Download PDF

Clinical Trial Results:
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of Satralizumab In Patients With Generalized Myasthenia Gravis

Summary
EudraCT number	2020-004436-21
Trial protocol	DK DE NL FR PL IT ES
Global end of trial date	02 Sep 2024

Results information
Results version number	v1
This version publication date	22 Feb 2025
First version publication date	22 Feb 2025
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

WN42636

ISRCTN number

US NCT number

NCT04963270

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4058

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 Sep 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Sep 2024

Was the trial ended prematurely?

Yes

Main objective of the trial

The main objective of the study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of satralizumab compared with placebo in participants with generalized myasthenia gravis (gMG).

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form (ICF).

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Oct 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 39

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

Brazil: 15

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

China: 28

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Denmark: 5

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Italy: 10

Country: Number of subjects enrolled

Japan: 15

Country: Number of subjects enrolled

Korea, Republic of: 9

Country: Number of subjects enrolled

Poland: 28

Country: Number of subjects enrolled

Russian Federation: 2

Country: Number of subjects enrolled

Türkiye: 5

Country: Number of subjects enrolled

Taiwan: 6

Country: Number of subjects enrolled

United States: 9

Worldwide total number of subjects

188

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

156

From 65 to 84 years

85 years and over

Subject disposition

Top of page

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.

Screening details

Study consists of 2 periods: Double-blind (DB) period where participants were randomized in a 1:1 ratio to receive satralizumab or placebo & an open-label extension (OLE) period where all participants who completed DB period received satralizumab. Participants were on a stable dose of background therapy (for gMG) through DB & until Week 12 of OLE.

Period 1 title

Double-Blind Period (24 weeks)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received satralizumab matched placebo, subcutaneously (SC), at Weeks 0, 2, 4, and every 4 weeks (Q4W) thereafter until the end of the DB period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo, SC at Weeks 0, 2, 4 and Q4W thereafter until the end of DB period.

Satralizumab

Arm description

Participants received satralizumab 120 milligrams (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.

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

RO5333787

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who weighed ≤ 100 kilograms (kg) received Satralizumab 120 mg, SC and participants who weighed > 100 kg received Satralizumab 180 mg, SC at Weeks 0, 2, 4 and Q4W thereafter.

Number of subjects in period 1	Placebo	Satralizumab
Started	92	96
Completed	88	92
Not completed	4	4
Adverse Event	1	2
Reason Not Specified	1	1
Withdrawal by Subject	-	1
Study Terminated by Sponsor	2	-

Period 2 title

Open Label Extension Period (92 weeks)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo (DB) to Satralizumab (OLE)

Arm description

After completion of the DB period, participants entered the OLE period where they received satralizumab, 120 mg or 180 mg, based on body weight, SC at Weeks 0, 2, and 4 (loading doses), and Q4W thereafter (maintenance doses) during the OLE period.

Arm type

Experimental

Investigational medicinal product name

RO5333787

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who weighed ≤ 100 kilograms (kg) received Satralizumab 120 mg, SC and participants who weighed > 100 kg received Satralizumab 180 mg, SC at Weeks 0, 2, 4 and Q4W thereafter until the end of OLE period.

Satralizumab (DB) to Satralizumab (OLE)

Arm description

After completion of the DB period, participants entered the OLE period and continued receiving satralizumab 120 mg or 180 mg, based on body weight, SC until the end of the OLE period. Participants received a placebo injection on Week 2 of OLE to maintain blinding to DB treatment assignment.

Arm type

Experimental

Investigational medicinal product name

RO5333787

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who weighed ≤ 100 kilograms (kg) received Satralizumab 120 mg, SC and participants who weighed > 100 kg received Satralizumab 180 mg, SC Q4W until the end of OLE period.

Number of subjects in period 2	Placebo (DB) to Satralizumab (OLE)	Satralizumab (DB) to Satralizumab (OLE)
Started	88	92
Completed	0	0
Not completed	88	92
Physician decision	1	1
Reason Unknown	-	1
Adverse Event	-	1
Reason Not Specified	-	1
Pregnancy	1	-
Withdrawal by Subject	2	6
Study Terminated by Sponsor	82	81
Lost to follow-up	2	-
Lack of efficacy	-	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Participants received satralizumab matched placebo, subcutaneously (SC), at Weeks 0, 2, 4, and every 4 weeks (Q4W) thereafter until the end of the DB period.

Reporting group title

Satralizumab

Reporting group description

Participants received satralizumab 120 milligrams (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.

