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Clinical Trial Results:
A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients with Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)

Summary
EudraCT number	2013-003752-21
Trial protocol	GB DE IT PL HU ES
Global end of trial date	23 Dec 2022

Results information
Results version number	v3(current)
This version publication date	29 Jan 2023
First version publication date	27 Sep 2020
Other versions	v1 , v2
Version creation reason	Correction of full data set Analysis stage correction

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

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Trial information

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Sponsor protocol code

BN40898

ISRCTN number

US NCT number

NCT02028884

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

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

Scientific contact

Medical Communications, Hoffmann-La Roche, 41 616878333, global.trial_information@roche.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001625-PIP01-14

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?

Analysis stage

Final

Date of interim/final analysis

23 Jun 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Dec 2022

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study was to evaluate the efficacy of satralizumab, compared with placebo, in addition to baseline immunosuppressive treatment in participants with neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD).

Protection of trial subjects

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

Background therapy

All patients received azathioprine or mycophenolate mofetil and/or corticosteroids as background therapy

Evidence for comparator

Actual start date of recruitment

20 Feb 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 23

Country: Number of subjects enrolled

Japan: 22

Country: Number of subjects enrolled

Taiwan: 13

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United States: 2

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Ukraine: 3

Country: Number of subjects enrolled

United Kingdom: 3

Worldwide total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants took part in the double-blind (DB) period up to the primary clinical cut-off date (06 June 2018) and in the Open-label Extension Period until the final clinical cut-off date (23-Dec-2021). All ongoing patients have been offered to transition to the WN42349 study

Period 1 title

Double-blind Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo + Baseline Treatment, then Satralizumab

Arm description

Participants received matching placebo, subcutaneous (SC) at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD). At the CCOD, participants who had not experienced a relapse during the DB period were invited to initiate satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Satralizumab + Baseline Treatment, then Satralizumab

Arm description

Participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter throughout the DB period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the CCOD. At the CCOD, participants who had not experienced a relapse during the DB period were invited to continue satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

SA237 - Enrolled in Open-Label

Arm description

In the open-label extension period, the participant received an SC injection of satralizumab at Weeks 0,2, and 4, and Q4W thereafter, in addition to baseline treatment

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Concentrate for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Number of subjects in period 1	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab	SA237 - Enrolled in Open-Label
Started	42	42	1
Completed	32	39	1
Not completed	10	3	0
Consent withdrawn by subject	2	-	-
Adverse event, non-fatal	5	3	-
Eligibility Violation	1	-	-
Non-Compliance With Study Drug	2	-	-

Period 2 title

Open-label Extension Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo + Baseline Treatment, then Satralizumab

Arm description

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Satralizumab + Baseline Treatment, then Satralizumab

Arm description

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

SA237 - Enrolled in Open-Label

Arm description

In the open-label extension period, the participant received an SC injection of satralizumab at Weeks 0,2, and 4, and Q4W thereafter, in addition to baseline treatment

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237 RG6168 RO5333787

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Satralizumab was administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).

Number of subjects in period 2	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab	SA237 - Enrolled in Open-Label
Started	32	39	1
Completed	23	31	1
Not completed	9	8	0
Consent withdrawn by subject	-	6	-
Adverse event, non-fatal	3	1	-
Switched to another treatment option	3	-	-
Refused Treatment/Did Not Cooperate	-	1	-
Lack of efficacy	3	-	-

Baseline characteristics

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Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

SA237 - Enrolled in Open-Label

Reporting group description

In the open-label extension period, the participant received an SC injection of satralizumab at Weeks 0,2, and 4, and Q4W thereafter, in addition to baseline treatment

Reporting group values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab	SA237 - Enrolled in Open-Label	Total
Number of subjects	42	42	1	85
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	3	5	1	9
Adults (18-64 years)	38	34	0	72
From 65-84 years	1	3	0	4
85 years and over	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.4 ± 12.0	40.2 ± 16.3	16.0 ± 0	-
Sex: Female, Male
Units:
Male	2	4	0	6
Female	40	38	1	79
Race/Ethnicity, Customized
Units: Subjects
Not Hispanic or Latino	40	42	1	83
Not Stated	2	0	0	2
Race/Ethnicity, Customized
Units: Subjects
Asian	18	18	0	36
Black or African American	2	0	0	2
White	21	24	0	45
Other	1	0	1	2

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis sets values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment	Satralizumab + Baseline Treatment	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects	42	42	41	34	37	16	13	41	40	75
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.4 ± 12.00	40.2 ± 16.3	±	±	±	±	±	±	±	±
Sex: Female, Male
Units:
Male	2	4
Female	40	38
Race/Ethnicity, Customized
Units: Subjects
Not Hispanic or Latino	40	42
Not Stated	2	0
Race/Ethnicity, Customized
Units: Subjects
Asian	18	18
Black or African American	2	0
White	21	24
Other	1	0

End points

Top of page

Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

SA237 - Enrolled in Open-Label

Reporting group description

In the open-label extension period, the participant received an SC injection of satralizumab at Weeks 0,2, and 4, and Q4W thereafter, in addition to baseline treatment

Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

SA237 - Enrolled in Open-Label

Reporting group description

In the open-label extension period, the participant received an SC injection of satralizumab at Weeks 0,2, and 4, and Q4W thereafter, in addition to baseline treatment

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Placebo + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Satralizumab + Baseline Treatment

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period

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End point title

Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period

End point description

TFR was defined as time from randomization to first occurrence of relapse in the DB period. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD) as adjudicated by an independent clinical endpoint committee (CEC). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onset days that were 30 days of one another, they were counted only as 1 relapse), and onset date used in analysis was the date of first relapse.

End point type

Primary

End point timeframe

Up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: weeks
median (confidence interval 95%)	120.6 (37.0 to 9999)	0000 (0000 to 9999)

Stratified analysis

Statistical analysis description

Stratified by Baseline annualized relapse rate (ARR: 1, > 1) and geographic region (Asia, EU/Other).

Comparison groups

Placebo + Baseline Treatment v Satralizumab + Baseline Treatment

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0184

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

0.88

Secondary: Change from Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period

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End point title

Change from Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period

End point description

The VAS is a subjective measure of pain consisting of a 100 mm line with two endpoints representing 0 = “no pain” and 100 = “pain as bad as it could be”. Participants rated their pain by placing a mark on the line corresponding to their current level of pain. The distance along the line from the “no pain” marker was measured with a ruler giving a pain score out of 100. A higher score indicated more pain and lower scores reflected a better health state. A negative change from baseline indicates an improvement. ANCOVA was used for analysis to report the adjusted mean and standard error (SE).

