Download PDF

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)

Summary
EudraCT number	2015-005431-41
Trial protocol	PL RO HR
Global end of trial date	31 Jan 2022

Results information
Results version number	v2(current)
This version publication date	20 Feb 2023
First version publication date	27 Sep 2020
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

BN40900

ISRCTN number

US NCT number

NCT02073279

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche AG

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 AG, 41 616878333, global.trial_information@roche.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

31 Jan 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Jan 2022

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the efficacy of satralizumab monotherapy compared with placebo in participants with NMO and NMOSD. In addition, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of satralizumab were evaluated.

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Aug 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 4

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

Georgia: 1

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Malaysia: 1

Country: Number of subjects enrolled

Poland: 8

Country: Number of subjects enrolled

Turkey: 1

Country: Number of subjects enrolled

Taiwan: 4

Country: Number of subjects enrolled

Ukraine: 10

Country: Number of subjects enrolled

United States: 47

Country: Number of subjects enrolled

Croatia: 1

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Romania: 1

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

Top of page

Recruitment details

The Double-blind (DB) period lasted up to the primary clinical cut-off date (CCOD: 12 Oct 2018) when the study reached 1.5 years since the date of randomization of the last participant enrolled. The Open Label Period lasted up to clinical cut-off date (31-Jan-2022).

Screening details

Participants with neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) were randomized 2:1 to receive either satralizumab 120 mg or matching placebo.

Period 1 title

Double-blind Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

Placebo, then Satralizumab

Arm description

Participants received matching placebo, subcutaneous (SC) injection at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period up to protocol-defined relapse. Following the DB period, all participants received satralizumab 120 mg SC injection 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 (at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

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.

Satralizumab, then Satralizumab

Arm description

Participants received satralizumab 120 mg subcutaneous (SC) injection at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period. Participants who experienced a protocol defined relapse could continue in the Open Label Extension (OLE) period 31 days after relapse. Participants who completed the DB period without relapse could participate in the OLE period 4 weeks after receiving their last dose in the DB period. All OLE participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter.

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

Number of subjects in period 1	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Started	32	63
Completed	28	56
Not completed	4	7
Consent withdrawn by subject	2	2
Adverse event, non-fatal	1	1
Ongoing in study	1	2
Switched to another treatment	-	1
Protocol deviation	-	1

Period 2 title

Open-label Extension Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo, then Satralizumab

Arm description

Arm type

Placebo

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

Satralizumab, then Satralizumab

Arm description

Arm type

Experimental

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

Number of subjects in period 2	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Started	28	56
Completed	21	41
Not completed	7	15
Consent withdrawn by subject	4	5
Adverse event, non-fatal	1	-
Switched to another treatment	1	4
Lost to follow-up	-	4
Refused Treatment/Did Not Cooperate	-	1
Lack of efficacy	1	-
Protocol deviation	-	1

Baseline characteristics

Top of page

Reporting group title

Placebo, then Satralizumab

Reporting group description

Reporting group title

Satralizumab, then Satralizumab

Reporting group description

Reporting group values	Placebo, then Satralizumab	Satralizumab, then Satralizumab	Total
Number of subjects	32	63	95
Age categorical
Units: Subjects
Adults (18-64 years)	32	62	94
From 65-84 years	0	1	1
Age Continuous
Units: Years
arithmetic mean (standard deviation)	40.5 ( 10.5 )	45.3 ( 12.0 )	-
Sex: Female, Male
Units: Participants
Male	1	17	18
Female	31	46	77

End points

Top of page

Reporting group title

Placebo, then Satralizumab

Reporting group description

Reporting group title

Satralizumab, then Satralizumab

Reporting group description

Reporting group title

Placebo, then Satralizumab

Reporting group description

Reporting group title

Satralizumab, then Satralizumab

Reporting group description

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

Top of page

End point title

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

End point description

TFR is time from randomization to first occurrence of relapse in the DB period. Protocol-defined relapse was occurrence of new/worsening neurological symptoms attributable to NMO/NMOSD. Symptoms persisted for >24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New/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. Intent-to-treat (ITT) population: all randomized participants. 999999=upper limit of CI was not reached due to low number of participants with events. 99999=median was not reached due to low number of participants with events.

End point type

Primary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: weeks
median (confidence interval 95%)	128.3 (29.9 to 999999)	99999 (135.7 to 999999)

Satralizumab versus Placebo

Statistical analysis description

Stratified by prior therapy (B-cell depleting therapy or immunosuppressants/others) and most recent attack (first attack or relapse).

Comparison groups

Placebo, then Satralizumab v Satralizumab, then Satralizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0184

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

0.89

Secondary: Change in Visual Analogue Scale (VAS) for Pain from Baseline to Week 24

Top of page

End point title

Change in Visual Analogue Scale (VAS) for Pain from Baseline to Week 24

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). ITT population included all participants randomized to the treatment groups. Missing data were imputed by BOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard error)
Baseline (n=32, 62)	27.563 ( 5.438 )	31.661 ( 3.665 )
Change from Baseline to Week 24 (n=32, 62)	-5.949 ( 4.832 )	-2.735 ( 4.260 )

Satralizumab versus Placebo

Comparison groups

Placebo, then Satralizumab v Satralizumab, then Satralizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4436 ^[1]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.215

Confidence interval

level

95%

sides

2-sided

lower limit

-5.086

upper limit

11.515

Variability estimate

Standard error of the mean

Dispersion value

4.178

Notes
[1] - ANCOVA model: treatment group as fixed effect and baseline measurements, prior therapy, most recent attack (first attack/relapse) as covariates.

Secondary: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale from Baseline to Week 24

Top of page

End point title

Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale from Baseline to Week 24

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. ITT population included all participants randomized to the treatment groups. Missing data were imputed by BOCF method.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard error)
Baseline (n=32, 62)	29.656 ( 2.280 )	30.590 ( 1.492 )
Change from Baseline to Week 24 (n=32, 62)	3.602 ( 1.820 )	5.709 ( 1.610 )

Satralizumab versus Placebo

Comparison groups

Placebo, then Satralizumab v Satralizumab, then Satralizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1824 ^[2]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.107

Confidence interval

level

95%

sides

2-sided

lower limit

-1.008

upper limit

5.221

Variability estimate

Standard error of the mean

Dispersion value

1.567

Notes
[2] - ANCOVA model: treatment group as fixed effect and baseline measurements, prior therapy, most recent attack (first attack/relapse) as covariates.

Secondary: Relapse-Free Rate During the DB Period

Top of page

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 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. ITT population included all participants randomized to the treatment groups. 6666= 0 participants.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	23	56
Units: percentage
number (not applicable)
Week 12 (n=23, 56)	74.87	88.89
Week 24 (n=22, 54)	71.61	85.71
Week 36 (n=19, 49)	61.85	79.37
Week 48 (n=19, 46)	61.85	76.13
Week 72 (n=13, 43)	51.21	74.40
Week 96 (n=9, 30)	51.21	72.14
Week 120 (n=3, 16)	51.21	72.14
Week 144 (n=2, 12)	34.14	62.80
Week 168 (n=1, 10)	34.14	62.80
Week 192 (n=1, 3)	34.14	62.80
Week 216 (n=1, 0)	34.14	6666

No statistical analyses for this end point

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

Top of page

End point title

Annualized Relapse Rate (ARR) During the DB Period

End point description

The ARR is calculated as the total number participants with relapses experienced divided by the patient-years at risk. Protocol-defined relapse was occurrence of new/worsening neurological symptoms attributable to neurological NMO/NMOSD. Symptoms persisted for >24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New/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. ITT population included all participants randomized to the treatment groups.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: patients w relapse/patient-years at risk
number (confidence interval 95%)	0.41 (0.24 to 0.67)	0.17 (0.10 to 0.26)

