04]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24
The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24 | -1.78 score on a scale | Standard Error 0.46 |
| Satralizumab | DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24 | -3.41 score on a scale | Standard Error 0.41 |
p-value: 0.006295% CI: [-2.8, -0.46]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Total MG-ADL Score in the Overall Population (OP) at Week 24
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: At Week 24
Population: Modified intent-to-treat (mIIT) population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Total MG-ADL Score in the Overall Population (OP) at Week 24 | -2.52 score on a scale | Standard Error 0.32 |
| Satralizumab | DB Period: Mean Change From Baseline in Total MG-ADL Score in the Overall Population (OP) at Week 24 | -3.54 score on a scale | Standard Error 0.28 |
p-value: 0.012395% CI: [-1.82, -0.22]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24
The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24 | -4.18 score on a scale | Standard Error 0.57 |
| Satralizumab | DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24 | -7.18 score on a scale | Standard Error 0.55 |
p-value: <0.000195% CI: [-4.47, -1.53]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24
The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24 | -4.14 score on a scale | Standard Error 0.62 |
| Satralizumab | DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24 | -7.13 score on a scale | Standard Error 0.58 |
p-value: 0.000295% CI: [-4.57, -1.41]ANCOVA and Conditional Mean Imputation
Secondary
DB Period: Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptoms, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Day 1 up to approximately 24 weeks
Population: Safety-evaluable (SE) population included all enrolled participants who received at least one dose of study drug, with participants grouped according to treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | DB Period: Number of Participants With Adverse Events (AEs) | 67 Participants |
| Satralizumab | DB Period: Number of Participants With Adverse Events (AEs) | 78 Participants |
| Satralizumab 180mg | DB Period: Number of Participants With Adverse Events (AEs) | 8 Participants |
Secondary
DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24
The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy.
Time frame: Baseline up to Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24 | 13.8 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24 | 7.0 percentage of participants |
p-value: 0.131495% CI: [-17.25, 3.7]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24
The percentage of participants receiving rescue therapy during DBP analyzed the variable that encodes whether a participant received rescue therapy during DBP or not. If a participant stopped the study drug but received rescue therapy during the safety follow-up and this occurred within 24 weeks of baseline then this was counted as having received rescue therapy.
Time frame: Baseline up to Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24 | 12.4 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24 | 7 percentage of participants |
p-value: 0.226495% CI: [-14.74, 4.61]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in AChR+ Population at Week 24
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in AChR+ Population at Week 24 | 12.5 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in AChR+ Population at Week 24 | 14.0 percentage of participants |
p-value: 0.84795% CI: [-19.4, 15.9]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in OP at Week 24
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in OP at Week 24 | 12.4 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG-ADL Score of 0 or 1) in OP at Week 24 | 15.6 percentage of participants |
p-value: 0.44195% CI: [-15.4, 6.7]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24 | 58.8 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24 | 70.9 percentage of participants |
Comparison: Stratified Analysisp-value: 0.08895% CI: [-27.3, 1.9]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24
The MG-ADL scale was used to assess the degree of gMG symptoms (six items: diplopia, ptosis, difficulties with chewing, swallowing, talking, and respiratory problems) and functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair and impairment in the ability to arise from a chair) that are present and clinically relevant in gMG participants. Each of the eight items was ranked on a 0-3 scale, with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. The total MG-ADL score was calculated as the sum of each item score, with a maximum score ranging from 0 (least severe symptoms/impairment) to 24 (most severe symptoms/impairment). Higher scores indicate greater disease severity. Participants who received rescue therapy were considered non-responders.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24 | 60.7 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24 | 69.8 percentage of participants |
Comparison: Stratified Analysisp-value: 0.13795% CI: [-24.2, 3.3]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24
The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24 | 28.7 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24 | 47.7 percentage of participants |
p-value: 0.01395% CI: [-33.5, -3.9]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24
The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. The 13-items are: ptosis, diplopia, orbicularis oculi weakness, swallowing, speech disruption, percent forced vital capacity, arm and leg endurance (four items), grip strength (two items), and neck flexion strength. Each of the 13 item was quantitatively assessed and scored on a scale from 0=None to 3=Severe, providing a total QMG score (sum of each item score) ranging from 0 to 39 where higher scores indicate greater disease severity.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24 | 28.1 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24 | 50.0 percentage of participants |
p-value: 0.00295% CI: [-36.2, -7.9]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24
The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
Time frame: At Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24 | 55.0 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24 | 75.6 percentage of participants |
p-value: 0.00495% CI: [-35.4, -6.6]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24
The MGC is a composite measure consisting of items drawn from the MG-ADL (chewing, swallowing, speech, and breathing), QMG (diplopia and ptosis), and Manual Muscle Test (hip flexion strength, neck, facial, and shoulder abduction) in an effort to include both clinician- and participant-reported elements in a single measure. Each of the ten items contribute to a total score ranging from 0 to 50, with higher values indicating greater disease severity.