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard error)
Baseline	34.619 ± 4.026	27.561 ± 4.399
Change from Baseline at Week 24	-3.505 ± 2.357	2.871 ± 2.391

Statistical analysis

Comparison groups

Placebo + Baseline Treatment v Satralizumab + Baseline Treatment

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0602

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.376

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

13.033

Variability estimate

Standard error of the mean

Dispersion value

3.344

Secondary: Change from Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score During the DB Period

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End point title

Change from Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score During the DB Period

End point description

The FACIT Fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. As each of the 13 items of the scale ranges from 0-4, the range of possible scores was computed using FACIT scoring algorithm as 0-52, where 0 is the worst possible score and 52 the best which indicated less fatigue. A positive change from baseline indicates an improvement. ANCOVA was used for analysis to report the adjusted mean and SE.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard error)
Baseline	33.857 ± 1.746	34.732 ± 1.646
Change from Baseline at Week 24	2.234 ± 0.943	0.145 ± 0.963

Statistical analysis

Comparison groups

Placebo + Baseline Treatment v Satralizumab + Baseline Treatment

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1224

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.089

Confidence interval

level

95%

sides

2-sided

lower limit

-4.752

upper limit

0.574

Variability estimate

Standard error of the mean

Dispersion value

1.338

Secondary: Relapse-Free Rate During the DB Period

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End point title

Relapse-Free Rate During the DB Period

End point description

Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onsets within 30 days of one another, they were counted as 1), and onset date used in analysis was the date of first relapse.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	34	37
Units: percentage of participants
number (not applicable)
Week 12	89.86	94.99
Week 24	84.41	88.86
Week 36	69.49	88.86
Week 48	66.02	88.86
Week 72	58.68	81.46
Week 96	58.68	77.58
Week 120	54.17	73.70
Week 144	49.24	73.70
Week 168	43.77	73.70
Week 192	0000	73.70
Week 216	0000	73.70

No statistical analyses for this end point

Secondary: Annualized Relapse Rate (ARR) During the DB Period

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End point title

Annualized Relapse Rate (ARR) During the DB Period

End point description

The ARR is calculated as the total number of participants with relapses experienced divided by the patient-years at risk. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological NMO or NMOSD. Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (2 relapses with onset days in 30 days of one another was counted as 1 relapse), onset date used in analysis was the date of first relapse.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: patients w relapse/patient-years at risk
number (confidence interval 95%)	0.32 (0.19 to 0.51)	0.11 (0.05 to 0.21)

No statistical analyses for this end point

Secondary: Change from Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period

End point description

The mRS is a 7-point disability scale that assesses the degree of disability in participants with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability. A negative change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	1.55 ± 0.97	1.90 ± 1.14
Change from Baseline at Week 24	-0.03 ± 0.42	-0.03 ± 0.50
Change from Baseline at Week 48	-0.18 ± 0.53	-0.13 ± 0.45
Change from Baseline at Week 72	0.07 ± 0.70	0.00 ± 0.52
Change from Baseline at Week 96	0.13 ± 0.62	-0.19 ± 0.51
Change from Baseline at Week 120	-0.10 ± 0.74	-0.05 ± 0.51
Change from Baseline at Week 144	-0.11 ± 0.93	-0.20 ± 0.41
Change from Baseline at Week 168	-0.67 ± 0.58	-0.11 ± 0.33
Change from Baseline at Week 192	0000 ± 0000	-0.50 ± 0.71
Change from Baseline at Week 216	0000 ± 0000	0.00 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period

End point description

The ZBI is the measurement to assess caregiver burden. The 22 items ask for the strain caregivers perceive. Responses range from 0 (never) to 4 (nearly always). The overall ZBI score ranges from 0 to 88. The higher the total score, the heavier the perceived burden. A negative change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 168

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	16	13
Units: score on scale
arithmetic mean (standard deviation)
Baseline	19.31 ± 9.31	18.92 ± 12.82
Change from Baseline at Week 24	-3.44 ± 5.59	-3.57 ± 7.11
Change from Baseline at Week 48	1.17 ± 8.26	1.13 ± 13.45
Change from Baseline at Week 72	2.20 ± 19.64	-0.71 ± 11.60
Change from Baseline at Week 96	3.00 ± 14.98	4.17 ± 13.33
Change from Baseline at Week 120	0.00 ± 3.61	3.40 ± 9.29
Change from Baseline at Week 144	-3.50 ± 12.02	-3.50 ± 11.33
Change from Baseline at Week 168	2.50 ± 13.44	11.00 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period

End point description

The EDSS is an ordinal scale with values from 0 points (normal neurological examination) to 10 points (death) increasing in half-point increments once an EDSS of 1.0 has been reached. Higher scores represent increased disability. A negative change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	41	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	3.63 ± 1.32	3.83 ± 1.57
Change from Baseline at Week 24	-0.21 ± 0.68	-0.14 ± 0.82
Change from Baseline at Week 48	-0.19 ± 0.77	-0.19 ± 0.67
Change from Baseline at Week 72	-0.27 ± 0.68	-0.29 ± 0.73
Change from Baseline at Week 96	-0.19 ± 0.81	-0.19 ± 0.75
Change from Baseline at Week 120	-0.30 ± 0.79	0.03 ± 0.57
Change from Baseline at Week 144	-0.33 ± 0.83	-0.07 ± 0.62
Change from Baseline at Week 168	-0.17 ± 0.76	-0.06 ± 0.58
Change from Baseline at Week 192	0000 ± 0000	0.00 ± 0.71
Change from Baseline at Week 216	0000 ± 0000	-0.50 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period