No statistical analyses for this end point

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

Top of page

End point title

Change from Baseline in Short Form Generic Health Survey (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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	42.86 ( 11.28 )	43.20 ( 11.08 )
Change from Baseline at Week 24 (n=20, 54)	-0.89 ( 8.35 )	-0.13 ( 8.09 )
Change from Baseline at Week 48 (n=18, 46)	1.75 ( 5.42 )	1.36 ( 8.89 )
Change from Baseline at Week 72 (n=13, 43)	3.19 ( 8.04 )	0.91 ( 9.23 )
Change from Baseline at Week 96 (n=8, 31)	3.43 ( 5.60 )	2.38 ( 7.82 )
Change from Baseline at Week 120 (n=3, 16)	0.00 ( 8.07 )	0.53 ( 6.21 )
Change from Baseline at Week 144 (n=2, 12)	-2.22 ( 8.84 )	2.59 ( 6.66 )
Change from Baseline at Week 168 (n=1, 10)	0.80 ( 9999 )	4.19 ( 7.01 )
Change from Baseline at Week 192 (n=1, 2)	-8.47 ( 9999 )	0 ( 0 )
Change from Baseline at Week 216 (n=1, 0)	-12.50 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 General Health Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	39.43 ( 9.50 )	39.72 ( 10.41 )
Change from Baseline at Week 24 (n=20, 54)	-0.52 ( 9.96 )	0.49 ( 6.46 )
Change from Baseline at Week 48 (n=18, 46)	1.85 ( 9.72 )	1.01 ( 7.61 )
Change from Baseline at Week 72 (n=13, 43)	4.83 ( 12.41 )	3.21 ( 6.57 )
Change from Baseline at Week 96 (n=8, 31)	6.60 ( 9.10 )	3.45 ( 6.42 )
Change from Baseline at Week 120 (n=3, 16)	8.72 ( 13.55 )	3.60 ( 7.02 )
Change from Baseline at Week 144 (n=2, 12)	5.23 ( 14.11 )	2.82 ( 8.00 )
Change from Baseline at Week 168 (n=1, 10)	-7.13 ( 9999 )	5.04 ( 9.45 )
Change from Baseline at Week 192 (n=1, 2)	-4.75 ( 9999 )	8.32 ( 11.77 )
Change from Baseline at Week 216 (n=1, 0)	-4.75 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Mental Health Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	42.86 ( 12.69 )	46.78 ( 10.10 )
Change from Baseline at Week 24 (n=20, 54)	0.79 ( 9.02 )	1.84 ( 7.05 )
Change from Baseline at Week 48 (n=18, 46)	-0.58 ( 7.32 )	2.67 ( 7.89 )
Change from Baseline at Week 72 (n=13, 43)	2.62 ( 6.32 )	1.95 ( 7.85 )
Change from Baseline at Week 96 (n=8, 31)	-3.60 ( 6.08 )	2.36 ( 7.38 )
Change from Baseline at Week 120 (n=3, 16)	-2.62 ( 6.92 )	0.82 ( 10.32 )
Change from Baseline at Week 144 (n=2, 12)	1.31 ( 1.85 )	2.83 ( 9.43 )
Change from Baseline at Week 168 (n=1, 10)	5.23 ( 9999 )	2.62 ( 8.89 )
Change from Baseline at Week 192 (n=1, 2)	-13.08 ( 9999 )	-3.93 ( 12.95 )
Change from Baseline at Week 216 (n=1, 0)	-2.62 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Physical Functioning Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	38.70 ( 12.24 )	39.48 ( 10.99 )
Change from Baseline at Week 24 (n=20, 54)	2.20 ( 4.62 )	1.96 ( 6.12 )
Change from Baseline at Week 48 (n=18, 46)	2.34 ( 6.90 )	3.33 ( 6.76 )
Change from Baseline at Week 72 (n=13, 43)	6.62 ( 9.71 )	2.99 ( 6.94 )
Change from Baseline at Week 96 (n=8, 31)	5.50 ( 9.62 )	3.59 ( 7.49 )
Change from Baseline at Week 120 (n=3, 16)	7.01 ( 8.63 )	1.94 ( 8.05 )
Change from Baseline at Week 144 (n=2, 12)	4.79 ( 9.48 )	3.19 ( 10.87 )
Change from Baseline at Week 168 (n=1, 10)	1.91 ( 9999 )	-0.96 ( 8.62 )
Change from Baseline at Week 192 (n=1, 2)	-1.92 ( 9999 )	4.78 ( 4.06 )
Change from Baseline at Week 216 (n=1, 0)	-3.83 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Role-Emotional Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	42.24 ( 13.09 )	42.07 ( 13.62 )
Change from Baseline at Week 24 (n=20, 54)	-1.57 ( 15.67 )	3.87 ( 11.27 )
Change from Baseline at Week 48 (n=18, 46)	0.78 ( 8.57 )	2.73 ( 10.30 )
Change from Baseline at Week 72 (n=13, 43)	4.55 ( 7.96 )	3.89 ( 9.22 )
Change from Baseline at Week 96 (n=8, 31)	3.05 ( 11.98 )	1.12 ( 11.87 )
Change from Baseline at Week 120 (n=3, 16)	-12.77 ( 14.07 )	1.31 ( 14.04 )
Change from Baseline at Week 144 (n=2, 12)	-12.19 ( 17.23 )	1.74 ( 13.40 )
Change from Baseline at Week 168 (n=1, 10)	0.00 ( 9999 )	-0.35 ( 11.89 )
Change from Baseline at Week 192 (n=1, 2)	-13.93 ( 9999 )	-3.49 ( 4.93 )
Change from Baseline at Week 216 (n=1, 0)	-10.45 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Role-Physical Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	37.86 ( 11.28 )	37.43 ( 11.55 )
Change from Baseline at Week 24 (n=20, 54)	3.14 ( 9.92 )	3.52 ( 8.38 )
Change from Baseline at Week 48 (n=18, 46)	4.12 ( 7.24 )	5.01 ( 8.25 )
Change from Baseline at Week 72 (n=13, 43)	5.70 ( 7.65 )	4.59 ( 8.56 )
Change from Baseline at Week 96 (n=8, 31)	5.62 ( 6.35 )	4.83 ( 8.31 )
Change from Baseline at Week 120 (n=3, 16)	2.25 ( 8.99 )	3.18 ( 9.46 )
Change from Baseline at Week 144 (n=2, 12)	-3.37 ( 11.12 )	2.43 ( 8.80 )
Change from Baseline at Week 168 (n=1, 10)	0.00 ( 9999 )	0.00 ( 9.10 )
Change from Baseline at Week 192 (n=1, 2)	-6.74 ( 9999 )	4.49 ( 6.35 )
Change from Baseline at Week 216 (n=1, 0)	-17.97 ( 9999 )	6666 ( 6666 )

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

Top of page

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

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	42.93 ( 13.22 )	41.01 ( 11.66 )
Change from Baseline at Week 24 (n=20, 54)	1.76 ( 12.42 )	2.42 ( 9.63 )
Change from Baseline at Week 48 (n=18, 46)	0.56 ( 10.59 )	2.62 ( 8.17 )
Change from Baseline at Week 72 (n=13, 43)	0.39 ( 11.66 )	3.96 ( 7.93 )
Change from Baseline at Week 96 (n=8, 31)	0.63 ( 1.77 )	3.56 ( 7.89 )
Change from Baseline at Week 120 (n=3, 16)	-5.01 ( 13.26 )	0.31 ( 8.48 )
Change from Baseline at Week 144 (n=2, 12)	7.52 ( 10.63 )	3.76 ( 14.68 )
Change from Baseline at Week 168 (n=1, 10)	-5.01 ( 9999 )	-1.50 ( 7.86 )
Change from Baseline at Week 192 (n=1, 2)	-5.01 ( 9999 )	-2.51 ( 3.54 )
Change from Baseline at Week 216 (n=1, 0)	0.00 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Vitality Domain 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, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	40.72 ( 11.86 )	46.02 ( 10.58 )
Change from Baseline at Week 24 (n=20, 54)	1.49 ( 10.22 )	2.33 ( 8.29 )
Change from Baseline at Week 48 (n=18, 46)	4.79 ( 9.07 )	4.15 ( 7.49 )
Change from Baseline at Week 72 (n=13, 43)	3.43 ( 9.38 )	3.68 ( 6.43 )
Change from Baseline at Week 96 (n=8, 31)	0.00 ( 7.94 )	4.34 ( 9.39 )
Change from Baseline at Week 120 (n=3, 16)	-1.98 ( 11.24 )	3.96 ( 9.94 )
Change from Baseline at Week 144 (n=2, 12)	-9.41 ( 7.70 )	4.95 ( 7.95 )
Change from Baseline at Week 168 (n=1, 10)	-5.94 ( 9999 )	5.05 ( 6.58 )
Change from Baseline at Week 192 (n=1, 2)	-11.88 ( 9999 )	0.00 ( 8.40 )
Change from Baseline at Week 216 (n=1, 0)	-11.88 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

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

Top of page

End point title

Change from Baseline in 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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	44.03 ( 13.93 )	46.43 ( 11.55 )
Change from Baseline at Week 24 (n=20, 54)	-0.28 ( 11.19 )	2.89 ( 8.96 )
Change from Baseline at Week 48 (n=18, 46)	0.09 ( 8.96 )	2.63 ( 8.04 )
Change from Baseline at Week 72 (n=13, 43)	1.54 ( 8.18 )	3.17 ( 7.70 )
Change from Baseline at Week 96 (n=8, 31)	-2.65 ( 6.05 )	1.91 ( 9.32 )
Change from Baseline at Week 120 (n=3, 16)	-10.65 ( 11.99 )	1.03 ( 12.92 )
Change from Baseline at Week 144 (n=2, 12)	-5.40 ( 8.41 )	2.98 ( 12.99 )
Change from Baseline at Week 168 (n=1, 10)	-0.61 ( 9999 )	1.63 ( 11.86 )
Change from Baseline at Week 192 (n=1, 2)	-14.38 ( 9999 )	-5.88 ( 7.54 )
Change from Baseline at Week 216 (n=1, 0)	-4.22 ( 9999 )	6666 ( 6666 )

