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

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

Results information
Results version number	v1
This version publication date	27 Sep 2020
First version publication date	27 Sep 2020
Other versions	v2 , v3

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

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Trial information

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Sponsor protocol code

BN40898

ISRCTN number

US NCT number

NCT02028884

WHO universal trial number (UTN)

Sponsor organisation name

F. 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

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

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001625-PIP01-14

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

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

Analysis stage

Interim

Date of interim/final analysis

06 Jun 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Jun 2018

Global end of trial reached?

Main objective of the trial

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

Protection of trial subjects

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

Background therapy

All participants received corticosteroids as background therapy.

Evidence for comparator

Actual start date of recruitment

20 Feb 2014

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Japan: 22

Country: Number of subjects enrolled

Poland: 23

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

Ukraine: 3

Country: Number of subjects enrolled

United States: 2

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants took part in the double-blind period up to the clinical cut-off date (CCOD: 06 June 2018). The CCOD was defined by the onset date of the 26th clinical endpoint committee-confirmed protocol-defined relapse (PDR). The study is ongoing in the open label extension period.

Screening details

Participants with neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) were randomized 1:1 to receive either satralizumab 120 mg or matching placebo, in addition to baseline immunosuppressive treatments.

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 + Baseline Treatment, then Satralizumab

Arm description

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

Arm type

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 (Q4W).

Investigational medicinal product name

Baseline treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One of the following drugs at a stable dose was required as monotherapy for baseline treatment during the double-blind period: azathioprine (AZA); mycophenolate mofetil (MMF); or oral corticosteroids (CS). For participants aged 12 to 17 years at the time of informed consent, baseline treatment with AZA or MMF in combination with oral CS was also permitted. Change or termination of baseline treatment was only permitted during the open-label extension period.

Satralizumab + Baseline Treatment, then Satralizumab

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Baseline treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237, RG6168, RO5333787

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

Number of subjects in period 1	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Started	42	41
Completed	24	18
Not completed	18	23
Consent withdrawn by subject	2	-
Adverse event, non-fatal	5	3
Eligibility Violation	1	-
Non-Compliance With Study Drug	2	-
On-going in Study	8	20

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 + Baseline Treatment, then Satralizumab

Arm description

Participants received matching placebo, subcutaneous (SC) at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period (up to approximately 216 weeks), all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD). At the CCOD, participants who had not experienced a relapse during the DB period were invited to initiate satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Arm type

Placebo

Investigational medicinal product name

Baseline treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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 (Q4W).

Satralizumab + Baseline Treatment, then Satralizumab

Arm description

Participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter throughout the DB period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period (up to approximately 216 weeks), all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the CCOD. At the CCOD, participants who had not experienced a relapse during the DB period were invited to continue satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Arm type

Experimental

Investigational medicinal product name

Baseline treatment

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Satralizumab

Investigational medicinal product code

Other name

SA237, RG6168, RO5333787

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

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

Number of subjects in period 2	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Started	24	18
Completed	0	0
Not completed	24	18
Consent withdrawn by subject	-	2
Adverse event, non-fatal	2	1
On-going in Study	19	14
Non-Compliance With Study Drug	-	1
Lack of efficacy	3	-

Baseline characteristics

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Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab	Total
Number of subjects	42	41
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	43.38 ( 12.03 )	40.78 ( 16.09 )	-
Sex: Female, Male
Units:
Male	2	4	6
Female	40	37	77

End points

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Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Reporting group title

Placebo + Baseline Treatment, then Satralizumab

Reporting group description

Participants received matching placebo, subcutaneous (SC) at Weeks 0, 2 and 4, and every 4 weeks (Q4W) thereafter throughout the double-blind (DB) period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period (up to approximately 216 weeks), all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD). At the CCOD, participants who had not experienced a relapse during the DB period were invited to initiate satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

Reporting group title

Satralizumab + Baseline Treatment, then Satralizumab

Reporting group description

Participants received satralizumab 120 mg SC injection at Weeks 0, 2 and 4, and Q4W thereafter throughout the DB period up to protocol-defined relapse or treated relapse in addition to baseline treatment. Following the DB period (up to approximately 216 weeks), all participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the CCOD. At the CCOD, participants who had not experienced a relapse during the DB period were invited to continue satralizumab 120 mg SC injection (with or without baseline treatment at Weeks 0, 2 and 4, and Q4W thereafter) after 4 weeks from their last study treatment dose in the DB period.

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

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End point title

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

End point description

TFR was defined as time from randomization to first occurrence of relapse in the DB period. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological NMO or NMOSD as adjudicated by an independent clinical endpoint committee (CEC). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had onset days that were 30 days of one another, they were counted only as 1 relapse), and onset date used in analysis was the date of first relapse. ITT population. 99999 and 9999999=lower and upper limit of CI were not reached due to low number of participants with events. 999999=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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: weeks
median (confidence interval 95%)	120.6 (37.0 to 9999999)	999999 (99999 to 9999999)

Satralizumab versus Placebo

Statistical analysis description

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

Comparison groups

Placebo + Baseline Treatment, then Satralizumab v Satralizumab + Baseline Treatment, 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

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

0.88

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

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End point title

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

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 baseline observation carried forward (BOCF) method.