Reporting group values	Placebo	Satralizumab	Total
Number of subjects	92	96	188
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	2	1	3
Adults (18-64 years)	77	79	156
From 65-84 years	13	16	29
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	45.9 ( 16.3 )	47.0 ( 14.4 )	-
Sex: Female, Male
Units: participants
Female	56	63	119
Male	36	33	69
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	0	1
Asian	27	32	59
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	3	1	4
White	56	59	115
More than one race	1	1	2
Unknown or Not Reported	4	3	7
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	30	24	54
Not Hispanic or Latino	54	70	124
Unknown or Not Reported	8	2	10

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants received satralizumab matched placebo, subcutaneously (SC), at Weeks 0, 2, 4, and every 4 weeks (Q4W) thereafter until the end of the DB period.

Reporting group title

Satralizumab

Reporting group description

Participants received satralizumab 120 milligrams (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.

Reporting group title

Placebo (DB) to Satralizumab (OLE)

Reporting group description

Reporting group title

Satralizumab (DB) to Satralizumab (OLE)

Reporting group description

Subject analysis set title

Placebo Matched to 120 mg Satralizumab

Subject analysis set type

Full analysis

Subject analysis set description

Participants received placebo matched to satralizumab, SC, at Weeks 0, 2, 4, and Q4W thereafter until the end of the DB period.

Subject analysis set title

Satralizumab 120 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received satralizumab 120 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.

Subject analysis set title

Placebo Matched to 180 mg Satralizumab

Subject analysis set type

Full analysis

Subject analysis set description

Participants received placebo matched to satralizumab, SC, at Weeks 0, 2, 4, and Q4W thereafter until the end of the DB period.

Subject analysis set title

Satralizumab 180 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants received satralizumab 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.

Primary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG‑ADL) Score in the AChR+ Population

Top of page

End point title

DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG‑ADL) Score in the AChR+ Population

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Primary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: score on a scale
arithmetic mean (standard error)	-2.57 ( 0.35 )	-3.59 ( 0.29 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0196

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.02

Confidence interval

level

95%

sides

2-sided

lower limit

-1.88

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

0.44

Secondary: DB Period: Mean Change From Baseline in Total MG‑ADL Score in the Overall Population (OP) at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in Total MG‑ADL Score in the Overall Population (OP) at Week 24

End point description

MG-ADL scale was used to assess degree of gMG symptoms (6 items: diplopia, ptosis, difficulties with chewing, swallowing, talking, & respiratory problems) & functional limitations in carrying out activities of daily living (2 items: ability to brush teeth/comb hair & impairment in ability to arise from a chair) that are present & clinically relevant in gMG participants. Each of the 8 items was ranked on a 0-3 scale, with 3=most severe symptoms or impaired performance & 0=no symptoms or impaired performance. 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=greater disease severity. Modified intent-to-treat (mIIT) population=all participants that were part of the ITT & had a baseline & 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: score on a scale
arithmetic mean (standard error)	-2.52 ( 0.32 )	-3.54 ( 0.28 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0123

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.02

Confidence interval

level

95%

sides

2-sided

lower limit

-1.82

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.41

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	58.8 (47.9 to 69.6)	70.9 (61.2 to 80.6)

Placebo vs Satralizumab

Statistical analysis description

Stratified Analysis

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.088

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-12.7

Confidence interval

level

95%

sides

2-sided

lower limit

-27.3

upper limit

1.9

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24

End point description

MG-ADL scale was used to assess degree of gMG symptoms (6 items: diplopia, ptosis, difficulties with chewing, swallowing, talking, & respiratory problems) & functional limitations in carrying out activities of daily living (2 items: ability to brush teeth/comb hair & impairment in ability to arise from a chair) that are present & clinically relevant in gMG participants. Each of the 8 items was ranked on a 0-3 scale, with 3=most severe symptoms or impaired performance & 0=no symptoms or impaired performance. 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=greater disease severity. mIIT population included all participants that were part of the ITT & had a baseline & 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	60.7 (50.4 to 70.9)	69.8 (60.5 to 79)

Placebo vs Satralizumab

Statistical analysis description

Stratified Analysis

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

= 0.137

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-24.2

upper limit

3.3

Secondary: DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: score on a scale
arithmetic mean (standard error)	-1.78 ( 0.46 )	-3.41 ( 0.41 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0062

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.63

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-0.46

Variability estimate

Standard error of the mean

Dispersion value

0.6

Secondary: DB Period: Mean Change From Baseline in QMG Score in OP at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in QMG Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: score on a scale
arithmetic mean (standard error)	-1.74 ( 0.43 )	-3.42 ( 0.39 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0034

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-0.56

Variability estimate

Standard error of the mean

Dispersion value

0.57

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

Top of page

End point title

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

End point description

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). AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: score on a scale
arithmetic mean (standard error)	-4.69 ( 0.71 )	-6.20 ( 0.69 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1094