End point description

Visual acuity was measured using Snellen 20-foot wall chart and then converted to logMAR visual acuity scoring. Lower values indicate better visual acuity. Data are reported for right eye (OD) and left eye (OS). A negative change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: LogMAR units
arithmetic mean (standard deviation)
Baseline: OD	0.490 ± 0.928	0.303 ± 0.593
Baseline: OS	0.526 ± 0.911	0.597 ± 1.016
Change from Baseline at Week 24: OD	-0.064 ± 0.197	0.042 ± 0.236
Change from Baseline at Week 24: OS	-0.012 ± 0.107	0.059 ± 0.319
Change from Baseline at Week 48: OD	-0.019 ± 0.086	0.008 ± 0.093
Change from Baseline at Week 48: OS	0.026 ± 0.096	0.013 ± 0.061
Change from Baseline at Week 72: OD	-0.001 ± 0.110	-0.034 ± 0.111
Change from Baseline at Week 72: OS	-0.001 ± 0.121	-0.019 ± 0.077
Change from Baseline at Week 96: OD	0.018 ± 0.174	-0.013 ± 0.095
Change from Baseline at Week 96: OS	-0.078 ± 0.185	-0.010 ± 0.073
Change from Baseline at Week 120: OD	0.030 ± 0.150	0.011 ± 0.103
Change from Baseline at Week 120: OS	-0.024 ± 0.150	0.014 ± 0.257
Change from Baseline at Week 144: OD	0.058 ± 0.231	-0.016 ± 0.120
Change from Baseline at Week 144: OS	-0.016 ± 0.165	-0.028 ± 0.111
Change from Baseline at Week 168: OD	0.113 ± 0.306	0.027 ± 0.199
Change from Baseline at Week 168: OS	0.100 ± 0.173	-0.024 ± 0.113
Change from Baseline at Week 192: OD	0000 ± 0000	0.150 ± 0.099
Change from Baseline at Week 192: OS	0000 ± 0000	0.000 ± 0.000
Change from Baseline at Week 216: OD	0000 ± 0000	0.120 ± 0000
Change from Baseline at Week 216: OS	0000 ± 0000	0.000 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	44.77 ± 11.08	44.56 ± 9.75
Change from Baseline at Week 24	2.53 ± 7.58	0.57 ± 8.99
Change from Baseline at Week 48	2.78 ± 7.51	-0.61 ± 10.97
Change from Baseline at Week 72	3.47 ± 7.13	2.78 ± 8.13
Change from Baseline at Week 96	5.16 ± 10.52	1.06 ± 7.63
Change from Baseline at Week 120	3.63 ± 8.62	0.71 ± 7.23
Change from Baseline at Week 144	2.83 ± 8.79	3.82 ± 7.15
Change from Baseline at Week 168	2.79 ± 6.85	3.60 ± 9.50
Change from Baseline at Week 192	0000 ± 0000	11.60 ± 7.32
Change from Baseline at Week 216	0000 ± 0000	14.05 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	41.54 ± 9.11	43.60 ± 10.47
Change from Baseline at Week 24	2.79 ± 5.61	1.30 ± 6.01
Change from Baseline at Week 48	0.18 ± 5.33	1.22 ± 5.77
Change from Baseline at Week 72	1.97 ± 6.23	1.16 ± 4.79
Change from Baseline at Week 96	-1.15 ± 7.52	1.88 ± 5.72
Change from Baseline at Week 120	-0.13 ± 7.10	2.34 ± 6.60
Change from Baseline at Week 144	1.78 ± 5.50	3.05 ± 4.23
Change from Baseline at Week 168	0.22 ± 9.23	0.76 ± 5.98
Change from Baseline at Week 192	0000 ± 0000	0.23 ± 0.55
Change from Baseline at Week 216	0000 ± 0000	-1.63 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	43.91 ± 10.22	45.94 ± 11.56
Change from Baseline at Week 24	2.71 ± 7.06	0.03 ± 11.06
Change from Baseline at Week 48	0.81 ± 5.60	0.12 ± 6.99
Change from Baseline at Week 72	3.55 ± 8.20	2.30 ± 6.99
Change from Baseline at Week 96	1.31 ± 7.13	1.15 ± 8.86
Change from Baseline at Week 120	2.22 ± 9.96	-1.45 ± 9.13
Change from Baseline at Week 144	3.58 ± 8.53	3.14 ± 8.18
Change from Baseline at Week 168	1.61 ± 10.58	3.05 ± 9.00
Change from Baseline at Week 192	0000 ± 0000	8.07 ± 0.57
Change from Baseline at Week 216	0000 ± 0000	3.63 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	39.65 ± 7.90	41.23 ± 9.29
Change from Baseline at Week 24	1.84 ± 5.68	-0.60 ± 7.26
Change from Baseline at Week 48	-0.66 ± 5.53	-0.27 ± 6.00
Change from Baseline at Week 72	-0.16 ± 6.25	0.94 ± 5.57
Change from Baseline at Week 96	-1.90 ± 6.17	1.86 ± 6.12
Change from Baseline at Week 120	-0.33 ± 4.03	3.76 ± 6.72
Change from Baseline at Week 144	-0.95 ± 5.66	5.20 ± 7.11
Change from Baseline at Week 168	-5.23 ± 7.41	3.06 ± 6.99
Change from Baseline at Week 192	0000 ± 0000	1.19 ± 5.04
Change from Baseline at Week 216	0000 ± 0000	-2.38 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	43.71 ± 10.92	43.59 ± 10.55
Change from Baseline at Week 24	5.23 ± 7.69	0.99 ± 10.21
Change from Baseline at Week 48	2.76 ± 8.54	0.11 ± 10.73
Change from Baseline at Week 72	5.23 ± 7.66	3.18 ± 9.72
Change from Baseline at Week 96	4.09 ± 8.49	2.12 ± 8.13
Change from Baseline at Week 120	3.14 ± 7.06	1.57 ± 6.76
Change from Baseline at Week 144	3.49 ± 7.04	4.88 ± 8.38
Change from Baseline at Week 168	4.36 ± 3.02	4.07 ± 10.72
Change from Baseline at Week 192	0000 ± 0000	13.09 ± 14.80
Change from Baseline at Week 216	0000 ± 0000	23.55 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	42.50 ± 10.53	43.46 ± 10.34
Change from Baseline at Week 24	3.56 ± 7.04	1.49 ± 7.05
Change from Baseline at Week 48	1.92 ± 4.30	1.86 ± 7.73
Change from Baseline at Week 72	3.19 ± 6.54	0.88 ± 6.52
Change from Baseline at Week 96	0.84 ± 6.77	2.37 ± 7.75
Change from Baseline at Week 120	-0.19 ± 8.39	2.58 ± 6.03
Change from Baseline at Week 144	2.55 ± 4.06	3.32 ± 5.72
Change from Baseline at Week 168	1.92 ± 5.06	0.00 ± 5.50
Change from Baseline at Week 192	0000 ± 0000	1.91 ± 2.70
Change from Baseline at Week 216	0000 ± 0000	1.91 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	43.98 ± 11.46	43.01 ± 10.55
Change from Baseline at Week 24	2.24 ± 10.35	0.36 ± 10.12
Change from Baseline at Week 48	3.29 ± 8.05	0.00 ± 12.49
Change from Baseline at Week 72	1.39 ± 9.38	2.57 ± 7.66
Change from Baseline at Week 96	4.13 ± 14.40	0.83 ± 10.20
Change from Baseline at Week 120	3.13 ± 12.44	0.35 ± 6.95
Change from Baseline at Week 144	3.09 ± 9.61	3.25 ± 7.38
Change from Baseline at Week 168	1.16 ± 5.32	4.64 ± 9.05
Change from Baseline at Week 192	0000 ± 0000	12.19 ± 2.46
Change from Baseline at Week 216	0000 ± 0000	6.97 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	40.74 ± 10.12	41.88 ± 11.38
Change from Baseline at Week 24	3.93 ± 9.56	3.02 ± 6.95
Change from Baseline at Week 48	1.37 ± 7.23	1.40 ± 8.66
Change from Baseline at Week 72	2.40 ± 7.94	2.83 ± 7.81
Change from Baseline at Week 96	0.42 ± 9.03	1.71 ± 4.60
Change from Baseline at Week 120	1.57 ± 9.47	3.14 ± 7.44
Change from Baseline at Week 144	2.99 ± 6.05	2.69 ± 6.80
Change from Baseline at Week 168	3.74 ± 10.61	2.25 ± 6.45
Change from Baseline at Week 192	0000 ± 0000	4.49 ± 6.35
Change from Baseline at Week 216	0000 ± 0000	8.98 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	41.70 ± 11.62	44.26 ± 10.92
Change from Baseline at Week 24	1.73 ± 7.96	0.86 ± 8.69
Change from Baseline at Week 48	1.12 ± 7.80	0.00 ± 10.24
Change from Baseline at Week 72	2.34 ± 7.78	2.18 ± 7.22
Change from Baseline at Week 96	2.82 ± 11.72	0.00 ± 9.38
Change from Baseline at Week 120	1.51 ± 13.59	0.25 ± 9.13
Change from Baseline at Week 144	0.56 ± 9.85	2.01 ± 7.29
Change from Baseline at Week 168	1.67 ± 22.61	0.00 ± 5.61
Change from Baseline at Week 192	0000 ± 0000	0.00 ± 0.00
Change from Baseline at Week 216	0000 ± 0000	-5.01 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline	45.95 ± 9.14	46.66 ± 9.65
Change from Baseline at Week 24	2.66 ± 7.38	1.74 ± 8.61
Change from Baseline at Week 48	1.65 ± 5.60	-0.25 ± 8.71
Change from Baseline at Week 72	4.55 ± 6.91	1.38 ± 9.12
Change from Baseline at Week 96	4.08 ± 8.53	2.41 ± 8.28
Change from Baseline at Week 120	2.97 ± 5.24	2.67 ± 8.45
Change from Baseline at Week 144	3.96 ± 6.12	4.16 ± 10.03
Change from Baseline at Week 168	2.97 ± 2.97	0.99 ± 10.82
Change from Baseline at Week 192	0000 ± 0000	7.43 ± 10.51
Change from Baseline at Week 216	0000 ± 0000	11.89 ± 0000

No statistical analyses for this end point

Secondary: Change from Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period