End point type

Secondary

End point timeframe

Baseline, Week 24

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

Satralizumab versus Placebo

Statistical analysis description

ANCOVA model: treatment group as fixed effect and baseline measurements, prior therapy, most recent attack (first attack/relapse) as covariates

Comparison groups

Placebo + Baseline Treatment, then Satralizumab v Satralizumab + Baseline Treatment, then Satralizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0602

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.376

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

13.033

Variability estimate

Standard error of the mean

Dispersion value

3.344

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

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End point title

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

End point description

The FACIT Fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. As each of the 13 items of the scale ranges from 0-4, the range of possible scores was computed using FACIT scoring algorithm as 0-52, where 0 is the worst possible score and 52 the best which indicated less fatigue. A positive change from baseline indicates an improvement. ANCOVA was used for analysis to report the adjusted mean and SE. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard error)
Baseline	33.857 ( 1.746 )	34.732 ( 1.646 )
Change from Baseline to Week 24	2.234 ( 0.943 )	0.145 ( 0.963 )

Satralizumab versus Placebo

Statistical analysis description

ANCOVA model: treatment group as fixed effect and baseline measurements, prior therapy, most recent attack (first attack/relapse) as covariates

Comparison groups

Placebo + Baseline Treatment, then Satralizumab v Satralizumab + Baseline Treatment, then Satralizumab

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1224

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.089

Confidence interval

level

95%

sides

2-sided

lower limit

-4.752

upper limit

0.574

Variability estimate

Standard error of the mean

Dispersion value

1.338

Secondary: Relapse-Free Rate During the DB Period

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End point title

Relapse-Free Rate During the DB Period

End point description

Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (i.e., if 2 relapses had 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	34	37
Units: percentage
number (not applicable)
Week 12 (n=34, 37)	89.86	94.99
Week 24 (n=30, 29)	84.41	88.86
Week 36 (n=22, 25)	69.49	88.86
Week 48 (n=19, 24)	66.02	88.86
Week 72 (n=16, 22)	58.68	81.46
Week 96 (n=16, 20)	58.68	77.58
Week 120 (n=12, 19)	54.17	73.70
Week 144 (n=9, 14)	49.24	73.70
Week 168 (n=4, 9)	43.77	73.70
Week 192 (n=0, 2)	6666	73.70
Week 216 (n=0, 1)	6666	73.70

No statistical analyses for this end point

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

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End point title

Annualized Relapse Rate (ARR) During the DB Period

End point description

The ARR is calculated as the total number of participants with relapses experienced divided by the patient-years at risk. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neurological NMO or NMOSD. Symptoms had to persist for >24 hours and not be attributable to confounding clinical factors (e.g., fever, infection, injury, change in mood, adverse reactions to medications). New or worsening neurological symptoms that occurred < 31 days following onset of a protocol-defined relapse were considered part of same relapse (2 relapses with onset days in 30 days of one another was counted as 1 relapse), onset date used in analysis was the date of first relapse. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: patients w relapse/patient-years at risk
number (confidence interval 95%)	0.32 (0.19 to 0.51)	0.11 (0.05 to 0.21)

No statistical analyses for this end point

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

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End point title

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

End point description

The mRS is a 7-point disability scale that assesses the degree of disability in participants with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability. A negative change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	1.55 ( 0.97 )	1.90 ( 1.14 )
Change from Baseline at Week 24 (n=29, 29)	-0.03 ( 0.42 )	-0.03 ( 0.50 )
Change from Baseline at Week 48 (n=17, 24)	-0.18 ( 0.53 )	-0.13 ( 0.45 )
Change from Baseline at Week 72 (n=15, 23)	0.07 ( 0.70 )	0.00 ( 0.52 )
Change from Baseline at Week 96 (n=16, 21)	0.13 ( 0.62 )	-0.19 ( 0.51 )
Change from Baseline at Week 120 (n=10, 20)	-0.10 ( 0.74 )	-0.05 ( 0.51 )
Change from Baseline at Week 144 (n=9, 15)	-0.11 ( 0.93 )	-0.20 ( 0.41 )
Change from Baseline at Week 168 (n=3, 9)	-0.67 ( 0.58 )	-0.11 ( 0.33 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	-0.50 ( 0.71 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	0.00 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The ZBI is the measurement to assess caregiver burden. The 22 items ask for the strain caregivers perceive. Responses range from 0 (never) to 4 (nearly always). The overall ZBI score ranges from 0 to 88. The higher the total score, the heavier the perceived burden. A negative change from baseline indicates an improvement. ITT population included all participants randomized to the treatment groups. 9999=SD was not calculable for 1 participant.

End point type

Secondary

End point timeframe

Baseline up to Week 168

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	16	13
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=16, 13)	19.31 ( 9.31 )	18.92 ( 12.82 )
Change from Baseline at Week 24 (n=9, 7)	-3.44 ( 5.59 )	-3.57 ( 7.11 )
Change from Baseline at Week 48 (n=6, 8)	1.17 ( 8.26 )	1.13 ( 13.45 )
Change from Baseline at Week 72 (n=5, 7)	2.20 ( 19.64 )	-0.71 ( 11.60 )
Change from Baseline at Week 96 (n=5, 6)	3.00 ( 14.98 )	4.17 ( 13.33 )
Change from Baseline at Week 120 (n=3, 5)	0.00 ( 3.61 )	3.40 ( 9.29 )
Change from Baseline at Week 144 (n=2, 4)	-3.50 ( 12.02 )	-3.50 ( 11.33 )
Change from Baseline at Week 168 (n=2, 1)	2.50 ( 13.44 )	11.00 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The EDSS is an ordinal scale with values from 0 points (normal neurological examination) to 10 points (death) increasing in half-point increments once an EDSS of 1.0 has been reached. Higher scores represent increased disability. A negative change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	41	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=41, 41)	3.63 ( 1.32 )	3.83 ( 1.57 )
Change from Baseline at Week 24 (n=29, 29)	-0.21 ( 0.68 )	-0.14 ( 0.82 )
Change from Baseline at Week 48 (n=18, 24)	-0.19 ( 0.77 )	-0.19 ( 0.67 )
Change from Baseline at Week 72 (n=15, 21)	-0.27 ( 0.68 )	-0.29 ( 0.73 )
Change from Baseline at Week 96 (n=16, 21)	-0.19 ( 0.81 )	-0.19 ( 0.75 )
Change from Baseline at Week 120 (n=10, 20)	-0.30 ( 0.79 )	0.03 ( 0.57 )
Change from Baseline at Week 144 (n=9, 15)	-0.33 ( 0.83 )	-0.07 ( 0.62 )
Change from Baseline at Week 168 (n=3, 9)	-0.17 ( 0.76 )	-0.06 ( 0.58 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	0.00 ( 0.71 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	-0.50 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