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-3.36

upper limit

0.34

Variability estimate

Standard error of the mean

Dispersion value

0.94

Secondary: DB Period: Mean Change From Baseline in MG‑QOL 15r Total Score in OP at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in MG‑QOL 15r Total Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: score on a scale
arithmetic mean (standard error)	-4.73 ( 0.65 )	-6.13 ( 0.63 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0999

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-1.39

Confidence interval

level

95%

sides

2-sided

lower limit

-3.05

upper limit

0.27

Variability estimate

Standard error of the mean

Dispersion value

0.85

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

Top of page

End point title

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

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: score on a scale
arithmetic mean (standard error)	-3.29 ( 0.90 )	-5.50 ( 0.75 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0456

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.36

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

1.1

Secondary: DB Period: Mean Change From Baseline in Neuro‑QoL Fatigue Subscale Total Score in OP at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in Neuro‑QoL Fatigue Subscale Total Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: score on a scale
arithmetic mean (standard error)	-3.45 ( 0.83 )	-5.56 ( 0.69 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0382

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

1.02

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24

End point description

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	28.7 (18.7 to 38.8)	47.7 (37 to 58.3)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

= 0.013

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-18.7

Confidence interval

level

95%

sides

2-sided

lower limit

-33.5

upper limit

-3.9

Notes
[1] - Stratified Analysis

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	28.1 (18.7 to 37.5)	50.0 (39.9 to 60.1)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[2]

P-value

= 0.002

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-22

Confidence interval

level

95%

sides

2-sided

lower limit

-36.2

upper limit

-7.9

Notes
[2] - Stratified Analysis

Secondary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: score on a scale
arithmetic mean (standard error)	-4.14 ( 0.62 )	-7.13 ( 0.58 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0002

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-2.99

Confidence interval

level

95%

sides

2-sided

lower limit

-4.57

upper limit

-1.41

Variability estimate

Standard error of the mean

Dispersion value

0.81

Secondary: DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24

Top of page

End point title

DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: score on a scale
arithmetic mean (standard error)	-4.18 ( 0.57 )	-7.18 ( 0.55 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.47

upper limit

-1.53

Variability estimate

Standard error of the mean

Dispersion value

0.75

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24

End point description

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	55.0 (44 to 66)	75.6 (66.4 to 84.7)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-21

Confidence interval

level

95%

sides

2-sided

lower limit

-35.4

upper limit

-6.6

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24

Top of page

End point title

DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	57.3 (46.9 to 67.7)	76.0 (67.4 to 84.6)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

= 0.005

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-19.4

Confidence interval

level

95%

sides

2-sided

lower limit

-32.8

upper limit

-5.9

Notes
[3] - Stratified Analysis

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

Top of page

End point title

DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG‑ADL Score of 0 or 1) in AChR+ Population at Week 24

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	12.5 (-4.8 to 29.8)	14.0 (6.6 to 21.3)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.847

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-19.4

upper limit

15.9

Secondary: DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG‑ADL Score of 0 or 1) in OP at Week 24

Top of page

End point title

DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG‑ADL Score of 0 or 1) in OP at Week 24

End point description

End point type

Secondary

End point timeframe

At Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	12.4 (4.2 to 20.5)	15.6 (8.3 to 22.9)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[4]

P-value

= 0.441

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

-4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

6.7

Notes
[4] - Stratified Analysis

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in AChR+ Population

Top of page

End point title

DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in AChR+ Population

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	17.5 (9.1 to 25.9)	9.3 (3.1 to 15.5)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.115

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in OP

Top of page

End point title

DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in OP

End point description

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. 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.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	16.9 (9 to 24.7)	8.3 (2.8 to 13.9)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[5]

P-value

= 0.077

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Response Rate

Point estimate

8.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

18.6

Notes
[5] - Stratified Analysis

Secondary: DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24

Top of page

End point title

DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24

End point description

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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: percentage of participants
number (confidence interval 95%)	13.8 (5.58 to 21.92)	7.0 (1.01 to 12.94)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1314

Method

Cochran-Mantel-Haenszel

Parameter type

Risk Difference

Point estimate

-6.77

Confidence interval

level

95%

sides

2-sided

lower limit

-17.25

upper limit

3.7

Secondary: DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24

Top of page

End point title

DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24

End point description

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. 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.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: percentage of participants
number (confidence interval 95%)	12.4 (4.96 to 19.76)	7 (1.57 to 13.01)

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[6]