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End point title

Change from Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period

End point description

The EQ-5D is a participant-answered questionnaire measuring 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with 3 possible response categories: 1) no problems; 2) some problems; 3) severe problems. The scores from 5 dimensions are used as input to generate EQ-5D index score using scoring algorithm. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state. A positive change from baseline indicates an improvement.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	40
Units: score on scale
arithmetic mean (standard deviation)
Baseline	0.7297 ± 0.1863	0.7634 ± 0.1811
Change from Baseline at Week 24	0.0649 ± 0.1596	-0.0082 ± 0.1882
Change from Baseline at Week 48	0.0352 ± 0.1830	0.0011 ± 0.1256
Change from Baseline at Week 72	0.0724 ± 0.2088	0.0241 ± 0.1084
Change from Baseline at Week 96	0.0349 ± 0.1758	0.0167 ± 0.1056
Change from Baseline at Week 120	0.0336 ± 0.2111	0.0257 ± 0.1178
Change from Baseline at Week 144	0.0846 ± 0.1650	0.0488 ± 0.1424
Change from Baseline at Week 168	0.0648 ± 0.1031	0.0307 ± 0.1335
Change from Baseline at Week 192	0000 ± 0000	0.1873 ± 0.2890
Change from Baseline at Week 216	0000 ± 0000	0.3322 ± 0000

No statistical analyses for this end point

Secondary: Serum Satralizumab Concentration During the DB Period

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End point title

Serum Satralizumab Concentration During the DB Period

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 224

End point values	Satralizumab + Baseline Treatment
Number of subjects analysed	41
Units: ng/mL
arithmetic mean (standard deviation)
Baseline	100.00 ± 0.00
Week 2	11343.66 ± 5125.84
Week 4	22222.63 ± 8003.48
Week 5	28461.00 ± 12542.52
Week 6	28174.50 ± 11199.00
Week 8	21246.92 ± 9045.31
Week 12	20927.63 ± 9536.07
Week 16	20274.86 ± 10694.38
Week 20	20146.06 ± 10740.65
Week 24	20189.00 ± 10140.88
Week 28	20826.07 ± 10995.92
Week 32	20631.79 ± 11110.94
Week 36	21114.62 ± 11190.52
Week 40	22224.76 ± 13389.71
Week 44	22582.17 ± 12031.13
Week 48	23324.80 ± 13979.87
Week 52	24570.83 ± 15798.38
Week 56	24252.50 ± 15433.80
Week 60	23061.67 ± 15777.82
Week 64	23369.55 ± 13447.96
Week 68	26194.43 ± 16836.77
Week 72	26618.87 ± 14999.38
Week 76	26539.09 ± 13736.30
Week 80	26868.00 ± 14005.87
Week 84	27037.62 ± 15460.97
Week 88	26203.00 ± 14309.81
Week 92	28308.10 ± 15111.34
Week 96	26754.43 ± 15146.20
Week 100	27707.14 ± 14225.93
Week 104	26203.81 ± 13616.28
Week 108	26112.38 ± 12521.65
Week 112	24925.10 ± 12181.81
Week 116	26360.50 ± 13885.76
Week 120	24910.00 ± 13217.57
Week 124	24689.50 ± 14352.30
Week 128	22395.53 ± 12954.00
Week 132	23804.74 ± 14878.32
Week 136	25856.32 ± 15506.85
Week 140	26118.56 ± 15264.89
Week 144	27975.33 ± 11536.28
Week 148	27935.83 ± 11940.90
Week 152	28967.00 ± 10354.22
Week 156	27990.00 ± 10444.75
Week 160	28983.33 ± 11429.02
Week 164	28903.33 ± 10780.69
Week 168	23683.33 ± 11615.40
Week 172	24498.89 ± 11106.23
Week 176	26300.00 ± 11498.48
Week 180	28300.00 ± 9431.86
Week 184	32380.00 ± 9427.19
Week 188	36600.00 ± 8214.62
Week 192	32650.00 ± 7848.89
Week 196	30800.00 ± 4808.33
Week 200	28400.00 ± 3818.38
Week 204	25300.00 ± 3252.69
Week 208	25900.00 ± 0000
Week 212	17000.00 ± 0000
Week 216	28600.00 ± 0000
Week 220	31600.00 ± 0000
Week 224	28700.00 ± 0000

No statistical analyses for this end point

Secondary: Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period

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End point title

Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: ng/mL
arithmetic mean (standard deviation)
Baseline	32.52 ± 7.78	35.13 ± 21.52
Week 2	33.82 ± 8.30	437.41 ± 72.31
Week 4	33.13 ± 8.52	572.29 ± 94.84
Week 8	34.02 ± 9.43	642.92 ± 115.51
Week 12	32.58 ± 8.52	651.41 ± 99.20
Week 16	32.67 ± 9.32	640.57 ± 97.41
Week 20	34.22 ± 8.15	636.64 ± 109.75
Week 24	34.44 ± 9.31	639.20 ± 108.94
Week 28	33.70 ± 8.28	649.11 ± 131.85
Week 32	33.48 ± 8.74	651.82 ± 162.04
Week 36	34.39 ± 11.01	652.12 ± 124.70
Week 40	33.31 ± 7.86	664.21 ± 158.61
Week 44	33.94 ± 7.77	677.13 ± 173.99
Week 48	34.50 ± 9.14	627.23 ± 217.06
Week 52	44.01 ± 44.26	656.29 ± 173.67
Week 56	37.00 ± 7.42	626.83 ± 155.56
Week 60	36.39 ± 7.81	617.00 ± 142.13
Week 64	35.14 ± 8.78	621.27 ± 152.45
Week 68	35.35 ± 8.68	664.91 ± 130.58
Week 72	36.02 ± 10.73	648.83 ± 134.32
Week 76	36.94 ± 9.46	643.91 ± 118.60
Week 80	36.45 ± 9.50	667.24 ± 133.49
Week 84	34.60 ± 8.88	649.38 ± 137.64
Week 88	31.95 ± 8.29	651.35 ± 150.58
Week 92	34.30 ± 9.71	633.43 ± 134.36
Week 96	32.88 ± 9.39	630.62 ± 162.28
Week 100	33.78 ± 9.04	651.90 ± 162.09
Week 104	31.61 ± 9.13	649.57 ± 185.99
Week 108	31.49 ± 9.23	658.67 ± 152.61
Week 112	32.75 ± 7.77	683.90 ± 135.07
Week 116	33.68 ± 8.31	653.98 ± 194.92
Week 120	33.73 ± 6.20	667.10 ± 152.24
Week 124	33.06 ± 9.31	696.45 ± 138.17
Week 128	34.07 ± 8.83	670.05 ± 138.28
Week 132	34.28 ± 4.95	671.84 ± 138.75
Week 136	32.43 ± 8.12	674.95 ± 170.04
Week 140	32.97 ± 6.52	645.72 ± 132.32
Week 144	35.37 ± 8.91	699.80 ± 101.84
Week 148	37.97 ± 12.40	672.42 ± 107.40
Week 152	35.08 ± 9.08	701.60 ± 110.27
Week 156	36.92 ± 7.77	720.33 ± 103.58
Week 160	40.38 ± 7.31	704.89 ± 109.86
Week 164	43.08 ± 10.54	723.67 ± 136.20
Week 168	42.30 ± 5.92	744.22 ± 123.47
Week 172	42.03 ± 5.87	706.33 ± 127.63
Week 176	39.85 ± 6.15	730.56 ± 121.75
Week 180	38.85 ± 12.09	769.83 ± 119.50
Week 184	0000 ± 0000	736.80 ± 152.09
Week 188	0000 ± 0000	853.67 ± 38.02
Week 192	0000 ± 0000	930.00 ± 49.50
Week 196	0000 ± 0000	887.00 ± 91.92
Week 200	0000 ± 0000	902.50 ± 79.90
Week 204	0000 ± 0000	935.00 ± 7.07
Week 208	0000 ± 0000	941.00 ± 0000
Week 212	0000 ± 0000	971.00 ± 0000
Week 216	0000 ± 0000	896.00 ± 0000
Week 220	0000 ± 0000	901.00 ± 0000
Week 224	0000 ± 0000	831.00 ± 0000