Visual acuity was measured using Snellen 20-foot wall chart and then converted to logMAR visual acuity scoring. Lower values indicate better visual acuity. Data are reported for right eye (OD) and left eye (OS). A negative change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline: OD (n=42, 41)	0.490 ( 0.928 )	0.303 ( 0.593 )
Baseline: OS (n=42, 41)	0.526 ( 0.911 )	0.597 ( 1.016 )
Change from Baseline at Week 24: OD (n=30, 29)	-0.064 ( 0.197 )	0.042 ( 0.236 )
Change from Baseline at Week 24: OS (n=30, 29)	-0.012 ( 0.107 )	0.059 ( 0.319 )
Change from Baseline at Week 48: OD (n=18, 24)	-0.019 ( 0.086 )	0.008 ( 0.093 )
Change from Baseline at Week 48: OS (n=18, 24)	0.026 ( 0.096 )	0.013 ( 0.061 )
Change from Baseline at Week 72: OD (n=15, 21)	-0.001 ( 0.110 )	-0.034 ( 0.111 )
Change from Baseline at Week 72: OS (n=15, 21)	-0.001 ( 0.121 )	-0.019 ( 0.077 )
Change from Baseline at Week 96: OD (n=16, 21)	0.018 ( 0.174 )	-0.013 ( 0.095 )
Change from Baseline at Week 96: OS (n=16, 21)	-0.078 ( 0.185 )	-0.010 ( 0.073 )
Change from Baseline at Week 120: OD (n=10, 20)	0.030 ( 0.150 )	0.011 ( 0.103 )
Change from Baseline at Week 120: OS (n=10, 20)	-0.024 ( 0.150 )	0.014 ( 0.257 )
Change from Baseline at Week 144: OD (n=9, 15)	0.058 ( 0.231 )	-0.016 ( 0.120 )
Change from Baseline at Week 144: OS (n=9, 15)	-0.016 ( 0.165 )	-0.028 ( 0.111 )
Change from Baseline at Week 168: OD (n=3, 9)	0.113 ( 0.306 )	0.027 ( 0.199 )
Change from Baseline at Week 168: OS (n=3, 9)	0.100 ( 0.173 )	-0.024 ( 0.113 )
Change from Baseline at Week 192: OD (n=0, 2)	6666 ( 6666 )	0.150 ( 0.099 )
Change from Baseline at Week 192: OS (n=0, 2)	6666 ( 6666 )	0.000 ( 0.000 )
Change from Baseline at Week 216: OD (n=0, 1)	6666 ( 6666 )	0.120 ( 9999 )
Change from Baseline at Week 216: OS (n=0, 1)	6666 ( 6666 )	0.000 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health summary measures and a preference-based health utility index. The component scores were transformed to a 0-100 scale, where higher score indicates better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	44.77 ( 11.08 )	44.56 ( 9.75 )
Change from Baseline at Week 24 (n=28, 29)	2.53 ( 7.58 )	0.57 ( 8.99 )
Change from Baseline at Week 48 (n=18, 24)	2.78 ( 7.51 )	-0.61 ( 10.97 )
Change from Baseline at Week 72 (n=15, 23)	3.47 ( 7.13 )	2.78 ( 8.13 )
Change from Baseline at Week 96 (n=16, 21)	5.16 ( 10.52 )	1.06 ( 7.63 )
Change from Baseline at Week 120 (n=10, 20)	3.63 ( 8.62 )	0.71 ( 7.23 )
Change from Baseline at Week 144 (n=9, 15)	2.83 ( 8.79 )	3.82 ( 7.15 )
Change from Baseline at Week 168 (n=3, 9)	2.79 ( 6.85 )	3.60 ( 9.50 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	11.60 ( 7.32 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	14.05 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline up to Week 216