P-value

= 0.2264

Method

Cochran-Mantel-Haenszel

Parameter type

Risk Difference

Point estimate

-5.07

Confidence interval

level

95%

sides

2-sided

lower limit

-14.74

upper limit

4.61

Notes
[6] - Stratified Analysis

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in AChR+ Population

Top of page

End point title

DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in AChR+ Population

End point description

The duration was the difference in weeks between the two visits defining the start & 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, & respiratory problems) & functional limitations in carrying out activities of daily living (two items: ability to brush teeth or comb hair & impairment in the ability to arise from a chair) that are present & 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. AChR+ population included all participants in the study who were AChR+.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	80	86
Units: weeks
arithmetic mean (standard error)	7.46 ( 1.00 )	10.90 ( 1.05 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0179

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

3.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

6.29

Variability estimate

Standard error of the mean

Dispersion value

1.45

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in OP

Top of page

End point title

DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in OP

End point description

Duration was difference in weeks between two visits defining start and end (or Week 24) of reduction from baseline. MG-ADL scale was used to assess degree of gMG symptoms (6 items: diplopia, ptosis, difficulties with chewing, swallowing, talking, & respiratory problems) & functional limitations in carrying out activities of daily living (2 items: ability to brush teeth/comb hair & impairment in ability to arise from a chair) that are present & clinically relevant in gMG participants. Each of the 8 items was ranked on a 0-3 scale, with 3=most severe symptoms or impaired performance & 0=no symptoms or impaired performance. 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 indicates greater disease severity. Modified intent-to-treat (mIIT) population. This excludes adolescents who joined the study after the last adult participant was randomized.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Satralizumab
Number of subjects analysed	89	96
Units: weeks
arithmetic mean (standard error)	7.29 ( 0.95 )	11.02 ( 0.98 )

Placebo vs Satralizumab

Comparison groups

Placebo v Satralizumab

Number of subjects included in analysis

185

Analysis specification

Pre-specified

Analysis type

^[7]

P-value

= 0.0066

Method

ANCOVA and Conditional Mean Imputation

Parameter type

Difference in Adjusted Mean

Point estimate

3.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

6.42

Variability estimate

Standard error of the mean

Dispersion value

1.37

Notes
[7] - Stratified Analysis

Secondary: DB Period: Number of Participants With Adverse Events (AEs)

Top of page

End point title

DB Period: Number of Participants With Adverse Events (AEs) ^[8]

End point description

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. Safety-evaluable (SE) population included all enrolled participants who received at least one dose of study drug, with participants grouped according to treatment received.

End point type

Secondary

End point timeframe

Day 1 up to approximately 24 weeks

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Adverse event data is reported per dose of satralizumab. Hence, subject analysis sets have been used here.

End point values	Placebo	Satralizumab 120 mg	Satralizumab 180 mg
Number of subjects analysed	92	87	9
Units: participants	67	78	8

No statistical analyses for this end point

Secondary: DB Period: Serum Levels of Interleukin-6 (IL-6)

Top of page

End point title

DB Period: Serum Levels of Interleukin-6 (IL-6)

End point description

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. n= number of participants with data available for analyses at the specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24

End point values	Placebo Matched to 120 mg Satralizumab	Satralizumab 120 mg	Placebo Matched to 180 mg Satralizumab	Satralizumab 180 mg
Number of subjects analysed	75	87	16	9
Units: nanograms/milliliters (ng/mL)
geometric mean (geometric coefficient of variation)
Baseline (n=75, 87, 16, 9)	1.97 ( 70.7 )	2.19 ( 79.3 )	3.65 ( 124.3 )	4.87 ( 87.7 )
Week 2 (n=71, 83, 16, 8)	2.30 ( 90.8 )	17.45 ( 100.6 )	3.08 ( 118.5 )	35.23 ( 91.8 )
Week 4 (n=73, 86, 16, 9)	2.10 ( 81.0 )	20.31 ( 119.7 )	2.66 ( 63.3 )	46.49 ( 87.1 )
Week 8 (n=75, 84, 16, 9)	2.37 ( 92.3 )	19.40 ( 100.8 )	2.46 ( 84.5 )	38.59 ( 37.9 )
Week 12 (n=69, 83, 16, 8)	2.11 ( 78.3 )	16.59 ( 93.0 )	3.90 ( 81.4 )	41.72 ( 45.5 )
Week 16 (n=67, 80, 13, 9)	2.17 ( 91.0 )	18.02 ( 100.2 )	2.65 ( 71.8 )	30.13 ( 67.1 )
Week 20 (n=72, 80, 16, 9)	2.24 ( 93.4 )	15.50 ( 112.7 )	2.96 ( 98.7 )	26.10 ( 220.1 )
Week 24 (n=71, 81, 16, 9)	2.18 ( 99.5 )	15.75 ( 95.7 )	2.26 ( 77.1 )	29.57 ( 161.2 )