No statistical analyses for this end point

Secondary: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period

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End point title

Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: mg/L
arithmetic mean (standard deviation)
Baseline	1.48 ± 2.08	1.68 ± 2.49
Week 2	1.65 ± 2.86	0.78 ± 2.93
Week 4	1.59 ± 2.27	0.44 ± 0.72
Week 8	1.76 ± 2.25	0.59 ± 1.26
Week 12	1.48 ± 2.07	0.47 ± 0.60
Week 16	1.91 ± 3.34	0.49 ± 0.51
Week 20	1.91 ± 3.44	0.48 ± 0.50
Week 24	2.45 ± 6.87	0.58 ± 0.91
Week 28	1.96 ± 3.24	0.73 ± 1.34
Week 32	2.36 ± 4.96	0.73 ± 1.21
Week 36	2.48 ± 3.59	0.56 ± 0.66
Week 40	2.49 ± 4.53	1.13 ± 2.26
Week 44	1.41 ± 1.47	0.72 ± 1.20
Week 48	1.59 ± 2.07	0.86 ± 1.44
Week 52	2.60 ± 3.87	0.67 ± 0.88
Week 56	1.43 ± 1.58	0.72 ± 1.02
Week 60	2.63 ± 4.34	1.05 ± 2.15
Week 64	11.10 ± 40.09	0.64 ± 0.89
Week 68	1.86 ± 2.66	0.57 ± 0.47
Week 72	3.80 ± 8.83	0.59 ± 0.71
Week 76	5.24 ± 10.68	0.51 ± 0.37
Week 80	2.11 ± 2.63	0.58 ± 0.51
Week 84	2.08 ± 2.26	0.59 ± 0.61
Week 88	5.19 ± 12.83	0.60 ± 0.53
Week 92	2.07 ± 2.21	0.60 ± 0.70
Week 96	2.92 ± 4.60	0.74 ± 1.01
Week 100	2.58 ± 4.53	0.87 ± 1.49
Week 104	1.41 ± 2.05	0.84 ± 1.40
Week 108	1.93 ± 2.25	0.66 ± 0.58
Week 112	1.54 ± 1.56	0.82 ± 0.87
Week 116	2.39 ± 3.91	0.84 ± 1.26
Week 120	1.53 ± 1.33	0.98 ± 1.58
Week 124	1.43 ± 1.43	0.72 ± 0.67
Week 128	6.00 ± 16.28	0.96 ± 1.29
Week 132	1.08 ± 0.94	0.70 ± 0.84
Week 136	1.43 ± 1.54	0.99 ± 1.68
Week 140	1.15 ± 1.28	1.06 ± 2.25
Week 144	0.82 ± 0.73	0.44 ± 0.37
Week 148	1.29 ± 1.43	0.35 ± 0.18
Week 152	1.08 ± 0.97	0.38 ± 0.23
Week 156	1.52 ± 1.42	0.35 ± 0.18
Week 160	0.83 ± 0.53	0.37 ± 0.22
Week 164	3.18 ± 4.89	0.38 ± 0.20
Week 168	0.80 ± 0.26	0.40 ± 0.19
Week 172	1.37 ± 1.00	0.26 ± 0.17
Week 176	0.95 ± 0.64	0.31 ± 0.19
Week 180	30.15 ± 41.65	0.28 ± 0.15
Week 184	0000 ± 0000	0.20 ± 0.11
Week 188	0000 ± 0000	0.37 ± 0.06
Week 192	0000 ± 0000	0.15 ± 0.00
Week 196	0000 ± 0000	0.23 ± 0.11
Week 200	0000 ± 0000	0.23 ± 0.11
Week 204	0000 ± 0000	0.23 ± 0.11
Week 208	0000 ± 0000	0.30 ± 0000
Week 212	0000 ± 0000	0.40 ± 0000
Week 216	0000 ± 0000	0.30 ± 0000
Week 220	0000 ± 0000	0.40 ± 0000
Week 224	0000 ± 0000	0.15 ± 0000

No statistical analyses for this end point

Secondary: Serum Interleukin-6 (IL-6) Concentration During the DB Period

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End point title

Serum Interleukin-6 (IL-6) Concentration During the DB Period

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: pg/mL
arithmetic mean (standard deviation)
Baseline	1.63 ± 0.39	1.92 ± 1.36
Week 2	1.84 ± 0.95	40.12 ± 118.83
Week 4	2.33 ± 2.99	28.30 ± 31.31
Week 8	1.69 ± 0.55	32.37 ± 77.99
Week 12	1.71 ± 0.60	22.95 ± 20.55
Week 16	1.84 ± 0.90	25.76 ± 30.85
Week 20	2.99 ± 5.45	23.07 ± 15.37
Week 24	2.02 ± 1.52	21.53 ± 17.91
Week 28	1.95 ± 1.38	25.14 ± 24.27
Week 32	1.74 ± 0.84	23.77 ± 18.53
Week 36	2.13 ± 1.41	23.08 ± 15.56
Week 40	1.66 ± 0.40	27.31 ± 47.45
Week 44	1.57 ± 0.00	17.01 ± 15.38
Week 48	1.69 ± 0.53	19.45 ± 19.36
Week 52	2.12 ± 1.36	21.11 ± 17.42
Week 56	1.57 ± 0.00	21.74 ± 20.96
Week 60	2.27 ± 1.46	23.25 ± 23.36
Week 64	2.46 ± 3.22	24.31 ± 20.74
Week 68	1.94 ± 1.14	31.30 ± 53.79
Week 72	1.93 ± 0.97	24.69 ± 24.45
Week 76	2.21 ± 1.87	20.45 ± 13.79
Week 80	2.19 ± 2.51	23.29 ± 19.64
Week 84	2.66 ± 2.36	22.71 ± 21.49
Week 88	2.59 ± 2.77	29.17 ± 25.58
Week 92	1.84 ± 0.77	24.51 ± 32.02
Week 96	3.06 ± 3.19	21.52 ± 20.20
Week 100	2.04 ± 1.02	21.77 ± 24.98
Week 104	1.95 ± 0.96	22.61 ± 26.55
Week 108	1.76 ± 0.70	24.18 ± 20.55
Week 112	1.57 ± 0.00	32.18 ± 36.15
Week 116	1.57 ± 0.00	22.33 ± 22.20
Week 120	1.71 ± 0.52	21.86 ± 24.54
Week 124	1.57 ± 0.00	26.23 ± 27.67
Week 128	1.57 ± 0.00	25.40 ± 31.20
Week 132	1.57 ± 0.00	25.48 ± 27.38
Week 136	1.57 ± 0.00	27.23 ± 37.56
Week 140	1.57 ± 0.00	20.66 ± 18.10
Week 144	1.57 ± 0.00	16.82 ± 16.16
Week 148	2.04 ± 1.25	17.10 ± 11.33
Week 152	1.57 ± 0.00	16.62 ± 13.75
Week 156	2.34 ± 1.72	12.67 ± 5.73
Week 160	1.96 ± 0.80	11.15 ± 5.12
Week 164	1.57 ± 0.00	12.84 ± 6.93
Week 168	1.57 ± 0.00	13.30 ± 8.89
Week 172	1.57 ± 0.00	13.89 ± 6.94
Week 176	1.57 ± 0.00	15.11 ± 7.16
Week 180	1.57 ± 0.00	13.34 ± 6.68
Week 184	0000 ± 0000	15.24 ± 9.91
Week 188	0000 ± 0000	13.96 ± 9.74
Week 192	0000 ± 0000	16.71 ± 13.15
Week 196	0000 ± 0000	14.34 ± 12.81
Week 200	0000 ± 0000	18.55 ± 8.84
Week 204	0000 ± 0000	18.24 ± 12.53
Week 208	0000 ± 0000	9.95 ± 0000
Week 212	0000 ± 0000	8.02 ± 0000
Week 216	0000 ± 0000	6.45 ± 0000
Week 220	0000 ± 0000	45.80 ± 0000
Week 224	0000 ± 0000	34.30 ± 0000

No statistical analyses for this end point

Secondary: Number of Participants with at Least One Adverse Event in the DB Period

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End point title

Number of Participants with at Least One Adverse Event in the DB Period

End point description

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.