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	41.54 ( 9.11 )	43.60 ( 10.47 )
Change from Baseline at Week 24 (n=28, 29)	2.79 ( 5.61 )	1.30 ( 6.01 )
Change from Baseline at Week 48 (n=18, 24)	0.18 ( 5.33 )	1.22 ( 5.77 )
Change from Baseline at Week 72 (n=15, 23)	1.97 ( 6.23 )	1.16 ( 4.79 )
Change from Baseline at Week 96 (n=16, 21)	-1.15 ( 7.52 )	1.88 ( 5.72 )
Change from Baseline at Week 120 (n=10, 20)	-0.13 ( 7.10 )	2.34 ( 6.60 )
Change from Baseline at Week 144 (n=9, 15)	1.78 ( 5.50 )	3.05 ( 4.23 )
Change from Baseline at Week 168 (n=3, 9)	0.22 ( 9.23 )	0.76 ( 5.98 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	0.23 ( 0.55 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	-1.63 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	43.91 ( 10.22 )	45.94 ( 11.56 )
Change from Baseline at Week 24 (n=29, 29)	2.71 ( 7.06 )	0.03 ( 11.06 )
Change from Baseline at Week 48 (n=18, 24)	0.81 ( 5.60 )	0.12 ( 6.99 )
Change from Baseline at Week 72 (n=15, 23)	3.55 ( 8.20 )	2.30 ( 6.99 )
Change from Baseline at Week 96 (n=16, 21)	1.31 ( 7.13 )	1.15 ( 8.86 )
Change from Baseline at Week 120 (n=10, 20)	2.22 ( 9.96 )	-1.45 ( 9.13 )
Change from Baseline at Week 144 (n=9, 15)	3.58 ( 8.53 )	3.14 ( 8.18 )
Change from Baseline at Week 168 (n=3, 9)	1.61 ( 10.58 )	3.05 ( 9.00 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	8.07 ( 0.57 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	3.63 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	39.65 ( 7.90 )	41.23 ( 9.29 )
Change from Baseline at Week 24 (n=29, 29)	1.84 ( 5.68 )	-0.60 ( 7.26 )
Change from Baseline at Week 48 (n=18, 24)	-0.66 ( 5.53 )	-0.27 ( 6.00 )
Change from Baseline at Week 72 (n=15, 23)	-0.16 ( 6.25 )	0.94 ( 5.57 )
Change from Baseline at Week 96 (n=16, 21)	-1.90 ( 6.17 )	1.86 ( 6.12 )
Change from Baseline at Week 120 (n=10, 20)	-0.33 ( 4.03 )	3.76 ( 6.72 )
Change from Baseline at Week 144 (n=9, 15)	-0.95 ( 5.66 )	5.20 ( 7.11 )
Change from Baseline at Week 168 (n=3, 9)	-5.23 ( 7.41 )	3.06 ( 6.99 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	1.19 ( 5.04 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	-2.38 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	43.71 ( 10.92 )	43.59 ( 10.55 )
Change from Baseline at Week 24 (n=29, 29)	5.23 ( 7.69 )	0.99 ( 10.21 )
Change from Baseline at Week 48 (n=18, 24)	2.76 ( 8.54 )	0.11 ( 10.73 )
Change from Baseline at Week 72 (n=15, 23)	5.23 ( 7.66 )	3.18 ( 9.72 )
Change from Baseline at Week 96 (n=16, 21)	4.09 ( 8.49 )	2.12 ( 8.13 )
Change from Baseline at Week 120 (n=10, 20)	3.14 ( 7.06 )	1.57 ( 6.76 )
Change from Baseline at Week 144 (n=9, 15)	3.49 ( 7.04 )	4.88 ( 8.38 )
Change from Baseline at Week 168 (n=3, 9)	4.36 ( 3.02 )	4.07 ( 10.72 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	13.09 ( 14.80 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	23.55 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	42.50 ( 10.53 )	43.46 ( 10.34 )
Change from Baseline at Week 24 (n=29, 29)	3.56 ( 7.04 )	1.49 ( 7.05 )
Change from Baseline at Week 48 (n=18, 24)	1.92 ( 4.30 )	1.86 ( 7.73 )
Change from Baseline at Week 72 (n=15, 23)	3.19 ( 6.54 )	0.88 ( 6.52 )
Change from Baseline at Week 96 (n=16, 21)	0.84 ( 6.77 )	2.37 ( 7.75 )
Change from Baseline at Week 120 (n=10, 20)	-0.19 ( 8.39 )	2.58 ( 6.03 )
Change from Baseline at Week 144 (n=9, 15)	2.55 ( 4.06 )	3.32 ( 5.72 )
Change from Baseline at Week 168 (n=3, 9)	1.92 ( 5.06 )	0.00 ( 5.50 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	1.91 ( 2.70 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	1.91 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	43.98 ( 11.46 )	43.01 ( 10.55 )
Change from Baseline at Week 24 (n=28, 29)	2.24 ( 10.35 )	0.36 ( 10.12 )
Change from Baseline at Week 48 (n=18, 24)	3.29 ( 8.05 )	0.00 ( 12.49 )
Change from Baseline at Week 72 (n=15, 23)	1.39 ( 9.38 )	2.57 ( 7.66 )
Change from Baseline at Week 96 (n=16, 21)	4.13 ( 14.40 )	0.83 ( 10.20 )
Change from Baseline at Week 120 (n=10, 20)	3.13 ( 12.44 )	0.35 ( 6.95 )
Change from Baseline at Week 144 (n=9, 15)	3.09 ( 9.61 )	3.25 ( 7.38 )
Change from Baseline at Week 168 (n=3, 9)	1.16 ( 5.32 )	4.64 ( 9.05 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	12.19 ( 2.46 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	6.97 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	40.74 ( 10.12 )	41.88 ( 11.38 )
Change from Baseline at Week 24 (n=28, 29)	3.93 ( 9.56 )	3.02 ( 6.95 )
Change from Baseline at Week 48 (n=18, 24)	1.37 ( 7.23 )	1.40 ( 8.66 )
Change from Baseline at Week 72 (n=15, 23)	2.40 ( 7.94 )	2.83 ( 7.81 )
Change from Baseline at Week 96 (n=16, 21)	0.42 ( 9.03 )	1.71 ( 4.60 )
Change from Baseline at Week 120 (n=10, 20)	1.57 ( 9.47 )	3.14 ( 7.44 )
Change from Baseline at Week 144 (n=9, 15)	2.99 ( 6.05 )	2.69 ( 6.80 )
Change from Baseline at Week 168 (n=3, 9)	3.74 ( 10.61 )	2.25 ( 6.45 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	4.49 ( 6.35 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	8.98 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	41.70 ( 11.62 )	44.26 ( 10.92 )
Change from Baseline at Week 24 (n=29, 29)	1.73 ( 7.96 )	0.86 ( 8.69 )
Change from Baseline at Week 48 (n=18, 24)	1.12 ( 7.80 )	0.00 ( 10.24 )
Change from Baseline at Week 72 (n=15, 23)	2.34 ( 7.78 )	2.18 ( 7.22 )
Change from Baseline at Week 96 (n=16, 21)	2.82 ( 11.72 )	0.00 ( 9.38 )
Change from Baseline at Week 120 (n=10, 20)	1.51 ( 13.59 )	0.25 ( 9.13 )
Change from Baseline at Week 144 (n=9, 15)	0.56 ( 9.85 )	2.01 ( 7.29 )
Change from Baseline at Week 168 (n=3, 9)	1.67 ( 22.61 )	0.00 ( 5.61 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	0.00 ( 0.00 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	-5.01 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The SF-36v2 is a multi-purpose, short form health survey with 36 questions. It has 8 domains (vitality, physical functioning, bodily pain, general health, role-physical, role emotional, social role functioning and mental health) of functional health and well-being scores as well as psychometrically based physical and mental health component summary measures and a preference-based health utility index. The domain scores were transformed to a 0-100 scale, where higher scores indicate better quality of life. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 41)	45.95 ( 9.14 )	46.66 ( 9.65 )
Change from Baseline at Week 24 (n=29, 29)	2.66 ( 7.38 )	1.74 ( 8.61 )
Change from Baseline at Week 48 (n=18, 24)	1.65 ( 5.60 )	-0.25 ( 8.71 )
Change from Baseline at Week 72 (n=15, 23)	4.55 ( 6.91 )	1.38 ( 9.12 )
Change from Baseline at Week 96 (n=16, 21)	4.08 ( 8.53 )	2.41 ( 8.28 )
Change from Baseline at Week 120 (n=10, 20)	2.97 ( 5.24 )	2.67 ( 8.45 )
Change from Baseline at Week 144 (n=9, 15)	3.96 ( 6.12 )	4.16 ( 10.03 )
Change from Baseline at Week 168 (n=3, 9)	2.97 ( 2.97 )	0.99 ( 10.82 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	7.43 ( 10.51 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	11.89 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