No statistical analyses for this end point

Secondary: DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)

Top of page

End point title

DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)

End point description

SE Population included all enrolled participants who received at least one dose of study drug, with participants grouped according to treatment received. n= number of participants with data available for analyses at the specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 20 and 24

End point values	Placebo Matched to 120 mg Satralizumab	Satralizumab 120 mg	Placebo Matched to 180 mg Satralizumab	Satralizumab 180 mg
Number of subjects analysed	76	87	16	9
Units: ng/mL
geometric mean (geometric coefficient of variation)
Baseline (n= 76, 87, 16, 9)	36.39 ( 27.3 )	35.95 ( 24.8 )	34.52 ( 27.9 )	41.90 ( 24.4 )
Week 2 (n= 72, 85, 16, 8)	36.08 ( 25.8 )	461.84 ( 18.1 )	35.51 ( 24.0 )	441.03 ( 32.9 )
Week 4 (n= 73, 87, 16, 9)	34.88 ( 26.0 )	608.26 ( 18.1 )	35.65 ( 23.3 )	558.11 ( 27.3 )
Week 8 (n= 75, 87, 16, 9)	35.26 ( 27.9 )	659.47 ( 19.4 )	33.04 ( 28.1 )	653.33 ( 23.6 )
Week 12 (n= 70, 84, 16, 8)	36.54 ( 26.9 )	643.91 ( 26.3 )	33.45 ( 26.2 )	646.65 ( 25.2 )
Week 16 (n= 68, 81, 14, 9)	35.58 ( 25.1 )	646.92 ( 25.9 )	35.80 ( 29.6 )	600.54 ( 40.2 )
Week 20 (n= 73, 82, 16, 9)	34.58 ( 24.6 )	637.30 ( 23.9 )	33.30 ( 24.8 )	430.87 ( 124.1 )
Week 24 (n= 71, 83, 16, 9)	37.46 ( 58.7 )	634.58 ( 25.8 )	34.12 ( 24.1 )	374.27 ( 158.9 )

No statistical analyses for this end point

Secondary: Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab

Top of page

End point title

Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab ^[9]

End point description

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 titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than 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 titer of the baseline sample. Immunogenicity-analysis population was used for analysis. Number of participants analyzed is the number of participants with data available for analyses.

End point type

Secondary

End point timeframe

Baseline to Week 24

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: ADA data is analyzed for participants receiving satralizumab. Hence, the placebo arm is not required here.

End point values	Satralizumab
Number of subjects analysed	94
Units: participants
Participants with ADA postive sample	23
Participants with ADA negative sample	71

No statistical analyses for this end point

Secondary: Serum Concentrations of Satralizumab

Top of page

End point title

Serum Concentrations of Satralizumab

End point description

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. 9999=Geometric Mean and Geometric Coefficient of Variation was not evaluable as samples were below limit of quantification.

End point type

Secondary

End point timeframe

Weeks 0, 2, 4, 8, 12, 16, 20 and 24

End point values	Satralizumab 120 mg	Satralizumab 180 mg
Number of subjects analysed	87	9
Units: mg
arithmetic mean (standard deviation)
Week 0 (n=87, 8)	9999 ( 9999 )	9999 ( 9999 )
Week 2 (n=85, 8)	9740 ( 5270 )	9620 ( 5210 )
Week 4 (n=86, 9)	19000 ( 8530 )	18900 ( 7290 )
Week 8 (n=87, 9)	17300 ( 9550 )	21700 ( 9690 )
Week 12 (n=84, 9)	15600 ( 9030 )	19300 ( 13000 )
Week 16 (n=82, 9)	15800 ( 9710 )	14500 ( 10100 )
Week 20 (n=82, 9)	14900 ( 9180 )	15100 ( 10100 )
Week 24 (n=83, 9)	14800 ( 10100 )	14800 ( 10900 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

DB Period Arms: Day 1 up to approximately 24 weeks; Satralizumab in DB: Day 1 in DB up to end of OLE (approximately 116 weeks); Placebo in DB: Day 1 in OLE up to end of OLE (approximately 92 weeks)

Adverse event reporting additional description

DB Period: SE Population; All Treated Participants Set=all participants who received atleast 1 dose of satralizumab in DB &OLE. As pre-specified in SAP, AEs were reported for DB & OST period. OST=data for all participants from 1st dose of satralizumab (in DB for participants receiving satralizumab &in OLE for participants receiving placebo in DB).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

DB Period: Placebo

Reporting group description

Participants received satralizumab matched placebo, SC, at Weeks 0, 2, 4, and Q4W thereafter until the end of the DB period.