End point type

Secondary

End point timeframe

Up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: participants	40	37

No statistical analyses for this end point

Secondary: Number of Participants with at Least One Serious Adverse Event in the DB Period

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End point title

Number of Participants with at Least One Serious Adverse Event in the DB Period

End point description

A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.

End point type

Secondary

End point timeframe

Up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: participants	9	7

No statistical analyses for this end point

Secondary: Number of Participants with Non-Serious Adverse Events of Special Interest in the DB Period

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End point title

Number of Participants with Non-Serious Adverse Events of Special Interest in the DB Period

End point description

Non-serious adverse events of special interest for this study included: 1) cases of an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, 2) suspected transmission of an infectious agent by the study treatment.

End point type

Secondary

End point timeframe

Up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: participants	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Selected Adverse Events in the DB Period

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End point title

Number of Participants with Selected Adverse Events in the DB Period

End point description

Selected adverse events for this study included: 1) non-serious infections that required treatments with intravenous (IV) antibiotic, antifungal, antiviral, 2) opportunistic infections that required treatments with oral antibiotics, antifungals, or antivirals, 3) injection-related reactions (IRRs; an AE which occured within 24 hours after study treatment injection except where the event was not considered an allergic reaction), and 4) anaphylaxis (an acute allergic/hypersensitivity reaction).

End point type

Secondary

End point timeframe

Up to Week 224

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	42	41
Units: participants
Non serious Infections requiring IV treatment	4	1
Potential Opportunistic Infections	5	4
Injection Related Reactions	2	5
Anaphylaxis	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period

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End point title

Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period

End point description

The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior.

End point type

Secondary

End point timeframe

Baseline and Post-Baseline (up to Week 224)

End point values	Placebo + Baseline Treatment	Satralizumab + Baseline Treatment
Number of subjects analysed	41	41
Units: participants
Baseline	5	12
Post-Baseline	2	3

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period

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End point title

Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period

End point description

Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during the DB period.

End point type

Secondary

End point timeframe

Up to approximately Week 224

End point values	Satralizumab + Baseline Treatment
Number of subjects analysed	41
Units: percentage
number (not applicable)	41.5

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab Overall S237 period

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End point title

Percentage of Participants with Anti-Drug Antibodies to Satralizumab Overall S237 period

End point description

Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during Overall S237 period. Participants from SAF who received satralizumab were evaluated for this outcome measure. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. Data was summarized together for this outcome measure.

End point type

Secondary

End point timeframe

Up to approximately Week 368

End point values	Satralizumab + Baseline Treatment
Number of subjects analysed	75
Units: Percentage of participants
number (not applicable)
Treatment-Boosted ADA Patients	2.7
Treatment-Induced ADA Patients	44.0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to clinical cut-off date, 23-Dec-2021

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo + Baseline Treatment Double Blind Period

Reporting group description

Participants randomized to this arm for the double-blind period received placebo in addition to baseline treatment. The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26.

Reporting group title

Satralizumab + Baseline Treatment Double Blind period

Reporting group description

Participants randomized to this arm for the double-blind period received satralizumab in addition to baseline treatment. The double-blind period ends when either the participant has a treated relapse or the total number of protocol-defined relapses confirmed by the Clinical Endpoint Committee (CEC) reaches 26.

Reporting group title

Placebo + Baseline Treatment Open Label Period

Reporting group description

In the open-label extension period, the participant received (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter, with the last study drug administration on or before 31 December 2021.

Reporting group title

Satralizumab + Baseline Treatment Open Label period

Reporting group description

Reporting group title

Satralizumab Open-Label Period

Reporting group description

Participant was directly enrolled into the OLE to receive natalizumab. In the open-label extension period, the participant received (with or without baseline treatment) an SC injection of satralizumab at Weeks 0, 2, and 4, and Q4W thereafter.