The EQ-5D is a participant-answered questionnaire measuring 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with 3 possible response categories: 1) no problems; 2) some problems; 3) severe problems. The scores from 5 dimensions are used as input to generate EQ-5D index score using scoring algorithm. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state. A positive change from baseline indicates an improvement. 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 + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	40
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=42, 40)	0.7297 ( 0.1863 )	0.7634 ( 0.1811 )
Change from Baseline at Week 24 (n=29, 28)	0.0649 ( 0.1596 )	-0.0082 ( 0.1882 )
Change from Baseline at Week 48 (n=18, 23)	0.0352 ( 0.1830 )	0.0011 ( 0.1256 )
Change from Baseline at Week 72 (n=15, 22)	0.0724 ( 0.2088 )	0.0241 ( 0.1084 )
Change from Baseline at Week 96 (n=16, 20)	0.0349 ( 0.1758 )	0.0167 ( 0.1056 )
Change from Baseline at Week 120 (n=10, 19)	0.0336 ( 0.2111 )	0.0257 ( 0.1178 )
Change from Baseline at Week 144 (n=9, 15)	0.0846 ( 0.1650 )	0.0488 ( 0.1424 )
Change from Baseline at Week 168 (n=3, 9)	0.0648 ( 0.1031 )	0.0307 ( 0.1335 )
Change from Baseline at Week 192 (n=0, 2)	6666 ( 6666 )	0.1873 ( 0.2890 )
Change from Baseline at Week 216 (n=0, 1)	6666 ( 6666 )	0.3322 ( 9999 )

No statistical analyses for this end point

Secondary: Serum Satralizumab Concentration During the DB Period

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End point title

Serum Satralizumab Concentration During the DB Period ^[1]

End point description

The safety analysis population (SAF) included all randomized participants who had received at least 1 dose of satralizumab or placebo. 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 224

Notes
[1] - 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: The endpoint reports data only for the arm treated with satralizumab.

End point values	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	41
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (n=40)	100.00 ( 0.00 )
Week 2 (n=41)	11343.66 ( 5125.84 )
Week 4 (n=38)	22222.63 ( 8003.48 )
Week 5 (n=20)	28461.00 ( 12542.52 )
Week 6 (n=20)	28174.50 ( 11199.00 )
Week 8 (n=39)	21246.92 ( 9045.31 )
Week 12 (n=38)	20927.63 ( 9536.07 )
Week 16 (n=35)	20274.86 ( 10694.38 )
Week 20 (n=33)	20146.06 ( 10740.65 )
Week 24 (n=30)	20189.00 ( 10140.88 )
Week 28 (n=28)	20826.07 ( 10995.92 )
Week 32 (n=28)	20631.79 ( 11110.94 )
Week 36 (n=26)	21114.62 ( 11190.52 )
Week 40 (n=25)	22224.76 ( 13389.71 )
Week 44 (n=23)	22582.17 ( 12031.13 )
Week 48 (n=25)	23324.80 ( 13979.87 )
Week 52 (n=24)	24570.83 ( 15798.38 )
Week 56 (n=24)	24252.50 ( 15433.80 )
Week 60 (n=24)	23061.67 ( 15777.82 )
Week 64 (n=22)	23369.55 ( 13447.96 )
Week 68 (n=23)	26194.43 ( 16836.77 )
Week 72 (n=23)	26618.87 ( 14999.38 )
Week 76 (n=22)	26539.09 ( 13736.30 )
Week 80 (n=21)	26868.00 ( 14005.87 )
Week 84 (n=21)	27037.62 ( 15460.97 )
Week 88 (n=20)	26203.00 ( 14309.81 )
Week 92 (n=21)	28308.10 ( 15111.34 )
Week 96 (n=21)	26754.43 ( 15146.20 )
Week 100 (n=21)	27707.14 ( 14225.93 )
Week 104 (n=21)	26203.81 ( 13616.28 )
Week 108 (n=21)	26112.38 ( 12521.65 )
Week 112 (n=21)	24925.10 ( 12181.81 )
Week 116 (n=20)	26360.50 ( 13885.76 )
Week 120 (n=20)	24910.00 ( 13217.57 )
Week 124 (n=20)	24689.50 ( 14352.30 )
Week 128 (n=19)	22395.53 ( 12954.00 )
Week 132 (n=19)	23804.74 ( 14878.32 )
Week 136 (n=19)	25856.32 ( 15506.85 )
Week 140 (n=18)	26118.56 ( 15264.89 )
Week 144 (n=15)	27975.33 ( 11536.28 )
Week 148 (n=12)	27935.83 ( 11940.90 )
Week 152 (n=10)	28967.00 ( 10354.22 )
Week 156 (n=9)	27990.00 ( 10444.75 )
Week 160 (n=9)	28983.33 ( 11429.02 )
Week 164 (n=9)	28903.33 ( 10780.69 )
Week 168 (n=9)	23683.33 ( 11615.40 )
Week 172 (n=9)	24498.89 ( 11106.23 )
Week 176 (n=9)	26300.00 ( 11498.48 )
Week 180 (n=6)	28300.00 ( 9431.86 )
Week 184 (n=5)	32380.00 ( 9427.19 )
Week 188 (n=3)	36600.00 ( 8214.62 )
Week 192 (n=2)	32650.00 ( 7848.89 )
Week 196 (n=2)	30800.00 ( 4808.33 )
Week 200 (n=2)	28400.00 ( 3818.38 )
Week 204 (n=2)	25300.00 ( 3252.69 )
Week 208 (n=1)	25900.00 ( 9999 )
Week 212 (n=1)	17000.00 ( 9999 )
Week 216 (n=1)	28600.00 ( 9999 )
Week 220 (n=1)	31600.00 ( 9999 )
Week 224 (n=1)	28700.00 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