Reporting group title

DB Period: Satralizumab 120mg

Reporting group description

Participants received satralizumab 120 mg, SC, at Weeks 0, 2, 4 (loading doses), and Q4W (maintenance doses) thereafter until the end of the DB period.

Reporting group title

DB Period: Satralizumab 180mg

Reporting group description

Participants received satralizumab 180 mg, SC, at Weeks 0, 2, 4 (loading doses), and Q4W (maintenance doses) thereafter until the end of the DB period.

Reporting group title

Overall Satralizumab 120mg

Reporting group description

Participants who received satralizumab 120 mg, SC, at Weeks 0, 2, 4 (loading doses), and Q4W (maintenance doses) thereafter until the end of the DB period continued receiving satralizumab 120 mg, Q4W in the OLE period. Participants who received placebo in the DB period received satralizumab, 120 mg at Weeks 0, 2, and 4 (loading doses), and Q4W thereafter (maintenance doses) in the OLE period. Participants continuing satralizumab treatment from the DB period received a placebo injection on Week 2 of OLE to maintain blinding to DB treatment assignment.

Reporting group title

Overall Satralizumab 180mg

Reporting group description

Participants who received satralizumab 180 mg, SC, at Weeks 0, 2, 4 (loading doses), and 4 Q4W (maintenance doses) thereafter until the end of the DB period continued receiving satralizumab 180 mg, Q4W in the OLE period. Participants who received placebo in the DB period received satralizumab, 180 mg at Weeks 0, 2, and 4 (loading doses), and Q4W thereafter (maintenance doses) in the OLE period. Participants continuing satralizumab treatment from the DB period received a placebo injection on Week 2 of OLE to maintain blinding to DB treatment assignment.