Time frame: At Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24 | 57.3 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24 | 76.0 percentage of participants |
p-value: 0.00595% CI: [-32.8, -5.9]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in AChR+ Population
gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given.
Time frame: Baseline up to Week 24
Population: AChR+ population included all participants in the study who were AChR+.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in AChR+ Population | 17.5 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in AChR+ Population | 9.3 percentage of participants |
p-value: 0.11595% CI: [-2.1, 19]Cochran-Mantel-Haenszel
Secondary
DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in OP
gMG-related exacerbation was defined as one of the following: MG crisis; Substantial symptomatic worsening that requires immediate therapy; or health in jeopardy if rescue therapy is not given.
Time frame: Baseline up to Week 24
Population: mIIT population included all participants that were part of the ITT and had a baseline and at least one post-baseline MG-ADL assessment during the DB period. This excludes adolescents who joined the study after the last adult participant was randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in OP | 16.9 percentage of participants |
| Satralizumab | DB Period: Percentage of Participants With at Least One gMG-Related Exacerbation Between Baseline and Week 24 in OP | 8.3 percentage of participants |
p-value: 0.07795% CI: [-1, 18.6]Cochran-Mantel-Haenszel
Secondary
DB Period: Serum Levels of Interleukin-6 (IL-6)
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24
Population: SE Population included all enrolled participants who received at least one dose of study drug, with participants grouped according to treatment received. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Baseline | 1.97 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 70.7 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 2 | 2.30 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 90.8 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 4 | 2.10 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 81 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 8 | 2.37 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 92.3 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 12 | 2.11 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 78.3 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 16 | 2.17 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 91 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 20 | 2.24 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 93.4 |
| Placebo | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 24 | 2.18 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 99.5 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 16 | 18.02 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 100.2 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 12 | 16.59 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 93 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 2 | 17.45 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 100.6 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 24 | 15.75 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 95.7 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 20 | 15.50 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 112.7 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 8 | 19.40 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 100.8 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 4 | 20.31 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 119.7 |
| Satralizumab | DB Period: Serum Levels of Interleukin-6 (IL-6) | Baseline | 2.19 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 79.3 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 20 | 2.96 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 98.7 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 4 | 2.66 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 63.3 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 8 | 2.46 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 84.5 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 12 | 3.90 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 81.4 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 16 | 2.65 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 71.8 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 24 | 2.26 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 77.1 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Baseline | 3.65 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 124.3 |
| Satralizumab 180mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 2 | 3.08 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 118.5 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 4 | 46.49 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 87.1 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 8 | 38.59 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 37.9 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 2 | 35.23 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 91.8 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Baseline | 4.87 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 87.7 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 12 | 41.72 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 45.5 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 24 | 29.57 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 161.2 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 20 | 26.10 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 220.1 |
| Satralizumab 180 mg | DB Period: Serum Levels of Interleukin-6 (IL-6) | Week 16 | 30.13 nanograms/milliliters (ng/mL) | Geometric Coefficient of Variation 67.1 |
Secondary
DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24