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 224

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: ng/mL
arithmetic mean (standard deviation)
Baseline (n=42, 40)	32.52 ( 7.78 )	35.13 ( 21.52 )
Week 2 (n=41, 41)	33.82 ( 8.30 )	437.41 ( 72.31 )
Week 4 (n=40, 41)	33.13 ( 8.52 )	572.29 ( 94.84 )
Week 8 (n=37, 39)	34.02 ( 9.43 )	642.92 ( 115.51 )
Week 12 (n=33, 39)	32.58 ( 8.52 )	651.41 ( 99.20 )
Week 16 (n=32, 35)	32.67 ( 9.32 )	640.57 ( 97.41 )
Week 20 (n=31, 33)	34.22 ( 8.15 )	636.64 ( 109.75 )
Week 24 (n=30, 30)	34.44 ( 9.31 )	639.20 ( 108.94 )
Week 28 (n=26, 28)	33.70 ( 8.28 )	649.11 ( 131.85 )
Week 32 (n=24, 28)	33.48 ( 8.74 )	651.82 ( 162.04 )
Week 36 (n=23, 26)	34.39 ( 11.01 )	652.12 ( 124.70 )
Week 40 (n=19, 24)	33.31 ( 7.86 )	664.21 ( 158.61 )
Week 44 (n=18, 23)	33.94 ( 7.77 )	677.13 ( 173.99 )
Week 48 (n=18, 25)	34.50 ( 9.14 )	627.23 ( 217.06 )
Week 52 (n=18, 24)	44.01 ( 44.26 )	656.29 ( 173.67 )
Week 56 (n=18, 24)	37.00 ( 7.42 )	626.83 ( 155.56 )
Week 60 (n=18, 24)	36.39 ( 7.81 )	617.00 ( 142.13 )
Week 64 (n=17, 22)	35.14 ( 8.78 )	621.27 ( 152.45 )
Week 68 (n=17, 23)	35.35 ( 8.68 )	664.91 ( 130.58 )
Week 72 (n=15, 23)	36.02 ( 10.73 )	648.83 ( 134.32 )
Week 76 (n=16, 22)	36.94 ( 9.46 )	643.91 ( 118.60 )
Week 80 (n=16, 21)	36.45 ( 9.50 )	667.24 ( 133.49 )
Week 84 (n=16, 21)	34.60 ( 8.88 )	649.38 ( 137.64 )
Week 88 (n=13, 20)	31.95 ( 8.29 )	651.35 ( 150.58 )
Week 92 (n=16, 21)	34.30 ( 9.71 )	633.43 ( 134.36 )
Week 96 (n=16, 21)	32.88 ( 9.39 )	630.62 ( 162.28 )
Week 100 (n=15, 21)	33.78 ( 9.04 )	651.90 ( 162.09 )
Week 104 (n=14, 21)	31.61 ( 9.13 )	649.57 ( 185.99 )
Week 108 (n=13, 21)	31.49 ( 9.23 )	658.67 ( 152.61 )
Week 112 (n=12, 21)	32.75 ( 7.77 )	683.90 ( 135.07 )
Week 116 (n=13, 20)	33.68 ( 8.31 )	653.98 ( 194.92 )
Week 120 (n=12, 20)	33.73 ( 6.20 )	667.10 ( 152.24 )
Week 124 (n=10, 20)	33.06 ( 9.31 )	696.45 ( 138.17 )
Week 128 (n=10, 19)	34.07 ( 8.83 )	670.05 ( 138.28 )
Week 132 (n=10, 19)	34.28 ( 4.95 )	671.84 ( 138.75 )
Week 136 (n=10, 19)	32.43 ( 8.12 )	674.95 ( 170.04 )
Week 140 (n=10, 18)	32.97 ( 6.52 )	645.72 ( 132.32 )
Week 144 (n=9, 15)	35.37 ( 8.91 )	699.80 ( 101.84 )
Week 148 (n=7, 12)	37.97 ( 12.40 )	672.42 ( 107.40 )
Week 152 (n=5, 10)	35.08 ( 9.08 )	701.60 ( 110.27 )
Week 156 (n=5, 9)	36.92 ( 7.77 )	720.33 ( 103.58 )
Week 160 (n=4, 9)	40.38 ( 7.31 )	704.89 ( 109.86 )
Week 164 (n=4, 9)	43.08 ( 10.54 )	723.67 ( 136.20 )
Week 168 (n=3, 9)	42.30 ( 5.92 )	744.22 ( 123.47 )
Week 172 (n=3, 9)	42.03 ( 5.87 )	706.33 ( 127.63 )
Week 176 (n=2, 9)	39.85 ( 6.15 )	730.56 ( 121.75 )
Week 180 (n=2, 6)	38.85 ( 12.09 )	769.83 ( 119.50 )
Week 184 (n=0, 5)	6666 ( 6666 )	736.80 ( 152.09 )
Week 188 (n=0, 3)	6666 ( 6666 )	853.67 ( 38.02 )
Week 192 (n=0, 2)	6666 ( 6666 )	930.00 ( 49.50 )
Week 196 (n=0, 2)	6666 ( 6666 )	887.00 ( 91.92 )
Week 200 (n=0, 2)	6666 ( 6666 )	902.50 ( 79.90 )
Week 204 (n=0, 2)	6666 ( 6666 )	935.00 ( 7.07 )
Week 208 (n=0, 1)	6666 ( 6666 )	941.00 ( 9999 )
Week 212 (n=0, 1)	6666 ( 6666 )	971.00 ( 9999 )
Week 216 (n=0, 1)	6666 ( 6666 )	896.00 ( 9999 )
Week 220 (n=0, 1)	6666 ( 6666 )	901.00 ( 9999 )
Week 224 (n=0, 1)	6666 ( 6666 )	831.00 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