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

Top of page

End point title

Change from Baseline in SF-36 Physical 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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	38.89 ( 11.20 )	38.59 ( 9.68 )
Change from Baseline at Week 24 (n=20, 54)	1.78 ( 4.99 )	1.05 ( 6.14 )
Change from Baseline at Week 48 (n=18, 46)	3.57 ( 4.94 )	2.85 ( 4.90 )
Change from Baseline at Week 72 (n=13, 43)	5.68 ( 7.32 )	2.87 ( 6.80 )
Change from Baseline at Week 96 (n=8, 31)	7.25 ( 7.08 )	4.20 ( 5.90 )
Change from Baseline at Week 120 (n=3, 16)	8.95 ( 8.51 )	2.68 ( 8.72 )
Change from Baseline at Week 144 (n=2, 12)	3.18 ( 10.67 )	2.89 ( 7.11 )
Change from Baseline at Week 168 (n=1, 10)	-2.00 ( 9999 )	1.83 ( 10.96 )
Change from Baseline at Week 192 (n=1, 2)	-1.79 ( 9999 )	7.24 ( 3.35 )
Change from Baseline at Week 216 (n=1, 0)	-10.84 ( 9999 )	6666 ( 6666 )

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

Top of page

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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 62)	0.7153 ( 0.2253 )	0.6881 ( 0.2040 )
Change from Baseline at Week 24 (n=20, 53)	0.0031 ( 0.1602 )	0.0188 ( 0.1812 )
Change from Baseline at Week 48 (n=18, 45)	0.0016 ( 0.1176 )	0.0244 ( 0.1571 )
Change from Baseline at Week 72 (n=12, 42)	0.0582 ( 0.1498 )	0.0238 ( 0.1323 )
Change from Baseline at Week 96 (n=8, 30)	0.0447 ( 0.1508 )	0.0460 ( 0.1067 )
Change from Baseline at Week 120 (n=3, 16)	-0.0288 ( 0.1908 )	0.0099 ( 0.1636 )
Change from Baseline at Week 144 (n=2, 12)	-0.1001 ( 0.1416 )	0.0063 ( 0.2299 )
Change from Baseline at Week 168 (n=1, 10)	0.0000 ( 9999 )	-0.0261 ( 0.2532 )
Change from Baseline at Week 192 (n=1, 2)	-0.2002 ( 9999 )	0.0299 ( 0.0423 )
Change from Baseline at Week 216 (n=1, 0)	-0.2002 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

Secondary: Change from Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period

Top of page

End point title

Change from Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period

End point description

The T25W is an assessment of walking ability. The time (in seconds) that the participant took to walk 25 feet was measured. Speed is calculated as 1/Timed 25-Foot Walk where time is measured in seconds. A positive change from baseline indicates an improvement. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	29	63
Units: 1/seconds
arithmetic mean (standard deviation)
Baseline (n=29, 63)	0.1442 ( 0.0793 )	0.1355 ( 0.0561 )
Change from Baseline at Week 24 (n=19, 53)	0.0030 ( 0.0374 )	0.0040 ( 0.0225 )
Change from Baseline at Week 48 (n=16, 45)	0.0142 ( 0.0493 )	0.0115 ( 0.0306 )
Change from Baseline at Week 72 (n=11, 43)	0.0205 ( 0.0531 )	0.0071 ( 0.0257 )
Change from Baseline at Week 96 (n=6, 31)	-0.0031 ( 0.0251 )	0.0081 ( 0.0253 )
Change from Baseline at Week 120 (n=3, 16)	0.0489 ( 0.0301 )	0.0063 ( 0.0386 )
Change from Baseline at Week 144 (n=2, 12)	0.0388 ( 0.0572 )	0.0003 ( 0.0443 )
Change from Baseline at Week 168 (n=1, 9)	-0.0656 ( 9999 )	-0.0155 ( 0.0379 )
Change from Baseline at Week 192 (n=1, 2)	-0.0812 ( 9999 )	-0.0304 ( 0.0360 )
Change from Baseline at Week 216 (n=1, 0)	-0.0917 ( 9999 )	6666 ( 6666 )

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

Top of page

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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 63)	1.66 ( 1.00 )	1.97 ( 0.98 )
Change from Baseline at Week 24 (n=19, 54)	-0.05 ( 0.40 )	-0.04 ( 0.64 )
Change from Baseline at Week 48 (n=17, 46)	0.00 ( 0.94 )	-0.13 ( 0.78 )
Change from Baseline at Week 72 (n=13, 43)	-0.08 ( 1.04 )	-0.12 ( 0.63 )
Change from Baseline at Week 96 (n=8, 31)	-0.38 ( 0.74 )	-0.42 ( 0.99 )
Change from Baseline at Week 120 (n=3, 16)	-1.00 ( 0.00 )	-0.13 ( 0.81 )
Change from Baseline at Week 144 (n=2, 11)	-1.00 ( 1.41 )	-0.09 ( 0.54 )
Change from Baseline at Week 168 (n=0, 10)	6666 ( 6666 )	0.00 ( 0.67 )
Change from Baseline at Week 192 (n=1, 2)	-1.00 ( 9999 )	-0.50 ( 2.12 )
Change from Baseline at Week 216 (n=1, 0)	-1.00 ( 9999 )	6666 ( 6666 )

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

Top of page

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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 120

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	7	8
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=7, 8)	19.43 ( 12.19 )	11.32 ( 7.20 )
Change from Baseline at Week 24 (n=6, 4)	0.00 ( 6.20 )	1.50 ( 9.68 )
Change from Baseline at Week 48 (n=6, 2)	-2.83 ( 6.11 )	-3.00 ( 9.90 )
Change from Baseline at Week 72 (n=3, 1)	-5.00 ( 3.00 )	-13.00 ( 9999 )
Change from Baseline at Week 96 (n=2, 0)	-1.00 ( 7.07 )	6666 ( 6666 )
Change from Baseline at Week 120 (n=1, 0)	4.00 ( 9999 )	6666 ( 6666 )

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

Top of page

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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=32, 63)	3.66 ( 1.61 )	3.92 ( 1.50 )
Change from Baseline at Week 24 (n=20, 53)	-0.03 ( 0.38 )	-0.24 ( 0.71 )
Change from Baseline at Week 48 (n=18, 46)	-0.06 ( 0.42 )	-0.32 ( 0.65 )
Change from Baseline at Week 72 (n=12, 42)	0.21 ( 0.58 )	-0.29 ( 0.76 )
Change from Baseline at Week 96 (n=8, 29)	-0.50 ( 0.76 )	-0.03 ( 0.48 )
Change from Baseline at Week 120 (n=3, 16)	-0.50 ( 0.87 )	-0.22 ( 0.91 )
Change from Baseline at Week 144 (n=2, 11)	-1.00 ( 0.71 )	0.18 ( 0.68 )
Change from Baseline at Week 168 (n=1, 10)	-0.50 ( 9999 )	-0.15 ( 1.13 )
Change from Baseline at Week 192 (n=1, 2)	0.00 ( 9999 )	0.25 ( 1.06 )
Change from Baseline at Week 216 (n=1, 0)	-0.50 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

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

Top of page

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. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: score on scale
arithmetic mean (standard deviation)
Baseline: OD (n=32, 63)	0.560 ( 0.903 )	0.449 ( 0.712 )
Baseline: OS (n=32, 63)	0.456 ( 0.811 )	0.545 ( 0.836 )
Change from Baseline at Week 24: OD (n=20, 53)	-0.058 ( 0.512 )	0.039 ( 0.434 )
Change from Baseline at Week 24: OS (n=20, 53)	0.046 ( 0.242 )	-0.001 ( 0.500 )
Change from Baseline at Week 48: OD (n=18, 46)	-0.027 ( 0.097 )	0.053 ( 0.434 )
Change from Baseline at Week 48: OS (n=18, 46)	0.050 ( 0.252 )	-0.006 ( 0.591 )
Change from Baseline at Week 72: OD (n=12, 42)	-0.050 ( 0.140 )	-0.056 ( 0.260 )
Change from Baseline at Week 72: OS (n=12, 42)	-0.083 ( 0.595 )	-0.101 ( 0.492 )
Change from Baseline at Week 96: OD (n=8, 29)	-0.045 ( 0.099 )	-0.081 ( 0.580 )
Change from Baseline at Week 96: OS (n=8, 29)	-0.260 ( 0.707 )	-0.121 ( 0.571 )
Change from Baseline at Week 120: OD (n=3, 16)	-0.027 ( 0.142 )	-0.039 ( 0.637 )
Change from Baseline at Week 120: OS (n=3, 15)	0.000 ( 0.000 )	-0.229 ( 0.754 )
Change from Baseline at Week 144: OD (n=2, 11)	0.010 ( 0.127 )	0.149 ( 0.618 )
Change from Baseline at Week 144: OS (n=2, 11)	0.000 ( 0.000 )	-0.280 ( 0.846 )
Change from Baseline at Week 168: OD (n=1, 10)	-0.080 ( 9999 )	0.134 ( 0.663 )
Change from Baseline at Week 168: OS (n=1, 10)	-0.100 ( 9999 )	-0.320 ( 0.910 )
Change from Baseline at Week 192: OD (n=1, 2)	-0.180 ( 9999 )	-0.110 ( 0.156 )
Change from Baseline at Week 192: OS (n=1, 2)	0.080 ( 9999 )	-0.050 ( 0.071 )
Change from Baseline at Week 216: OD (n=1, 0)	-0.180 ( 9999 )	6666 ( 6666 )
Change from Baseline at Week 216: OS (n=1, 0)	-0.100 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

