This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab compared with placebo in participants with generalized myasthenia gravis (gMG).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
188
Satralizumab will be administered as a subcutaneous injection
Satralizumab placebo will be administered as a subcutaneous injection
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
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
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.
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Keck School of Medicine of USC
Los Angeles, California, United States
University of California Irvine - Manchester Pavilion
Orange, California, United States
SC3 Research Group, Inc
Pasadena, California, United States
Medical Faculty Associates Inc.
Washington D.C., District of Columbia, United States
University of Chicago Hospital
Chicago, Illinois, United States
Prairie Education and Research
O'Fallon, Illinois, United States
Hospital Italiano
CABA, Argentina
Hospital Ramos Mejía
CABA, Argentina
Hospital Britanico
Ciudad Autonoma Bs As, Argentina
Fundación Scherbovsky
Mendoza, Argentina
...and 66 more locations
Time frame: At Week 24
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
DB Period: Serum Levels of Interleukin-6 (IL-6)
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24
DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)
Time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24
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
Serum Concentrations of Satralizumab
Time frame: Weeks 0, 2, 4, 8, 12, 16, 20 and 24