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 224

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: mg/L
arithmetic mean (standard deviation)
Baseline (n=42, 41)	1.48 ( 2.08 )	1.68 ( 2.49 )
Week 2 (n=41, 40)	1.65 ( 2.86 )	0.78 ( 2.93 )
Week 4 (n=40, 41)	1.59 ( 2.27 )	0.44 ( 0.72 )
Week 8 (n=37, 39)	1.76 ( 2.25 )	0.59 ( 1.26 )
Week 12 (n=33, 38)	1.48 ( 2.07 )	0.47 ( 0.60 )
Week 16 (n=32, 35)	1.91 ( 3.34 )	0.49 ( 0.51 )
Week 20 (n=31, 33)	1.91 ( 3.44 )	0.48 ( 0.50 )
Week 24 (n=30, 30)	2.45 ( 6.87 )	0.58 ( 0.91 )
Week 28 (n=26, 28)	1.96 ( 3.24 )	0.73 ( 1.34 )
Week 32 (n=24, 28)	2.36 ( 4.96 )	0.73 ( 1.21 )
Week 36 (n=23, 26)	2.48 ( 3.59 )	0.56 ( 0.66 )
Week 40 (n=19, 25)	2.49 ( 4.53 )	1.13 ( 2.26 )
Week 44 (n=18, 23)	1.41 ( 1.47 )	0.72 ( 1.20 )
Week 48 (n=18, 25)	1.59 ( 2.07 )	0.86 ( 1.44 )
Week 52 (n=18, 24)	2.60 ( 3.87 )	0.67 ( 0.88 )
Week 56 (n=18, 23)	1.43 ( 1.58 )	0.72 ( 1.02 )
Week 60 (n=18, 24)	2.63 ( 4.34 )	1.05 ( 2.15 )
Week 64 (n=17, 22)	11.10 ( 40.09 )	0.64 ( 0.89 )
Week 68 (n=17, 23)	1.86 ( 2.66 )	0.57 ( 0.47 )
Week 72 (n=15, 23)	3.80 ( 8.83 )	0.59 ( 0.71 )
Week 76 (n=15, 22)	5.24 ( 10.68 )	0.51 ( 0.37 )
Week 80 (n=16, 21)	2.11 ( 2.63 )	0.58 ( 0.51 )
Week 84 (n=16, 21)	2.08 ( 2.26 )	0.59 ( 0.61 )
Week 88 (n=14, 20)	5.19 ( 12.83 )	0.60 ( 0.53 )
Week 92 (n=16, 21)	2.07 ( 2.21 )	0.60 ( 0.70 )
Week 96 (n=16, 20)	2.92 ( 4.60 )	0.74 ( 1.01 )
Week 100 (n=15, 21)	2.58 ( 4.53 )	0.87 ( 1.49 )
Week 104 (n=14, 21)	1.41 ( 2.05 )	0.84 ( 1.40 )
Week 108 (n=13, 21)	1.93 ( 2.25 )	0.66 ( 0.58 )
Week 112 (n=12, 21)	1.54 ( 1.56 )	0.82 ( 0.87 )
Week 116 (n=13, 20)	2.39 ( 3.91 )	0.84 ( 1.26 )
Week 120 (n=12, 20)	1.53 ( 1.33 )	0.98 ( 1.58 )
Week 124 (n=10, 20)	1.43 ( 1.43 )	0.72 ( 0.67 )
Week 128 (n=10, 19)	6.00 ( 16.28 )	0.96 ( 1.29 )
Week 132 (n=10, 19)	1.08 ( 0.94 )	0.70 ( 0.84 )
Week 136 (n=10, 19)	1.43 ( 1.54 )	0.99 ( 1.68 )
Week 140 (n=10, 18)	1.15 ( 1.28 )	1.06 ( 2.25 )
Week 144 (n=9, 15)	0.82 ( 0.73 )	0.44 ( 0.37 )
Week 148 (n=7, 12)	1.29 ( 1.43 )	0.35 ( 0.18 )
Week 152 (n=5, 10)	1.08 ( 0.97 )	0.38 ( 0.23 )
Week 156 (n=5, 9)	1.52 ( 1.42 )	0.35 ( 0.18 )
Week 160 (n=4, 9)	0.83 ( 0.53 )	0.37 ( 0.22 )
Week 164 (n=4, 9)	3.18 ( 4.89 )	0.38 ( 0.20 )
Week 168 (n=3, 9)	0.80 ( 0.26 )	0.40 ( 0.19 )
Week 172 (n=3, 8)	1.37 ( 1.00 )	0.26 ( 0.17 )
Week 176 (n=2, 8)	0.95 ( 0.64 )	0.31 ( 0.19 )
Week 180 (n=2, 6)	30.15 ( 41.65 )	0.28 ( 0.15 )
Week 184 (n=0, 5)	6666 ( 6666 )	0.20 ( 0.11 )
Week 188 (n=0, 3)	6666 ( 6666 )	0.37 ( 0.06 )
Week 192 (n=0, 2)	6666 ( 6666 )	0.15 ( 0.00 )
Week 196 (n=0, 2)	6666 ( 6666 )	0.23 ( 0.11 )
Week 200 (n=0, 2)	6666 ( 6666 )	0.23 ( 0.11 )
Week 204 (n=0, 2)	6666 ( 6666 )	0.23 ( 0.11 )
Week 208 (n=0, 1)	6666 ( 6666 )	0.30 ( 9999 )
Week 212 (n=0, 1)	6666 ( 6666 )	0.40 ( 9999 )
Week 216 (n=0, 1)	6666 ( 6666 )	0.30 ( 9999 )
Week 220 (n=0, 1)	6666 ( 6666 )	0.40 ( 9999 )
Week 224 (n=0, 1)	6666 ( 6666 )	0.15 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