Secondary: Change from Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period

Top of page

End point title

Change from Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period

End point description

The LCSLC evaluates the visual function and captures the minimum size at which individuals can perceive letters of a particular contrast level. The change in binocular visual acuity, as assessed by the number of letters read correctly from a distance of 2 meters on 100%, 2.5% and 1.25% contrast level Sloan letter charts, was analyzed. The LCSLC is scored on a scale of 0-60. Higher scores indicate better visual function. A positive change from baseline indicates an improvement. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	29	60
Units: score on scale
arithmetic mean (standard deviation)
Baseline: 100% CHART (n=29, 60)	44.3 ( 16.1 )	44.4 ( 16.3 )
Baseline: 2.5% CHART (n=29, 60)	24.6 ( 16.2 )	22.6 ( 15.6 )
Baseline: 1.25% CHART (n=29, 60)	17.5 ( 15.7 )	14.9 ( 14.8 )
Change at Week 24: 100% CHART (n=19, 49)	0.5 ( 7.1 )	2.0 ( 5.3 )
Change at Week 24: 2.5% CHART (n=19, 49)	-2.8 ( 9.1 )	1.7 ( 7.1 )
Change at Week 24: 1.25% CHART (n=19, 49)	-4.2 ( 11.9 )	0.1 ( 7.5 )
Change at Week 48: 100% CHART (n=16, 43)	-3.4 ( 8.7 )	1.3 ( 6.1 )
Change at Week 48: 2.5% CHART (n=15, 43)	1.5 ( 6.1 )	4.0 ( 9.2 )
Change at Week 48: 1.25% CHART (n=15, 43)	1.7 ( 11.3 )	4.1 ( 9.3 )
Change at Week 72: 100% CHART (n=11, 41)	0.3 ( 5.9 )	2.8 ( 7.3 )
Change at Week 72: 2.5% CHART (n=11, 41)	-0.6 ( 8.6 )	2.6 ( 7.5 )
Change at Week 72: 1.25% CHART (n=11, 41)	-2.4 ( 8.3 )	0.4 ( 10.6 )
Change at Week 96: 100% CHART (n=7, 28)	3.3 ( 13.2 )	2.1 ( 12.4 )
Change at Week 96: 2.5% CHART (n=7, 28)	2.6 ( 20.1 )	2.3 ( 10.8 )
Change at Week 96: 1.25% CHART (n=7, 28)	-3.4 ( 11.3 )	-0.5 ( 11.3 )
Change at Week 120: 100% CHART (n=3, 14)	-1.0 ( 1.0 )	1.5 ( 10.6 )
Change at Week 120: 2.5% CHART (n=3, 14)	3.7 ( 4.6 )	2.1 ( 7.3 )
Change at Week 120: 1.25% CHART (n=3, 14)	-2.0 ( 5.0 )	1.6 ( 9.1 )
Change at Week 144: 100% CHART (n=2, 10)	-3.5 ( 2.1 )	0.4 ( 7.7 )
Change at Week 144: 2.5% CHART (n=2, 10)	17.5 ( 17.7 )	1.6 ( 12.0 )
Change at Week 144: 1.25% CHART (n=2, 10)	-7.0 ( 7.1 )	1.4 ( 12.2 )
Change at Week 168: 100% CHART (n=0, 10)	6666 ( 6666 )	2.1 ( 6.7 )
Change at Week 168: 2.5% CHART (n=0, 10)	6666 ( 6666 )	6.2 ( 8.2 )
Change at Week 168: 1.25% CHART (n=0, 10)	6666 ( 6666 )	0.3 ( 12.2 )
Change at Week 192: 100% CHART (n=1, 2)	1.0 ( 9999 )	-2.5 ( 3.5 )
Change at Week 192: 2.5% CHART (n=1, 2)	-1.0 ( 9999 )	-1.0 ( 4.2 )
Change at Week 192: 1.25% CHART (n=1, 2)	-8.0 ( 9999 )	-4.0 ( 7.1 )
Change at Week 216: 100% CHART (n=1, 0)	0.0 ( 9999 )	6666 ( 6666 )
Change at Week 216: 2.5% CHART (n=1, 0)	-1.0 ( 9999 )	6666 ( 6666 )
Change at Week 216: 1.25% CHART (n=1, 0)	-8.0 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

Secondary: Number of Participants with at Least One Adverse Event in the Double-Blind Period

Top of page

End point title

Number of Participants with at Least One Adverse Event in the Double-Blind 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. The Safety Analysis Population (SAF) included all randomized participants who had received at least 1 dose of satralizumab or placebo.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: participants	24	58

No statistical analyses for this end point

Secondary: Number of Participants with at Least One Serious Adverse Event in the Double-Blind Period

Top of page

End point title

Number of Participants with at Least One Serious Adverse Event in the Double-Blind 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. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: participants	5	12

No statistical analyses for this end point

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

Top of page

End point title

Number of Participants with Non-Serious Adverse Events of Special Interest in the Double-Blind 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. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: participants	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Selected Adverse Events in the Double-Blind Period

Top of page

End point title

Number of Participants with Selected Adverse Events in the Double-Blind Period

End point description

Selected adverse events for this study included: 1) all infections, 2) serious infections, 3) potential opportunistic infections, 4) 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), 5) psychiatric disorders and 6) anaphylaxis (an acute allergic/hypersensitivity reaction). The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo.

End point type

Secondary

End point timeframe

Up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: participants
All Infections	14	34
Serious Infections	3	6
Potential Opportunistic Infections	5	3
Injection-related Reactions	5	8
Psychiatric Disorders	4	13
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 Double-Blind Period

Top of page

End point title

Number of Participants With Suicidal Behaviors and Ideations Collected by Columbia-Suicide Severity Rating Scale in the Double-Blind 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. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo.

End point type

Secondary

End point timeframe

Baseline and Post-Baseline (up to Week 216)

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: participants
Baseline	0	9
Post-Baseline	1	3

No statistical analyses for this end point

Secondary: Serum Satralizumab Concentration During the DB Period

Top of page

End point title

Serum Satralizumab Concentration During the DB Period ^[3]

End point description

The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. Participants from SAF who received satralizumab were evaluated for this endpoint. 9999=SD was not calculable for 1 participant.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter up to Week 204

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during the DB period. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. Participants from SAF who received satralizumab were evaluated for this endpoint. Data was summarized together for this endpoint.