Serious adverse events	Placebo + Baseline Treatment Double Blind Period	Satralizumab + Baseline Treatment Double Blind period	Placebo + Baseline Treatment Open Label Period	Satralizumab + Baseline Treatment Open Label period	Satralizumab Open-Label Period
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 42 (21.43%)	9 / 42 (21.43%)	5 / 32 (15.63%)	8 / 39 (20.51%)	1 / 1 (100.00%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (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
Breast cancer
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (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
Colon cancer metastatic
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Upper limb fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Forearm fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Tension headache
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parkinsonism
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Neuromyelitis optica pseudo relapse
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Seizure
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
Anaemia macrocytic
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
Immune thrombocytopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
General disorders and administration site conditions
Gait disturbance
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Eye disorders
Glaucoma
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Retinal vein thrombosis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (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
Cataract
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (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
Rectal haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
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
Pancreatitis acute
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Uterine polyp
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
Psychiatric disorders
Suicide attempt
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (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
Systemic lupus erythematosus
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
Cellulitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 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
Hepatitis E
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Influenza
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Urinary tract infection
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Urosepsis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (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
Septic endocarditis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
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	Placebo + Baseline Treatment Double Blind Period	Satralizumab + Baseline Treatment Double Blind period	Placebo + Baseline Treatment Open Label Period	Satralizumab + Baseline Treatment Open Label period	Satralizumab Open-Label Period
Total subjects affected by non serious adverse events
subjects affected / exposed	37 / 42 (88.10%)	35 / 42 (83.33%)	30 / 32 (93.75%)	30 / 39 (76.92%)	1 / 1 (100.00%)
Vascular disorders
Flushing
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	3 / 32 (9.38%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	1	3	2	0
Hypertension
subjects affected / exposed	0 / 42 (0.00%)	3 / 42 (7.14%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	4	2	7	0
Hypotension
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	2 / 32 (6.25%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	1	0	2	0	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	4 / 32 (12.50%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	2	5	0	0
Pyrexia
subjects affected / exposed	5 / 42 (11.90%)	0 / 42 (0.00%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	7	0	1	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	3 / 32 (9.38%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	1	0	5	1	0
Immune system disorders
Hypocomplementaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	5	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	1	0	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 42 (4.76%)	1 / 42 (2.38%)	3 / 32 (9.38%)	3 / 39 (7.69%)	0 / 1 (0.00%)
occurrences all number	3	2	3	3	0
Oropharyngeal pain
subjects affected / exposed	1 / 42 (2.38%)	3 / 42 (7.14%)	2 / 32 (6.25%)	2 / 39 (5.13%)	1 / 1 (100.00%)
occurrences all number	1	4	2	2	1
Rhinorrhoea
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	1	0	3	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	2 / 32 (6.25%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	2	2	2	0
Insomnia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	3 / 32 (9.38%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	0	1	3	1	0
Depression
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	1	2	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	4	1	0	1	0
Lymphocyte count decreased
subjects affected / exposed	2 / 42 (4.76%)	1 / 42 (2.38%)	3 / 32 (9.38%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	2	1	3	1	0
Alanine aminotransferase increased
subjects affected / exposed	2 / 42 (4.76%)	1 / 42 (2.38%)	1 / 32 (3.13%)	5 / 39 (12.82%)	0 / 1 (0.00%)
occurrences all number	2	1	2	5	0
Blood fibrinogen decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0
Blood creatine phosphokinase increased
subjects affected / exposed	2 / 42 (4.76%)	1 / 42 (2.38%)	1 / 32 (3.13%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	3	1	1	1	0
Blood fibrinogen increased
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	0	0	2	0
Blood pressure increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	3	0
Neutrophil count decreased
subjects affected / exposed	0 / 42 (0.00%)	2 / 42 (4.76%)	2 / 32 (6.25%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	2	6	2	1
Prothrombin time prolonged
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0
White blood cell count decreased
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	2 / 32 (6.25%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	1	5	2	1
Blood cholesterol increased
subjects affected / exposed	0 / 42 (0.00%)	2 / 42 (4.76%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	2	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	1	0	2	1
Lymphocyte percentage decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1
Lymphocyte percentage increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	0	0	1	1
Monocyte count increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1
Neutrophil count increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	0	0	2	1
Neutrophil percentage increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	0	0	1	1
Platelet count increased
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	2	0	0	0	1
White blood cell count increased
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	1	0	0	1	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	2	0	2	2	0
Ligament sprain
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	5 / 32 (15.63%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	1	5	0	0
Thermal burn
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	3	1	1	2	0
Rib fracture
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	1	0	2	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	2 / 32 (6.25%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	1	3	2	1	0
Headache
subjects affected / exposed	4 / 42 (9.52%)	10 / 42 (23.81%)	5 / 32 (15.63%)	6 / 39 (15.38%)	1 / 1 (100.00%)
occurrences all number	6	28	8	10	1
Hypoaesthesia
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	3 / 32 (9.38%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	6	0	0
Paraesthesia
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	2	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 42 (11.90%)	3 / 42 (7.14%)	2 / 32 (6.25%)	5 / 39 (12.82%)	0 / 1 (0.00%)
occurrences all number	8	3	2	7	0
Iron deficiency anaemia
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	4 / 32 (12.50%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	1	3	4	2	0
Leukopenia
subjects affected / exposed	4 / 42 (9.52%)	6 / 42 (14.29%)	5 / 32 (15.63%)	4 / 39 (10.26%)	0 / 1 (0.00%)
occurrences all number	12	10	6	10	0
Lymphopenia
subjects affected / exposed	4 / 42 (9.52%)	3 / 42 (7.14%)	1 / 32 (3.13%)	4 / 39 (10.26%)	0 / 1 (0.00%)
occurrences all number	9	7	1	14	0
Neutropenia
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	3	3	1	5	0
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	2 / 32 (6.25%)	3 / 39 (7.69%)	0 / 1 (0.00%)
occurrences all number	0	1	4	3	0
Blepharitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	2 / 32 (6.25%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	1	1	2	1	0
Constipation
subjects affected / exposed	7 / 42 (16.67%)	2 / 42 (4.76%)	2 / 32 (6.25%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	8	2	4	3	0
Dental caries
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	5 / 32 (15.63%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	2	2	5	2	0
Diarrhoea
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	5 / 32 (15.63%)	3 / 39 (7.69%)	1 / 1 (100.00%)
occurrences all number	3	3	5	5	2
Gastritis
subjects affected / exposed	0 / 42 (0.00%)	2 / 42 (4.76%)	2 / 32 (6.25%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	2	3	2	0
Nausea
subjects affected / exposed	3 / 42 (7.14%)	3 / 42 (7.14%)	0 / 32 (0.00%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	3	3	0	0	0
Toothache
subjects affected / exposed	1 / 42 (2.38%)	0 / 42 (0.00%)	4 / 32 (12.50%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	1	0	5	1	0
Abdominal pain
subjects affected / exposed	0 / 42 (0.00%)	2 / 42 (4.76%)	2 / 32 (6.25%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	2	2	0	1
Haemorrhoids
subjects affected / exposed	0 / 42 (0.00%)	2 / 42 (4.76%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	2	0	1	1
Vomiting
subjects affected / exposed	2 / 42 (4.76%)	2 / 42 (4.76%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	2	2	0	1	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 42 (0.00%)	3 / 42 (7.14%)	2 / 32 (6.25%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	0	3	3	1	0
Eczema
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	2 / 32 (6.25%)	3 / 39 (7.69%)	0 / 1 (0.00%)
occurrences all number	1	2	2	3	0
Rash
subjects affected / exposed	2 / 42 (4.76%)	0 / 42 (0.00%)	1 / 32 (3.13%)	2 / 39 (5.13%)	1 / 1 (100.00%)
occurrences all number	2	0	1	4	1
Pruritus
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	1 / 32 (3.13%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	1	1	1	0	1
Renal and urinary disorders
Leukocyturia
subjects affected / exposed	3 / 42 (7.14%)	2 / 42 (4.76%)	1 / 32 (3.13%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	3	2	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 42 (0.00%)	4 / 42 (9.52%)	2 / 32 (6.25%)	3 / 39 (7.69%)	0 / 1 (0.00%)
occurrences all number	0	4	2	3	0
Back pain
subjects affected / exposed	5 / 42 (11.90%)	4 / 42 (9.52%)	1 / 32 (3.13%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	9	4	1	1	0
Myalgia
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	3 / 32 (9.38%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	5	3	2	0
Pain in extremity
subjects affected / exposed	3 / 42 (7.14%)	1 / 42 (2.38%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	3	1	0	2	0
Muscle spasms
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0
Infections and infestations
Cystitis
subjects affected / exposed	4 / 42 (9.52%)	4 / 42 (9.52%)	3 / 32 (9.38%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	6	5	3	3	0
Influenza
subjects affected / exposed	4 / 42 (9.52%)	0 / 42 (0.00%)	4 / 32 (12.50%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	5	0	5	1	0
Nasopharyngitis
subjects affected / exposed	7 / 42 (16.67%)	10 / 42 (23.81%)	11 / 32 (34.38%)	7 / 39 (17.95%)	0 / 1 (0.00%)
occurrences all number	13	22	49	15	0
Oral herpes
subjects affected / exposed	3 / 42 (7.14%)	2 / 42 (4.76%)	4 / 32 (12.50%)	3 / 39 (7.69%)	0 / 1 (0.00%)
occurrences all number	19	6	42	3	0
Pharyngitis
subjects affected / exposed	3 / 42 (7.14%)	4 / 42 (9.52%)	0 / 32 (0.00%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	10	6	0	1	0
Rhinitis
subjects affected / exposed	0 / 42 (0.00%)	3 / 42 (7.14%)	0 / 32 (0.00%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	5	0	1	1
Sinusitis
subjects affected / exposed	0 / 42 (0.00%)	3 / 42 (7.14%)	3 / 32 (9.38%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	4	3	2	0
Upper respiratory tract infection
subjects affected / exposed	6 / 42 (14.29%)	10 / 42 (23.81%)	8 / 32 (25.00%)	8 / 39 (20.51%)	0 / 1 (0.00%)
occurrences all number	12	26	10	36	0
Urinary tract infection
subjects affected / exposed	7 / 42 (16.67%)	6 / 42 (14.29%)	6 / 32 (18.75%)	5 / 39 (12.82%)	0 / 1 (0.00%)
occurrences all number	7	8	16	23	0
Conjunctivitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	1	1	2	0
Hordeolum
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 32 (6.25%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	0	0	2	1	0
Otitis externa
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	2	0	0
Periodontitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	3 / 32 (9.38%)	1 / 39 (2.56%)	0 / 1 (0.00%)
occurrences all number	0	1	6	1	0
Bronchitis
subjects affected / exposed	1 / 42 (2.38%)	2 / 42 (4.76%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	5	1	2	0
Ear infection
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	1 / 32 (3.13%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	1	1	0	2
Gastroenteritis
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	2	8	0	0
Laryngitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 32 (3.13%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	0	0	1	3	0
Localised infection
subjects affected / exposed	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)	0 / 39 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1
Tonsillitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	1 / 32 (3.13%)	1 / 39 (2.56%)	1 / 1 (100.00%)
occurrences all number	0	1	1	1	1
Varicella zoster virus infection
subjects affected / exposed	0 / 42 (0.00%)	1 / 42 (2.38%)	2 / 32 (6.25%)	0 / 39 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	2	0	0
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	1 / 42 (2.38%)	1 / 42 (2.38%)	2 / 32 (6.25%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	1	1	2	2	0
Hypercholesterolaemia
subjects affected / exposed	5 / 42 (11.90%)	4 / 42 (9.52%)	2 / 32 (6.25%)	2 / 39 (5.13%)	0 / 1 (0.00%)
occurrences all number	5	10	2	4	0