Serious adverse events	DB Period: Placebo	DB Period: Satralizumab 120mg	DB Period: Satralizumab 180mg	Overall Satralizumab 120mg	Overall Satralizumab 180mg
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 92 (6.52%)	3 / 87 (3.45%)	0 / 9 (0.00%)	18 / 159 (11.32%)	5 / 25 (20.00%)
number of deaths (all causes)	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0
Investigations
Lipase increased
subjects affected / exposed	0 / 92 (0.00%)	1 / 87 (1.15%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Post procedural haemorrhage
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Myasthenia gravis crisis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated inguinal hernia
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Liver disorder
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rosacea
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Infective tenosynovitis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic sinusitis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	2 / 92 (2.17%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurological infection
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 92 (0.00%)	1 / 87 (1.15%)	0 / 9 (0.00%)	2 / 159 (1.26%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 92 (0.00%)	1 / 87 (1.15%)	0 / 9 (0.00%)	1 / 159 (0.63%)	0 / 25 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	DB Period: Placebo	DB Period: Satralizumab 120mg	DB Period: Satralizumab 180mg	Overall Satralizumab 120mg	Overall Satralizumab 180mg
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 92 (43.48%)	48 / 87 (55.17%)	8 / 9 (88.89%)	95 / 159 (59.75%)	16 / 25 (64.00%)
Vascular disorders
Hypertension
subjects affected / exposed	4 / 92 (4.35%)	4 / 87 (4.60%)	1 / 9 (11.11%)	9 / 159 (5.66%)	2 / 25 (8.00%)
occurrences all number	5	4	1	10	2
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	1 / 9 (11.11%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	1	0	1
Psychiatric disorders
Insomnia
subjects affected / exposed	2 / 92 (2.17%)	3 / 87 (3.45%)	0 / 9 (0.00%)	8 / 159 (5.03%)	0 / 25 (0.00%)
occurrences all number	4	3	0	8	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 92 (2.17%)	2 / 87 (2.30%)	1 / 9 (11.11%)	10 / 159 (6.29%)	3 / 25 (12.00%)
occurrences all number	3	2	1	13	4
Platelet count decreased
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	1 / 9 (11.11%)	2 / 159 (1.26%)	1 / 25 (4.00%)
occurrences all number	0	0	1	2	1
Weight increased
subjects affected / exposed	1 / 92 (1.09%)	4 / 87 (4.60%)	0 / 9 (0.00%)	8 / 159 (5.03%)	0 / 25 (0.00%)
occurrences all number	1	4	0	8	0
Injury, poisoning and procedural complications
Intercepted medication error
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	2 / 25 (8.00%)
occurrences all number	0	0	0	0	2
Nervous system disorders
Headache
subjects affected / exposed	9 / 92 (9.78%)	9 / 87 (10.34%)	0 / 9 (0.00%)	20 / 159 (12.58%)	1 / 25 (4.00%)
occurrences all number	17	16	0	40	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 92 (1.09%)	2 / 87 (2.30%)	0 / 9 (0.00%)	2 / 159 (1.26%)	2 / 25 (8.00%)
occurrences all number	1	2	0	2	2
Eye disorders
Diplopia
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	1 / 9 (11.11%)	0 / 159 (0.00%)	1 / 25 (4.00%)
occurrences all number	0	0	1	0	1
Dry eye
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	2 / 9 (22.22%)	2 / 159 (1.26%)	3 / 25 (12.00%)
occurrences all number	0	0	2	2	3
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	2 / 92 (2.17%)	0 / 87 (0.00%)	1 / 9 (11.11%)	1 / 159 (0.63%)	1 / 25 (4.00%)
occurrences all number	2	0	1	1	1
Diarrhoea
subjects affected / exposed	5 / 92 (5.43%)	3 / 87 (3.45%)	1 / 9 (11.11%)	11 / 159 (6.92%)	1 / 25 (4.00%)
occurrences all number	7	3	1	11	2
Nausea
subjects affected / exposed	1 / 92 (1.09%)	4 / 87 (4.60%)	0 / 9 (0.00%)	8 / 159 (5.03%)	0 / 25 (0.00%)
occurrences all number	1	4	0	9	0
Large intestine polyp
subjects affected / exposed	0 / 92 (0.00%)	1 / 87 (1.15%)	1 / 9 (11.11%)	2 / 159 (1.26%)	1 / 25 (4.00%)
occurrences all number	0	1	1	2	1
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	0 / 159 (0.00%)	2 / 25 (8.00%)
occurrences all number	0	0	0	0	2
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 92 (0.00%)	4 / 87 (4.60%)	0 / 9 (0.00%)	8 / 159 (5.03%)	0 / 25 (0.00%)
occurrences all number	0	4	0	8	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	2 / 92 (2.17%)	1 / 87 (1.15%)	1 / 9 (11.11%)	1 / 159 (0.63%)	2 / 25 (8.00%)
occurrences all number	2	1	2	1	3
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 92 (0.00%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	2 / 25 (8.00%)
occurrences all number	0	0	0	1	2
Arthralgia
subjects affected / exposed	6 / 92 (6.52%)	3 / 87 (3.45%)	2 / 9 (22.22%)	6 / 159 (3.77%)	4 / 25 (16.00%)
occurrences all number	7	4	2	7	4
Back pain
subjects affected / exposed	3 / 92 (3.26%)	2 / 87 (2.30%)	0 / 9 (0.00%)	9 / 159 (5.66%)	2 / 25 (8.00%)
occurrences all number	3	2	0	9	2
Myalgia
subjects affected / exposed	3 / 92 (3.26%)	3 / 87 (3.45%)	0 / 9 (0.00%)	6 / 159 (3.77%)	2 / 25 (8.00%)
occurrences all number	4	4	0	7	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	4 / 92 (4.35%)	6 / 87 (6.90%)	0 / 9 (0.00%)	18 / 159 (11.32%)	2 / 25 (8.00%)
occurrences all number	4	6	0	23	4
COVID-19
subjects affected / exposed	7 / 92 (7.61%)	11 / 87 (12.64%)	1 / 9 (11.11%)	22 / 159 (13.84%)	2 / 25 (8.00%)
occurrences all number	7	11	1	24	2
Conjunctivitis
subjects affected / exposed	1 / 92 (1.09%)	0 / 87 (0.00%)	0 / 9 (0.00%)	1 / 159 (0.63%)	2 / 25 (8.00%)
occurrences all number	1	0	0	1	3
Upper respiratory tract infection
subjects affected / exposed	8 / 92 (8.70%)	6 / 87 (6.90%)	0 / 9 (0.00%)	23 / 159 (14.47%)	3 / 25 (12.00%)
occurrences all number	8	7	0	34	5
Pharyngitis
subjects affected / exposed	2 / 92 (2.17%)	5 / 87 (5.75%)	0 / 9 (0.00%)	8 / 159 (5.03%)	1 / 25 (4.00%)
occurrences all number	2	5	0	12	1
Urinary tract infection
subjects affected / exposed	6 / 92 (6.52%)	4 / 87 (4.60%)	1 / 9 (11.11%)	13 / 159 (8.18%)	1 / 25 (4.00%)
occurrences all number	6	5	1	19	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

16 Feb 2021

1. An additional exclusion criterion was added to ensure that participants treated with methotrexate had a washout period of at least 8 weeks before enrolling in this study