Population: SE Population included all enrolled participants who received at least one dose of study drug, with participants grouped according to treatment received. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Baseline | 36.39 ng/mL | Geometric Coefficient of Variation 27.3 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 2 | 36.08 ng/mL | Geometric Coefficient of Variation 25.8 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 4 | 34.88 ng/mL | Geometric Coefficient of Variation 26 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 8 | 35.26 ng/mL | Geometric Coefficient of Variation 27.9 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 12 | 36.54 ng/mL | Geometric Coefficient of Variation 26.9 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 16 | 35.58 ng/mL | Geometric Coefficient of Variation 25.1 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 20 | 34.58 ng/mL | Geometric Coefficient of Variation 24.6 |
| Placebo | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 24 | 37.46 ng/mL | Geometric Coefficient of Variation 58.7 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 16 | 646.92 ng/mL | Geometric Coefficient of Variation 25.9 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 12 | 643.91 ng/mL | Geometric Coefficient of Variation 26.3 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 2 | 461.84 ng/mL | Geometric Coefficient of Variation 18.1 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 24 | 634.58 ng/mL | Geometric Coefficient of Variation 25.8 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 20 | 637.30 ng/mL | Geometric Coefficient of Variation 23.9 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 8 | 659.47 ng/mL | Geometric Coefficient of Variation 19.4 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 4 | 608.26 ng/mL | Geometric Coefficient of Variation 18.1 |
| Satralizumab | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Baseline | 35.95 ng/mL | Geometric Coefficient of Variation 24.8 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 20 | 33.30 ng/mL | Geometric Coefficient of Variation 24.8 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 4 | 35.65 ng/mL | Geometric Coefficient of Variation 23.3 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 8 | 33.04 ng/mL | Geometric Coefficient of Variation 28.1 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 12 | 33.45 ng/mL | Geometric Coefficient of Variation 26.2 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 16 | 35.80 ng/mL | Geometric Coefficient of Variation 29.6 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 24 | 34.12 ng/mL | Geometric Coefficient of Variation 24.1 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Baseline | 34.52 ng/mL | Geometric Coefficient of Variation 27.9 |
| Satralizumab 180mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 2 | 35.51 ng/mL | Geometric Coefficient of Variation 24 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 4 | 558.11 ng/mL | Geometric Coefficient of Variation 27.3 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 8 | 653.33 ng/mL | Geometric Coefficient of Variation 23.6 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 2 | 441.03 ng/mL | Geometric Coefficient of Variation 32.9 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Baseline | 41.90 ng/mL | Geometric Coefficient of Variation 24.4 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 12 | 646.65 ng/mL | Geometric Coefficient of Variation 25.2 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 24 | 374.27 ng/mL | Geometric Coefficient of Variation 158.9 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 20 | 430.87 ng/mL | Geometric Coefficient of Variation 124.1 |
| Satralizumab 180 mg | DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R) | Week 16 | 600.54 ng/mL | Geometric Coefficient of Variation 40.2 |
Secondary
Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab
The percentage of ADA-positive participants after drug administration were determined for participants exposed to satralizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. Participants were considered to be ADA-negative if they were ADA-negative or had missing data at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that is at least 4-fold (0.60 titer unit) greater than the titer of the baseline sample.
Time frame: Baseline to Week 24
Population: Immunogenicity-analysis population included all participants randomly assigned to study treatment who received any study treatment with at least one post-dose anti-drug antibody (ADA) assessment. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab | Participants with ADA postive sample | 23 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab | Participants with ADA negative sample | 71 Participants |
Secondary
Serum Concentrations of Satralizumab
Time frame: Weeks 0, 2, 4, 8, 12, 16, 20 and 24
Population: Pharmacokinetic (PK)-evaluable population included all participants randomly assigned to study treatment who received at least one dose and had sufficient sampling to permit PK evaluation. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentrations of Satralizumab | Week 4 | 19000 mg | Standard Deviation 8530 |
| Placebo | Serum Concentrations of Satralizumab | Week 12 | 15600 mg | Standard Deviation 9030 |
| Placebo | Serum Concentrations of Satralizumab | Week 0 | NA mg | — |
| Placebo | Serum Concentrations of Satralizumab | Week 16 | 15800 mg | Standard Deviation 9710 |
| Placebo | Serum Concentrations of Satralizumab | Week 8 | 17300 mg | Standard Deviation 9550 |
| Placebo | Serum Concentrations of Satralizumab | Week 20 | 14900 mg | Standard Deviation 9180 |
| Placebo | Serum Concentrations of Satralizumab | Week 24 | 14800 mg | Standard Deviation 10100 |
| Placebo | Serum Concentrations of Satralizumab | Week 2 | 9740 mg | Standard Deviation 5270 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 24 | 14800 mg | Standard Deviation 10900 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 20 | 15100 mg | Standard Deviation 10100 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 0 | NA mg | — |
| Satralizumab | Serum Concentrations of Satralizumab | Week 2 | 9620 mg | Standard Deviation 5210 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 4 | 18900 mg | Standard Deviation 7290 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 8 | 21700 mg | Standard Deviation 9690 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 12 | 19300 mg | Standard Deviation 13000 |
| Satralizumab | Serum Concentrations of Satralizumab | Week 16 | 14500 mg | Standard Deviation 10100 |