End point values	Satralizumab, then Satralizumab
Number of subjects analysed	62
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (n= 62)	145.13 ( 274.87 )
Week 2 (n= 61)	8099.70 ( 4541.66 )
Week 4 (n= 56)	14602.50 ( 8931.85 )
Week 5 (n= 44)	22564.32 ( 12306.09 )
Week 6 (n= 42)	20991.43 ( 12515.82 )
Week 8 (n= 60)	14864.35 ( 9955.41 )
Week 12 (n= 55)	14760.33 ( 10695.11 )
Week 16 (n= 53)	14613.11 ( 11276.95 )
Week 20 (n= 55)	14136.62 ( 12489.83 )
Week 24 (n= 55)	15634.18 ( 13310.22 )
Week 28 (n= 53)	15538.38 ( 13406.73 )
Week 32 (n= 52)	15111.94 ( 13827.06 )
Week 36 (n= 50)	16068.58 ( 14643.61 )
Week 40 (n= 46)	15428.04 ( 16059.35 )
Week 44 (n= 46)	16110.00 ( 15363.29 )
Week 48 (n= 44)	16701.16 ( 16790.77 )
Week 52 (n= 44)	15300.57 ( 14701.05 )
Week 56 (n= 45)	16390.82 ( 16130.69 )
Week 60 (n= 43)	16050.81 ( 14779.35 )
Week 64 (n= 42)	14385.10 ( 14084.24 )
Week 68 (n= 41)	14010.46 ( 13614.03 )
Week 72 (n= 42)	12895.69 ( 13849.12 )
Week 76 (n= 42)	14139.31 ( 14549.71 )
Week 80 (n= 42)	12709.79 ( 14098.26 )
Week 84 (n= 40)	11725.05 ( 13654.04 )
Week 88 (n= 35)	13733.17 ( 13438.07 )
Week 92 (n= 32)	12928.13 ( 13302.53 )
Week 96 (n= 31)	14036.58 ( 12644.16 )
Week 100 (n= 20)	14186.50 ( 12888.23 )
Week 104 (n= 22)	16647.00 ( 15568.61 )
Week 108 (n= 22)	15970.00 ( 13525.53 )
Week 112 (n= 19)	18657.37 ( 17426.82 )
Week 116 (n= 15)	17677.33 ( 16892.59 )
Week 120 (n= 14)	16615.00 ( 16751.13 )
Week 124 (n= 15)	13734.00 ( 12687.75 )
Week 128 (n= 15)	13738.00 ( 16005.33 )
Week 132 (n= 15)	13311.73 ( 15401.04 )
Week 136 (n= 13)	14208.54 ( 15266.48 )
Week 140 (n= 13)	13404.62 ( 12392.48 )
Week 144 (n= 11)	16138.18 ( 13782.26 )
Week 148 (n= 12)	14044.33 ( 12082.37 )
Week 152 (n= 12)	14644.42 ( 13123.67 )
Week 156 (n= 11)	18856.36 ( 20378.31 )
Week 160 (n= 11)	15238.18 ( 11360.62 )
Week 164 (n= 11)	14760.00 ( 11479.99 )
Week 168 (n= 10)	14199.60 ( 9911.22 )
Week 172 (n= 7)	17971.43 ( 16962.78 )
Week 176 (n= 7)	17922.86 ( 12815.57 )
Week 180 (n= 7)	15981.43 ( 9640.78 )
Week 184 (n= 6)	17911.67 ( 15142.19 )
Week 188 (n= 4)	16442.50 ( 13180.44 )
Week 192 (n= 2)	28750.00 ( 22415.28 )
Week 196 (n= 2)	26850.00 ( 20152.54 )
Week 200 (n= 1)	45000.00 ( 9999 )
Week 204 (n= 1)	34500.00 ( 9999 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	30	62
Units: pg/mL
arithmetic mean (standard deviation)
Baseline (n=29, 62)	3.66 ( 6.49 )	3.49 ( 5.14 )
Week 2 (n=30, 60)	5.90 ( 16.31 )	30.14 ( 26.07 )
Week 4 (n=28, 61)	5.41 ( 10.02 )	51.53 ( 126.49 )
Week 8 (n=26, 61)	3.30 ( 4.59 )	30.88 ( 25.57 )
Week 12 (n=25, 53)	3.40 ( 4.21 )	32.02 ( 24.91 )
Week 16 (n=23, 53)	3.72 ( 4.54 )	28.59 ( 23.27 )
Week 20 (n=22, 55)	2.99 ( 2.88 )	24.06 ( 19.59 )
Week 24 (n=20, 55)	3.68 ( 4.02 )	26.27 ( 23.19 )
Week 28 (n=20, 53)	3.88 ( 4.24 )	26.89 ( 24.01 )
Week 32 (n=22, 52)	3.43 ( 3.20 )	33.29 ( 37.93 )
Week 36 (n=20, 50)	3.78 ( 3.65 )	26.03 ( 21.75 )
Week 40 (n=19, 46)	4.82 ( 6.45 )	24.16 ( 19.93 )
Week 44 (n=18, 46)	3.47 ( 3.65 )	26.16 ( 20.39 )
Week 48 (n=17, 43)	4.58 ( 4.21 )	29.61 ( 27.37 )
Week 52 (n=18, 44)	3.52 ( 3.36 )	26.94 ( 22.26 )
Week 56 (n=15, 45)	4.13 ( 5.26 )	33.15 ( 40.66 )
Week 60 (n=12, 43)	3.28 ( 3.65 )	31.34 ( 25.38 )
Week 64 (n=14, 41)	4.08 ( 4.48 )	30.60 ( 24.55 )
Week 68 (n=14, 41)	2.75 ( 3.35 )	30.56 ( 44.67 )
Week 72 (n=12, 41)	2.95 ( 4.80 )	23.16 ( 17.54 )
Week 76 (n=12, 42)	2.44 ( 3.04 )	24.08 ( 16.78 )
Week 80 (n=11, 41)	1.57 ( 0.00 )	24.86 ( 17.89 )
Week 84 (n=12, 40)	2.27 ( 1.84 )	27.61 ( 23.04 )
Week 88 (n=9, 35)	1.57 ( 0.00 )	26.51 ( 20.07 )
Week 92 (n=10, 31)	3.38 ( 4.80 )	25.48 ( 17.24 )
Week 96 (n=7, 31)	1.57 ( 0.00 )	24.57 ( 15.25 )
Week 100 (n=5, 18)	1.57 ( 0.00 )	26.31 ( 18.74 )
Week 104 (n=7, 22)	1.57 ( 0.00 )	26.30 ( 19.96 )
Week 108 (n=6, 21)	1.57 ( 0.00 )	27.64 ( 23.97 )
Week 112 (n=3, 19)	1.57 ( 0.00 )	27.39 ( 22.72 )
Week 116 (n=4, 15)	1.57 ( 0.00 )	31.73 ( 23.27 )
Week 120 (n=3, 13)	1.57 ( 0.00 )	55.92 ( 68.46 )
Week 124 (n=3, 15)	1.57 ( 0.00 )	29.46 ( 19.49 )
Week 128 (n=2, 14)	1.57 ( 0.00 )	31.20 ( 21.29 )
Week 132 (n=2, 15)	1.57 ( 0.00 )	33.84 ( 34.36 )
Week 136 (n=2, 13)	1.57 ( 0.00 )	51.83 ( 73.68 )
Week 140 (n=1, 12)	1.57 ( 9999 )	41.00 ( 45.44 )
Week 144 (n=2, 11)	1.57 ( 0.00 )	28.26 ( 25.64 )
Week 148 (n=2, 12)	1.57 ( 0.00 )	28.76 ( 21.52 )
Week 152 (n=1, 12)	1.57 ( 9999 )	28.07 ( 23.66 )
Week 156 (n=1, 11)	1.57 ( 9999 )	27.25 ( 19.19 )
Week 160 (n=1, 11)	1.57 ( 9999 )	29.60 ( 20.30 )
Week 164 (n=1, 11)	1.57 ( 9999 )	34.00 ( 24.13 )
Week 168 (n=1, 10)	1.57 ( 9999 )	26.29 ( 20.85 )
Week 172 (n=1, 7)	1.57 ( 9999 )	23.57 ( 6.59 )
Week 176 (n=1, 7)	1.57 ( 9999 )	27.73 ( 11.10 )
Week 180 (n=1, 7)	1.57 ( 9999 )	24.09 ( 9.21 )
Week 184 (n=1, 6)	3.63 ( 9999 )	17.34 ( 8.47 )
Week 188 (n=1, 4)	5.21 ( 9999 )	17.78 ( 7.22 )
Week 192 (n=1, 2)	1.57 ( 9999 )	16.55 ( 3.89 )
Week 196 (n=1, 2)	1.57 ( 9999 )	14.45 ( 2.76 )
Week 200 (n=1, 1)	1.57 ( 9999 )	36.90 ( 9999 )
Week 204 (n=1, 1)	1.57 ( 9999 )	12.30 ( 9999 )
Week 208 (n=1, 0)	1.57 ( 9999 )	6666 ( 6666 )
Week 212 (n=1, 0)	1.57 ( 9999 )	6666 ( 6666 )
Week 216 (n=1, 0)	1.57 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	62
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (n=32, 62)	31.88 ( 7.50 )	33.18 ( 7.72 )
Week 2 (n=30, 61)	32.72 ( 8.09 )	396.49 ( 80.09 )
Week 4 (n=29, 61)	44.79 ( 64.73 )	509.21 ( 121.99 )
Week 8 (n=27, 61)	33.23 ( 7.21 )	560.63 ( 164.11 )
Week 12 (n=26, 55)	33.02 ( 7.65 )	582.36 ( 169.71 )
Week 16 (n=24, 53)	31.60 ( 8.18 )	582.22 ( 204.20 )
Week 20 (n=22, 55)	32.99 ( 8.14 )	555.64 ( 210.76 )
Week 24 (n=20, 55)	32.47 ( 8.69 )	573.01 ( 217.93 )
Week 28 (n=20, 53)	31.83 ( 9.71 )	565.29 ( 219.88 )
Week 32 (n=22, 52)	33.33 ( 9.97 )	564.13 ( 215.59 )
Week 36 (n=20, 50)	34.03 ( 7.79 )	572.31 ( 207.35 )
Week 40 (n=19, 46)	33.64 ( 9.44 )	554.90 ( 241.34 )
Week 44 (n=18, 46)	33.97 ( 9.05 )	585.62 ( 219.45 )
Week 48 (n=17, 44)	33.72 ( 8.18 )	591.06 ( 213.04 )
Week 52 (n=18, 44)	33.47 ( 7.58 )	575.56 ( 210.84 )
Week 56 (n=15, 45)	30.34 ( 5.21 )	585.40 ( 233.38 )
Week 60 (n=13, 43)	30.58 ( 6.81 )	586.40 ( 226.21 )
Week 64 (n=14, 42)	32.27 ( 7.63 )	602.72 ( 239.25 )
Week 68 (n=14, 41)	31.19 ( 7.23 )	617.80 ( 244.63 )
Week 72 (n=13, 42)	31.12 ( 7.76 )	543.95 ( 224.00 )
Week 76 (n=12, 42)	30.56 ( 7.06 )	558.67 ( 234.41 )
Week 80 (n=11, 41)	33.36 ( 9.91 )	558.73 ( 235.60 )
Week 84 (n=12, 40)	30.95 ( 8.96 )	552.37 ( 226.76 )
Week 88 (n=10, 35)	32.05 ( 7.23 )	547.93 ( 211.74 )
Week 92 (n=10, 32)	28.93 ( 5.72 )	580.64 ( 201.78 )
Week 96 (n=,8 31)	32.88 ( 5.62 )	561.64 ( 205.00 )
Week 100 (n=7, 19)	31.84 ( 7.62 )	559.18 ( 194.43 )
Week 104 (n=7, 22)	31.70 ( 8.81 )	598.05 ( 192.99 )
Week 108 (n=6, 21)	30.55 ( 6.94 )	592.06 ( 193.20 )
Week 112 (n=4, 19)	29.93 ( 8.47 )	603.31 ( 227.68 )
Week 116 (n=4, 15)	34.30 ( 13.37 )	609.37 ( 198.61 )
Week 120 (n=3, 13)	38.20 ( 10.96 )	625.15 ( 229.67 )
Week 124 (n=3, 15)	37.87 ( 13.59 )	580.07 ( 240.15 )
Week 128 (n=2, 15)	44.50 ( 2.40 )	574.54 ( 214.94 )
Week 132 (n=2, 15)	29.80 ( 8.63 )	575.40 ( 213.45 )
Week 136 (n=2, 13)	29.45 ( 11.53 )	593.92 ( 209.84 )
Week 140 (n=1, 13)	37.20 ( 9999 )	627.32 ( 232.08 )
Week 144 (n=2, 11)	31.10 ( 10.18 )	693.82 ( 239.70 )
Week 148 (n=2, 12)	28.55 ( 13.08 )	690.83 ( 142.94 )
Week 152 (n=1, 12)	33.60 ( 9999 )	626.41 ( 229.59 )
Week 156 (n=1, 11)	39.90 ( 9999 )	682.82 ( 156.88 )
Week 160 (n=1, 11)	45.00 ( 9999 )	694.18 ( 127.92 )
Week 164 (n=1, 11)	43.00 ( 9999 )	696.18 ( 106.76 )
Week 168 (n=1, 10)	40.60 ( 9999 )	681.00 ( 122.60 )
Week 172 (n=1, 7)	49.70 ( 9999 )	672.71 ( 107.83 )
Week 176 (n=1, 7)	45.50 ( 9999 )	700.71 ( 90.64 )
Week 180 (n=1, 7)	55.60 ( 9999 )	702.00 ( 75.60 )
Week 184 (n=1, 6)	41.60 ( 9999 )	678.33 ( 78.20 )
Week 188 (n=1, 4)	40.00 ( 9999 )	688.75 ( 143.82 )
Week 192 (n=1, 2)	43.40 ( 9999 )	668.00 ( 192.33 )
Week 196 (n=1, 2)	38.00 ( 9999 )	630.00 ( 141.42 )
Week 200 (n=1, 1)	35.80 ( 9999 )	815.00 ( 9999 )
Week 204 (n=1, 1)	33.70 ( 9999 )	783.00 ( 9999 )
Week 208 (n=1, 0)	35.60 ( 9999 )	6666 ( 6666 )
Week 212 (n=1, 0)	30.50 ( 9999 )	6666 ( 6666 )
Week 216 (n=1, 0)	37.60 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. 9999=SD was not calculable for 1 participant. 6666=0 participants.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, and every 4 weeks thereafter up to Week 216