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Were there any global substantial amendments to the protocol? Yes

29 Nov 2013

Definition of NMOSD was changed. The population was limited to optic neuritis or transverse myelitis with seropositivity in anti-AQP4 antibody. Adolescent subjects aged 1217 years were allowed to enter the study. Considering the impact of previous treatment on safety and efficacy, the treatment prohibited duration was modified. Methods and duration of contraception were added to exclusion criteria. Because patients with NMO/NMOSD tend to show lower white blood cell value due to baseline treatment with immunosuppressant drugs, the white blood cell exclusion criterion was modified. The protocol v2 was released prior to any patients being enrolled in the study.

27 Feb 2014

Suicidality assessment (C-SSRS) was added as a safety objective per Food and Drug Administration (FDA) request. Based on epidemiologic data, the percentage of patients with negative anti-AQP4 serostatus at screening was capped at 30% in order to reflect the real world population. Further clarifications on the process of screening for potential clinical relapses were added. The roles and responsibilities of the treating and assessing investigator were introduced and the blinding of study and site personnel to certain laboratory parameters were clarified.

18 Dec 2014

The criteria for protocol-defined relapse (PDR) were aligned with another pivotal Phase III study in patients with NMO/NMOSD (study BN40900 / SA309JG/ EudraCT ID 2015-005431-41), which was modified based on FDA's comment. According to the Paediatric Committee’s (PDCO’s) request at least 8 adolescents were to be enrolled. Combination baseline treatment for adolescents was allowed given the low prevalence of pediatric patients and their treatment situation. Additional follow up assessments for adolescents were added. A blood sample collected before screening was accepted for anti-AQP4 antibody screening assessment in case the blood sample at screening was negative for anti-AQP4 antibody, considering the possibility that anti-AQP4 antibody status may change from positive to negative due to treatment for relapse. Permitted relapse treatments and prohibited treatments were modified considering clinical practice. Time limit of relapse evaluation to be recognized as PDR was aligned to another pivotal Phase III study in participants with NMO/NMOSD (study BN40900/SA-309JG// EudraCT ID 2015-005431-41) to avoid incomplete or biased reporting, and relapse assessment procedures were clarified. To avoid missing potential relapses, additional phone calls between visits and instructions to remind participants of possible relapse symptoms were added. The conditions when a participant could move from the double blind (DB) period to the open-label extension (OLE) period were clarified.

03 Jun 2015

Considering the clinical situation where no drugs have been approved for treatment of NMO and NMOSD, the open-label extension period was extended from an ethical point of view. This change was also in alignment with the agreed pediatric investigation plan (PIP). Inclusion of adolescents with negative anti-AQP4 serostatus at screening was allowed.

19 Oct 2015

Clarification that the population which was capped by anti-AQP4 antibody status at screening was limited only to adults.

14 Dec 2016

Addition that adolescents may be enrolled into the OLE period after the total number of PDRs confirmed by the clinical endpoint committee (CEC) reached 26. The minimum number of adolescents (12 to 17 years old) with positive anti- AQP4 serostatus at screening was changed from 6 to 4. The use of satralizumab prefilled syringe (PFS) with needle safety device (NSD) were implemented to be used in the OLE period after the total number of CEC confirmed PDRs reached 26.

17 Apr 2017

The description on the timing of satralizumab PFS with NSD implementation was modified so that satralizumab PFS with NSD could be administered for participants who had already entered into open-label extension period after availability at each study site. The reporting procedure when the medical device (satralizumab PFS with NSD) resulted in an adverse event (AE) to an individual other than the study participant was clarified.

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

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients with Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period

Primary: Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period

Secondary: Change from Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period

Secondary: Change from Baseline at Week 24 in the Visual Analogue Scale (VAS) Score for Pain During the DB Period

Secondary: Change from Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score During the DB Period

Secondary: Change from Baseline at Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score During the DB Period

Secondary: Relapse-Free Rate During the DB Period

Secondary: Relapse-Free Rate During the DB Period

Secondary: Annualized Relapse Rate (ARR) During the DB Period

Secondary: Annualized Relapse Rate (ARR) During the DB Period

Secondary: Change from Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Modified Rankin Scale (mRS) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Zarit Burden Interview (ZBI) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Expanded Disability Status Scale (EDSS) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Visual Acuity (Snellen Chart) at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Short Form Generic Health Survey (SF-36) Mental Component Summary Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Physical Component Summary Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 General Health Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Mental Health Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Physical Functioning Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Role-Emotional Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Role-Physical Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Social Role Functioning Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in SF-36 Vitality Domain Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in EuroQoL-5 Dimensions (EQ-5D) Index Scores at 24 Week Intervals During the DB Period

Secondary: Serum Satralizumab Concentration During the DB Period

Secondary: Serum Satralizumab Concentration During the DB Period

Secondary: Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period

Secondary: Serum Soluble IL-6 Receptor (sIL-6R) Concentration During the DB Period

Secondary: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period

Secondary: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration During the DB Period

Secondary: Serum Interleukin-6 (IL-6) Concentration During the DB Period

Secondary: Serum Interleukin-6 (IL-6) Concentration During the DB Period

Secondary: Number of Participants with at Least One Adverse Event in the DB Period

Secondary: Number of Participants with at Least One Adverse Event in the DB Period

Secondary: Number of Participants with at Least One Serious Adverse Event in the DB Period

Secondary: Number of Participants with at Least One Serious Adverse Event in the DB Period

Secondary: Number of Participants with Non-Serious Adverse Events of Special Interest in the DB Period

Secondary: Number of Participants with Non-Serious Adverse Events of Special Interest in the DB Period

Secondary: Number of Participants with Selected Adverse Events in the DB Period

Secondary: Number of Participants with Selected Adverse Events in the DB Period

Secondary: Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period

Secondary: Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the DB Period

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab Overall S237 period

Secondary: Percentage of Participants with Anti-Drug Antibodies to Satralizumab Overall S237 period

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Addition to Baseline Treatment, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) in Patients with Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)