10 Nov 2021

1. The sample size for the pharmacokinetic interim analysis was updated so that it was performed when approximately 30 participants had completed a minimum of 8 weeks of DB treatment, with the option to include up to 10 additional participants, if needed, for the independent Data Monitoring Committee (iDMC) to make a decision with regard to dose based upon the adequate precision in the clearance estimate of satralizumab 2. Exclusion criteria pertaining to previous or concomitant therapies and assessments were clarified 3. Information on a new study drug formulation of a 0.5 mL prefilled syringe (PFS) corresponding to 60 mg satralizumab (once available) was included 4. In the OLE period schedule of assessments, the efficacy assessments (Myasthenia Gravis Activities of Daily Living, QMG, MGC, Myasthenia Gravis Quality of Life 15 Scale, Quality of Life in Neurological Disorders Fatigue Subscale, and EuroQoL EQ-5D-5L) was removed from the SFU/end-of-study (EOS) visit

01 Mar 2023

1. The hierarchy of secondary endpoints were included 2. It was clarified that each efficacy analysis will be conducted on all randomized participants that have completed at least one postbaseline MG-ADL assessment 3. The inclusion criterion for participants receiving ongoing gMG treatment at a stable dose was clarified that the dose received cannot exceed the maximum allowed dose 4. The window for Week 4 of the OLE period was corrected from 7 days to 3 days 8. The timing of the collection of serum sample for biomarkers was updated to no longer occur every 24 weeks after Week 24 of the OLE period and to occur during re-loading dose visits 2 and 3

21 Jul 2023

1. The study sample size was reduced from 240 to approximately 185 participants 2. A new section on adolescent enrollment was added to reflect adolescent participant enrollment into the OLE period at study start, and the protocol was revised throughout 3. The pharmacokinetic interim analysis was completed, and the text was revised accordingly 4. Text regarding a China extended enrollment phase was removed as the participant target was reached

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of Satralizumab In Patients With Generalized Myasthenia Gravis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG‑ADL) Score in the AChR+ Population

Primary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Activities of Daily Living (MG‑ADL) Score in the AChR+ Population

Secondary: DB Period: Mean Change From Baseline in Total MG‑ADL Score in the Overall Population (OP) at Week 24

Secondary: DB Period: Mean Change From Baseline in Total MG‑ADL Score in the Overall Population (OP) at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 2-point Reduction From Baseline in Total MG-ADL Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24

Secondary: DB Period: Mean Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score in AChR+ Population at Week 24

Secondary: DB Period: Mean Change From Baseline in QMG Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in QMG Score in OP at Week 24

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

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

Secondary: DB Period: Mean Change From Baseline in MG‑QOL 15r Total Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in MG‑QOL 15r Total Score in OP at Week 24

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

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

Secondary: DB Period: Mean Change From Baseline in Neuro‑QoL Fatigue Subscale Total Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in Neuro‑QoL Fatigue Subscale Total Score in OP at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in QMG Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24

Secondary: DB Period: Mean Change From Baseline in Total Myasthenia Gravis Composite (MGC) Score in AChR+ Population at Week 24

Secondary: DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24

Secondary: DB Period: Mean Change From Baseline in Total MGC Score in OP at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in AChR+ Population at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24

Secondary: DB Period: Percentage of Participants With a ≥ 3-point Reduction From Baseline in Total MGC Score in OP at Week 24

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

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

Secondary: DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG‑ADL Score of 0 or 1) in OP at Week 24

Secondary: DB Period: Percentage of Participants Who Achieved Minimal Symptom Expression (Total MG‑ADL Score of 0 or 1) in OP at Week 24

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in AChR+ Population

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in AChR+ Population

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in OP

Secondary: DB Period: Percentage of Participants With at Least One gMG‑related Exacerbation Between Baseline and Week 24 in OP

Secondary: DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24

Secondary: DB Period: Percentage of Participants in AChR+ Population Receiving Rescue Therapy Between Baseline and Week 24

Secondary: DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24

Secondary: DB Period: Percentage of Participants in OP Receiving Rescue Therapy Between Baseline and Week 24

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in AChR+ Population

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in AChR+ Population

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in OP

Secondary: DB Period: Duration of Meaningful Improvement, Defined as ≥ 2‑point Reduction From Baseline in Total MG‑ADL Score in OP

Secondary: DB Period: Number of Participants With Adverse Events (AEs)

Secondary: DB Period: Number of Participants With Adverse Events (AEs)

Secondary: DB Period: Serum Levels of Interleukin-6 (IL-6)

Secondary: DB Period: Serum Levels of Interleukin-6 (IL-6)

Secondary: DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)

Secondary: DB Period: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6R)

Secondary: Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab

Secondary: Number of Participants With Anti-drug Antibodies (ADAs) to Satralizumab

Secondary: Serum Concentrations of Satralizumab

Secondary: Serum Concentrations of Satralizumab

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate Efficacy, Safety, Pharmacokinetics, And Pharmacodynamics Of Satralizumab In Patients With Generalized Myasthenia Gravis