End point values	Placebo, then Satralizumab	Satralizumab, then Satralizumab
Number of subjects analysed	32	63
Units: mg/L
arithmetic mean (standard deviation)
Baseline (n=32, 63)	3.08 ( 3.77 )	4.95 ( 8.67 )
Week 2 (n=30, 62)	3.51 ( 4.55 )	0.93 ( 2.35 )
Week 4 (n=29, 60)	3.45 ( 6.24 )	0.82 ( 1.64 )
Week 8 (n=27, 61)	4.56 ( 8.97 )	0.83 ( 1.99 )
Week 12 (n=26, 55)	4.23 ( 7.23 )	1.23 ( 3.19 )
Week 16 (n=24, 53)	5.30 ( 9.17 )	1.56 ( 4.53 )
Week 20 (n=22, 55)	4.07 ( 5.20 )	1.78 ( 3.72 )
Week 24 (n=19, 55)	3.53 ( 4.08 )	1.72 ( 4.05 )
Week 28 (n=20, 53)	5.85 ( 9.99 )	2.35 ( 5.61 )
Week 32 (n=22, 52)	3.97 ( 5.20 )	2.06 ( 4.28 )
Week 36 (n=20, 50)	3.77 ( 4.40 )	1.56 ( 3.36 )
Week 40 (n=18, 45)	6.77 ( 10.92 )	2.55 ( 5.53 )
Week 44 (n=18, 46)	5.44 ( 8.72 )	3.31 ( 11.31 )
Week 48 (n=17, 44)	4.70 ( 5.43 )	1.79 ( 3.24 )
Week 52 (n=18, 42)	3.82 ( 4.75 )	1.90 ( 3.69 )
Week 56 (n=15, 45)	5.33 ( 8.87 )	2.32 ( 5.44 )
Week 60 (n=13, 43)	4.54 ( 5.60 )	3.20 ( 11.86 )
Week 64 (n=14, 43)	3.76 ( 4.62 )	1.92 ( 3.55 )
Week 68 (n=14, 42)	3.30 ( 5.11 )	3.65 ( 8.52 )
Week 72 (n=13, 42)	5.07 ( 11.87 )	3.33 ( 7.30 )
Week 76 (n=12, 42)	1.98 ( 2.12 )	2.79 ( 6.54 )
Week 80 (n=11, 41)	1.10 ( 0.72 )	2.83 ( 7.09 )
Week 84 (n=12, 40)	2.31 ( 4.66 )	3.81 ( 10.18 )
Week 88 (n=10, 35)	1.94 ( 3.38 )	2.64 ( 6.56 )
Week 92 (n=10, 32)	4.49 ( 10.18 )	1.94 ( 4.11 )
Week 96 (n=8, 31)	1.76 ( 2.47 )	1.64 ( 3.37 )
Week 100 (n=7, 20)	0.90 ( 0.87 )	1.87 ( 4.28 )
Week 104 (n=7, 22)	1.13 ( 1.01 )	1.93 ( 4.43 )
Week 108 (n=6, 21)	2.20 ( 3.16 )	2.56 ( 7.40 )
Week 112 (n=4, 19)	2.25 ( 2.68 )	1.53 ( 2.86 )
Week 116 (n=4, 15)	2.28 ( 3.41 )	1.19 ( 1.93 )
Week 120 (n=2, 14)	1.55 ( 1.63 )	6.05 ( 14.33 )
Week 124 (n=3, 15)	1.50 ( 1.04 )	3.24 ( 8.32 )
Week 128 (n=2, 15)	0.65 ( 0.64 )	3.09 ( 7.52 )
Week 132 (n=2, 15)	2.55 ( 1.77 )	2.66 ( 5.04 )
Week 136 (n=2, 15)	2.70 ( 1.27 )	2.85 ( 7.29 )
Week 140 (n=1, 13)	2.50 ( 9999 )	4.54 ( 9.57 )
Week 144 (n=2, 11)	2.65 ( 2.19 )	0.96 ( 1.75 )
Week 148 (n=2, 12)	4.80 ( 0.99 )	0.87 ( 1.44 )
Week 152 (n=1, 12)	1.20 ( 9999 )	0.79 ( 0.79 )
Week 156 (n=1, 11)	1.80 ( 9999 )	0.71 ( 1.17 )
Week 160 (n=1, 11)	1.20 ( 9999 )	0.82 ( 1.36 )
Week 164 (n=1, 11)	1.30 ( 9999 )	0.54 ( 0.50 )
Week 168 (n=1, 10)	1.30 ( 9999 )	0.37 ( 0.22 )
Week 172 (n=1, 7)	1.30 ( 9999 )	0.19 ( 0.09 )
Week 176 (n=1, 7)	1.30 ( 9999 )	0.25 ( 0.17 )
Week 180 (n=1, 7)	1.20 ( 9999 )	0.27 ( 0.16 )
Week 184 (n=1, 6)	1.10 ( 9999 )	0.22 ( 0.11 )
Week 188 (n=1, 4)	2.40 ( 9999 )	0.21 ( 0.13 )
Week 192 (n=1, 2)	1.10 ( 9999 )	0.33 ( 0.25 )
Week 196 (n=1, 2)	2.00 ( 9999 )	0.15 ( 0.00 )
Week 200 (n=1, 1)	1.10 ( 9999 )	0.50 ( 9999 )
Week 204 (n=0, 1)	6666 ( 6666 )	0.15 ( 9999 )
Week 208 (n=1, 0)	1.00 ( 9999 )	6666 ( 6666 )
Week 212 (n=1, 0)	1.60 ( 9999 )	6666 ( 6666 )
Week 216 (n=1, 0)	1.10 ( 9999 )	6666 ( 6666 )

No statistical analyses for this end point

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

Top of page

End point title

Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period ^[4]

End point description

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

End point type

Secondary

End point timeframe

Up to Week 216

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Reported here is the percentage of participants with at least one positive anti-drug antibody measurement during the DB period. The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo. Participants from SAF who received satralizumab were evaluated for this endpoint. Data was summarized together for this endpoint.

End point values	Satralizumab, then Satralizumab
Number of subjects analysed	63
Units: percentage of participants
number (not applicable)	71.4

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Double Blind Period: Up to primary clinical cut-off date, 12 Oct 2018 (up to approximately 217 weeks) Open Label Period: Up to primary clinical cut-off date, 31-Jan-2022 (up to approximately 336 weeks)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo Double Blind Period

Reporting group description

Participants received matching placebo, subcutaneous (SC) injection at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period. Participants who experienced a protocol defined relapse could continue in the Open Label Extension (OLE) period 31 days after relapse. Participants who completed the DB period without relapse could participate in the OLE period 4 weeks after receiving their last dose in the DB period.

Reporting group title

SA237 Double Blind Period

Reporting group description

Reporting group title

Placebo Open Label Period

Reporting group description

Participants received matching placebo, subcutaneous (SC) injection at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period. Following the DB period, all participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD).

Reporting group title

SA237 Open Label Period

Reporting group description

Participants received satralizumab 120 mg subcutaneous (SC) injection at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period. Following the DB period, all participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD).

Serious adverse events	Placebo Double Blind Period	SA237 Double Blind Period	Placebo Open Label Period	SA237 Open Label Period
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 32 (15.63%)	12 / 63 (19.05%)	3 / 28 (10.71%)	7 / 56 (12.50%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian germ cell teratoma benign
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Post procedural haematoma
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fractured sacrum
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cervical radiculopathy
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intracranial aneurysm
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neuromyelitis optica pseudo relapse
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Hypothermia
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Visual impairment
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Enterocolitis
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Apnoea
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	0 / 32 (0.00%)	2 / 63 (3.17%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cystitis
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 32 (0.00%)	2 / 63 (3.17%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo Double Blind Period	SA237 Double Blind Period	Placebo Open Label Period	SA237 Open Label Period
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 32 (71.88%)	57 / 63 (90.48%)	23 / 28 (82.14%)	42 / 56 (75.00%)
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 32 (6.25%)	7 / 63 (11.11%)	1 / 28 (3.57%)	2 / 56 (3.57%)
occurrences all number	3	9	1	2
Influenza like illness
subjects affected / exposed	1 / 32 (3.13%)	2 / 63 (3.17%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	3	5	1	13
Injection site erythema
subjects affected / exposed	2 / 32 (6.25%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	3	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 32 (0.00%)	3 / 63 (4.76%)	2 / 28 (7.14%)	2 / 56 (3.57%)
occurrences all number	0	3	2	2
Pain
subjects affected / exposed	1 / 32 (3.13%)	2 / 63 (3.17%)	0 / 28 (0.00%)	3 / 56 (5.36%)
occurrences all number	1	2	0	3
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	3 / 28 (10.71%)	1 / 56 (1.79%)
occurrences all number	0	1	3	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 32 (3.13%)	2 / 63 (3.17%)	3 / 28 (10.71%)	3 / 56 (5.36%)
occurrences all number	1	3	3	3
Oropharyngeal pain
subjects affected / exposed	3 / 32 (9.38%)	3 / 63 (4.76%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	3	3	1	4
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 32 (6.25%)	2 / 63 (3.17%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences all number	2	2	0	2
Depression
subjects affected / exposed	0 / 32 (0.00%)	6 / 63 (9.52%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences all number	0	10	1	0
Insomnia
subjects affected / exposed	1 / 32 (3.13%)	6 / 63 (9.52%)	3 / 28 (10.71%)	2 / 56 (3.57%)
occurrences all number	1	6	4	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 32 (0.00%)	4 / 63 (6.35%)	1 / 28 (3.57%)	1 / 56 (1.79%)
occurrences all number	0	4	2	1
Blood cholesterol increased
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	3 / 28 (10.71%)	4 / 56 (7.14%)
occurrences all number	0	2	5	9
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 32 (3.13%)	4 / 63 (6.35%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences all number	1	5	0	2
Lymphocyte count decreased
subjects affected / exposed	1 / 32 (3.13%)	2 / 63 (3.17%)	2 / 28 (7.14%)	2 / 56 (3.57%)
occurrences all number	1	4	6	2
Neutrophil count decreased
subjects affected / exposed	2 / 32 (6.25%)	1 / 63 (1.59%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences all number	2	1	6	0
White blood cell count decreased
subjects affected / exposed	0 / 32 (0.00%)	5 / 63 (7.94%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	0	9	1	10
Blood fibrinogen decreased
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	3 / 28 (10.71%)	4 / 56 (7.14%)
occurrences all number	0	4	4	5
Blood potassium increased
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	2 / 28 (7.14%)	0 / 56 (0.00%)
occurrences all number	0	0	3	0
Complement factor decreased
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	1 / 28 (3.57%)	5 / 56 (8.93%)
occurrences all number	0	0	2	10
International normalised ratio increased
subjects affected / exposed	1 / 32 (3.13%)	0 / 63 (0.00%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	1	0	2	1
Low density lipoprotein increased
subjects affected / exposed	1 / 32 (3.13%)	1 / 63 (1.59%)	2 / 28 (7.14%)	2 / 56 (3.57%)
occurrences all number	1	1	6	3
Complement factor C4 decreased
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	0	0	3	1
Prothrombin time prolonged
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	0	0	2	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 32 (3.13%)	3 / 63 (4.76%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	1	3	2	1
Fall
subjects affected / exposed	2 / 32 (6.25%)	4 / 63 (6.35%)	0 / 28 (0.00%)	4 / 56 (7.14%)
occurrences all number	2	4	0	10
Skin abrasion
subjects affected / exposed	2 / 32 (6.25%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	2	1	0	0
Nervous system disorders
Balance disorder
subjects affected / exposed	2 / 32 (6.25%)	2 / 63 (3.17%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences all number	2	2	0	1
Dizziness
subjects affected / exposed	2 / 32 (6.25%)	3 / 63 (4.76%)	2 / 28 (7.14%)	5 / 56 (8.93%)
occurrences all number	3	3	3	6
Headache
subjects affected / exposed	4 / 32 (12.50%)	10 / 63 (15.87%)	4 / 28 (14.29%)	8 / 56 (14.29%)
occurrences all number	5	13	4	12
Hypoaesthesia
subjects affected / exposed	0 / 32 (0.00%)	5 / 63 (7.94%)	2 / 28 (7.14%)	4 / 56 (7.14%)
occurrences all number	0	6	2	5
Paraesthesia
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	3 / 56 (5.36%)
occurrences all number	0	1	0	14
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	1 / 32 (3.13%)	4 / 63 (6.35%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	10	5	3	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 32 (3.13%)	1 / 63 (1.59%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	1	1	1	3
Eye disorders
Vision blurred
subjects affected / exposed	2 / 32 (6.25%)	1 / 63 (1.59%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences all number	2	1	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 32 (6.25%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	3	1	0	0
Constipation
subjects affected / exposed	2 / 32 (6.25%)	3 / 63 (4.76%)	3 / 28 (10.71%)	6 / 56 (10.71%)
occurrences all number	2	3	3	6
Diarrhoea
subjects affected / exposed	0 / 32 (0.00%)	5 / 63 (7.94%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	0	19	1	5
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 32 (6.25%)	2 / 63 (3.17%)	0 / 28 (0.00%)	1 / 56 (1.79%)
occurrences all number	2	2	0	1
Nausea
subjects affected / exposed	2 / 32 (6.25%)	11 / 63 (17.46%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	6	15	1	4
Toothache
subjects affected / exposed	0 / 32 (0.00%)	2 / 63 (3.17%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	0	2	2	1
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 32 (0.00%)	7 / 63 (11.11%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences all number	0	9	2	0
Rash
subjects affected / exposed	1 / 32 (3.13%)	10 / 63 (15.87%)	3 / 28 (10.71%)	3 / 56 (5.36%)
occurrences all number	2	16	3	3
Dermatitis
subjects affected / exposed	0 / 32 (0.00%)	2 / 63 (3.17%)	2 / 28 (7.14%)	0 / 56 (0.00%)
occurrences all number	0	3	2	0
Dermatitis contact
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	2 / 28 (7.14%)	0 / 56 (0.00%)
occurrences all number	0	1	2	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	2 / 32 (6.25%)	1 / 63 (1.59%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	2	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 32 (9.38%)	14 / 63 (22.22%)	3 / 28 (10.71%)	6 / 56 (10.71%)
occurrences all number	3	14	3	6
Back pain
subjects affected / exposed	3 / 32 (9.38%)	4 / 63 (6.35%)	3 / 28 (10.71%)	4 / 56 (7.14%)
occurrences all number	3	5	3	7
Muscle spasms
subjects affected / exposed	0 / 32 (0.00%)	3 / 63 (4.76%)	0 / 28 (0.00%)	3 / 56 (5.36%)
occurrences all number	0	3	0	3
Musculoskeletal stiffness
subjects affected / exposed	0 / 32 (0.00%)	4 / 63 (6.35%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	0	4	0	0
Myalgia
subjects affected / exposed	0 / 32 (0.00%)	4 / 63 (6.35%)	1 / 28 (3.57%)	4 / 56 (7.14%)
occurrences all number	0	5	1	4
Pain in extremity
subjects affected / exposed	3 / 32 (9.38%)	9 / 63 (14.29%)	2 / 28 (7.14%)	7 / 56 (12.50%)
occurrences all number	3	12	2	11
Arthritis
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	0 / 28 (0.00%)	3 / 56 (5.36%)
occurrences all number	0	1	0	3
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 32 (6.25%)	2 / 63 (3.17%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences all number	2	2	0	3
Cellulitis
subjects affected / exposed	0 / 32 (0.00%)	4 / 63 (6.35%)	0 / 28 (0.00%)	2 / 56 (3.57%)
occurrences all number	0	5	0	4
Influenza
subjects affected / exposed	2 / 32 (6.25%)	3 / 63 (4.76%)	4 / 28 (14.29%)	1 / 56 (1.79%)
occurrences all number	3	3	4	1
Nasopharyngitis
subjects affected / exposed	1 / 32 (3.13%)	9 / 63 (14.29%)	5 / 28 (17.86%)	6 / 56 (10.71%)
occurrences all number	1	11	8	8
Oral candidiasis
subjects affected / exposed	2 / 32 (6.25%)	0 / 63 (0.00%)	1 / 28 (3.57%)	0 / 56 (0.00%)
occurrences all number	3	0	1	0
Tooth abscess
subjects affected / exposed	2 / 32 (6.25%)	0 / 63 (0.00%)	0 / 28 (0.00%)	0 / 56 (0.00%)
occurrences all number	2	0	0	0
Upper respiratory tract infection
subjects affected / exposed	6 / 32 (18.75%)	10 / 63 (15.87%)	8 / 28 (28.57%)	10 / 56 (17.86%)
occurrences all number	14	20	19	32
Urinary tract infection
subjects affected / exposed	8 / 32 (25.00%)	11 / 63 (17.46%)	5 / 28 (17.86%)	10 / 56 (17.86%)
occurrences all number	23	36	8	23
Cystitis
subjects affected / exposed	0 / 32 (0.00%)	3 / 63 (4.76%)	2 / 28 (7.14%)	0 / 56 (0.00%)
occurrences all number	0	3	2	0
Fungal infection
subjects affected / exposed	0 / 32 (0.00%)	1 / 63 (1.59%)	2 / 28 (7.14%)	1 / 56 (1.79%)
occurrences all number	0	1	2	1
Otitis media
subjects affected / exposed	0 / 32 (0.00%)	0 / 63 (0.00%)	2 / 28 (7.14%)	0 / 56 (0.00%)
occurrences all number	0	0	2	0
Sinusitis
subjects affected / exposed	0 / 32 (0.00%)	2 / 63 (3.17%)	1 / 28 (3.57%)	3 / 56 (5.36%)
occurrences all number	0	3	1	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

18 Feb 2014

V2: Study design: The randomization was stratified by prior therapy for prevention of NMO/NMOSD attack (B-cell depleting therapy or immunosuppressants/others) and the most recent attack in the last one year prior to screening (first attack or relapse). Exclusion criteria: History of drug or alcohol abuse within 1 year prior to baseline; History of acute diverticulitis that, in the Investigator’s opinion, may lead to increased risk of complications such as lower gastrointestinal perforation. Screening for possible relapse during the study: A Relapse Assessment Form, including the time and content of every report of a possible event was prepared. Patients were instructed to remember accurately the time and content of every symptom of a possible relapse and to contact the study site if they had such symptoms. During the double-blind period, the site contacted the patient weekly by phone calls between the scheduled site visits, to query for any change in symptoms or other signs of a potential relapse. Assessment for suicidality was added to the safety section (Columbia-Suicide Severity Rating Scale [C-SSRS]). The number of patients who are negative for anti-AQP4 antibody at screening were limited to approximately 30% of total study population.

26 May 2014

V3: Change in protocol-defined relapse: new or worsening neurologic symptoms had to meet any of the listed symptoms. Futility analysis was removed from the role of the independent data monitoring committee (IDMC). Hypersensitivity to gadolinium was removed from the exclusion criteria. Additional procedure was added for scripted questions at patient discontinuation to minimize dropout and not to miss potential relapse. Time limit for participants to report relapse event was set. Beginning time point of TFR was modified to start at randomization. Considering the clinical practice in the US, the permitted treatment for relapse was modified. For general safety patients who had a risk of Stevens-Johnson syndrome (SJS) were excluded from the study.

02 Sep 2014

V4: Protocol-defined relapse criteria were updated to specify the score increase required to qualify as clinically meaningful for the Expanded Disability Status Scale (EDSS) and Functional System Score (FSS) when the baseline score is zero. Instructions for tuberculosis screening and treatment were updated.

05 Nov 2015

V5: The right to enter the extension period was modified in that protocol-defined relapse had to be adjudicated by the Clinical Endpoint Committee (CEC) in the double-blind Period. The open-label extension period was extended until commercial availability of the drug. Statistical method for primary analysis was changed to a log-rank based permutation test. Clarification was provided to mention that participants who experienced a relapse during the extension period could continue administration of satralizumab at the discretion of the Investigator. Screening procedure for hepatitis C virus (HCV) was modified to mention that if a patient tested positive, but ribonucleic acid (RNA) was undetectable 12 weeks after HCV treatment completion, the patient could be enrolled. Assessments performed at the Withdrawal visit were provided separately for the double-blind period and extension period. Assessments after Week 48 of the extension period were included, because the open-label extension period was extended until commercial availability.

01 Mar 2016

V6: Recruitment was changed from North America only to include the rest of the world. Total number of participants in the study was increased to 90. The total number of relapse events was changed because the hazard ratio assumption of satralizumab over placebo was modified. The end of the double-blind period was then defined as the date of primary analysis when the total number of relapses reached 44. Procedure for triplicate ECG was clarified for participants who consented to additional pharmacokinetic (PK) sampling.

13 Jul 2017

V7: Satralizumab prefilled syringe (PFS) with needle safety device (NSD) was implemented in the study. The number of participants to collect blood sample for plasmablast was expanded to all participants. Clarification was included that Zarit Burden Interview (ZBI) was optional and would be performed in selected countries for caregivers who signed informed consent to caregiver burden assessment.

14 Jun 2018

V8: To prevent prolonged exposure to an unknown risk-benefit balance drug, the definition of the end of the double-blind period was changed to include a maximal duration completion of 1.5 years after the date of the last participant randomized, if the target number of protocol-defined relapses (PDRs) adjudicated by Clinical Endpoint Committee (CEC) had not been reached. The analysis method for primary endpoint was changed to a stratified two-sided log-rank test using strata of prior therapy for prevention of NMO/NMOSD attack (B-cell depleting therapy or immunosuppressants/others) and the most recent attack in the last one year prior to screening (first attack or relapse). Statistical methods were clarified for VAS in pain score and FACIT fatigue scale score to be ANCOVA with hot-deck imputation. It was clarified that non-linear mixed-effects modeling would be used to analyze the sparse sampling dose-concentration-time data of satralizumab.

Were there any global interruptions to the trial? No

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

None reported

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

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

Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica 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 (DB) Period

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

Secondary: Change in Visual Analogue Scale (VAS) for Pain from Baseline to Week 24

Secondary: Change in Visual Analogue Scale (VAS) for Pain from Baseline to Week 24

Secondary: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale from Baseline to Week 24

Secondary: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale from Baseline to Week 24

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 Short Form Generic Health Survey (SF-36) Bodily Pain Domain Scores at 24 Week Intervals During the DB Period

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

Secondary: Change from Baseline in 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 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: Change from Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Speed of Timed 25-Foot Walk (T25W) 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 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 Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period

Secondary: Change from Baseline in Visual Function (Low-Contrast Sloan Letter Chart [LCSLC]) Scores at 24 Week Intervals During the DB Period

Secondary: Number of Participants with at Least One Adverse Event in the Double-Blind Period

Secondary: Number of Participants with at Least One Adverse Event in the Double-Blind Period

Secondary: Number of Participants with at Least One Serious Adverse Event in the Double-Blind Period

Secondary: Number of Participants with at Least One Serious Adverse Event in the Double-Blind Period

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

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

Secondary: Number of Participants with Selected Adverse Events in the Double-Blind Period

Secondary: Number of Participants with Selected Adverse Events in the Double-Blind Period

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

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

Secondary: Serum Satralizumab Concentration During the DB Period

Secondary: Serum Satralizumab 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: 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: 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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)