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 224

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	42	41
Units: pg/mL
arithmetic mean (standard deviation)
Baseline (n=42, 40)	1.63 ( 0.39 )	1.92 ( 1.36 )
Week 2 (n=41, 41)	1.84 ( 0.95 )	40.12 ( 118.83 )
Week 4 (n=40, 41)	2.33 ( 2.99 )	28.30 ( 31.31 )
Week 8 (n=37, 38)	1.69 ( 0.55 )	32.37 ( 77.99 )
Week 12 (n=33, 39)	1.71 ( 0.60 )	22.95 ( 20.55 )
Week 16 (n=32, 35)	1.84 ( 0.90 )	25.76 ( 30.85 )
Week 20 (n=31, 33)	2.99 ( 5.45 )	23.07 ( 15.37 )
Week 24 (n=30, 29)	2.02 ( 1.52 )	21.53 ( 17.91 )
Week 28 (n=26, 28)	1.95 ( 1.38 )	25.14 ( 24.27 )
Week 32 (n=24, 28)	1.74 ( 0.84 )	23.77 ( 18.53 )
Week 36 (n=23, 26)	2.13 ( 1.41 )	23.08 ( 15.56 )
Week 40 (n=19, 24)	1.66 ( 0.40 )	27.31 ( 47.45 )
Week 44 (n=17, 21)	1.57 ( 0.00 )	17.01 ( 15.38 )
Week 48 (n=18, 25)	1.69 ( 0.53 )	19.45 ( 19.36 )
Week 52 (n=18, 24)	2.12 ( 1.36 )	21.11 ( 17.42 )
Week 56 (n=18, 22)	1.57 ( 0.00 )	21.74 ( 20.96 )
Week 60 (n=18, 23)	2.27 ( 1.46 )	23.25 ( 23.36 )
Week 64 (n=17, 22)	2.46 ( 3.22 )	24.31 ( 20.74 )
Week 68 (n=17, 23)	1.94 ( 1.14 )	31.30 ( 53.79 )
Week 72 (n=15, 23)	1.93 ( 0.97 )	24.69 ( 24.45 )
Week 76 (n=16, 21)	2.21 ( 1.87 )	20.45 ( 13.79 )
Week 80 (n=16, 21)	2.19 ( 2.51 )	23.29 ( 19.64 )
Week 84 (n=16, 21)	2.66 ( 2.36 )	22.71 ( 21.49 )
Week 88 (n=12, 20)	2.59 ( 2.77 )	29.17 ( 25.58 )
Week 92 (n=16, 20)	1.84 ( 0.77 )	24.51 ( 32.02 )
Week 96 (n=16, 21)	3.06 ( 3.19 )	21.52 ( 20.20 )
Week 100 (n=15, 21)	2.04 ( 1.02 )	21.77 ( 24.98 )
Week 104 (n=13, 21)	1.95 ( 0.96 )	22.61 ( 26.55 )
Week 108 (n=13, 21)	1.76 ( 0.70 )	24.18 ( 20.55 )
Week 112 (n=12, 21)	1.57 ( 0.00 )	32.18 ( 36.15 )
Week 116 (n=13, 20)	1.57 ( 0.00 )	22.33 ( 22.20 )
Week 120 (n=12, 20)	1.71 ( 0.52 )	21.86 ( 24.54 )
Week 124 (n=9, 19)	1.57 ( 0.00 )	26.23 ( 27.67 )
Week 128 (n=10, 19)	1.57 ( 0.00 )	25.40 ( 31.20 )
Week 132 (n=10, 19)	1.57 ( 0.00 )	25.48 ( 27.38 )
Week 136 (n=10, 19)	1.57 ( 0.00 )	27.23 ( 37.56 )
Week 140 (n=10, 18)	1.57 ( 0.00 )	20.66 ( 18.10 )
Week 144 (n=9, 15)	1.57 ( 0.00 )	16.82 ( 16.16 )
Week 148 (n=7, 12)	2.04 ( 1.25 )	17.10 ( 11.33 )
Week 152 (n=5, 10)	1.57 ( 0.00 )	16.62 ( 13.75 )
Week 156 (n=5, 8)	2.34 ( 1.72 )	12.67 ( 5.73 )
Week 160 (n=4, 9)	1.96 ( 0.80 )	11.15 ( 5.12 )
Week 164 (n=4, 9)	1.57 ( 0.00 )	12.84 ( 6.93 )
Week 168 (n=3, 9)	1.57 ( 0.00 )	13.30 ( 8.89 )
Week 172 (n=3, 9)	1.57 ( 0.00 )	13.89 ( 6.94 )
Week 176 (n=2, 9)	1.57 ( 0.00 )	15.11 ( 7.16 )
Week 180 (n=2, 6)	1.57 ( 0.00 )	13.34 ( 6.68 )
Week 184 (n=0, 5)	6666 ( 6666 )	15.24 ( 9.91 )
Week 188 (n=0, 3)	6666 ( 6666 )	13.96 ( 9.74 )
Week 192 (n=0, 2)	6666 ( 6666 )	16.71 ( 13.15 )
Week 196 (n=0, 2)	6666 ( 6666 )	14.34 ( 12.81 )
Week 200 (n=0, 2)	6666 ( 6666 )	18.55 ( 8.84 )
Week 204 (n=0, 2)	6666 ( 6666 )	18.24 ( 12.53 )
Week 208 (n=0, 1)	6666 ( 6666 )	9.95 ( 9999 )
Week 212 (n=0, 1)	6666 ( 6666 )	8.02 ( 9999 )
Week 216 (n=0, 1)	6666 ( 6666 )	6.45 ( 9999 )
Week 220 (n=0, 1)	6666 ( 6666 )	45.80 ( 9999 )
Week 224 (n=0, 1)	6666 ( 6666 )	34.30 ( 9999 )

No statistical analyses for this end point

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

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End point title

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

End point description

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events. 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 224

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

No statistical analyses for this end point

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

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End point title

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

End point description

A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above. 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 224

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

No statistical analyses for this end point

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

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End point title

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

End point description

Non-serious adverse events of special interest for this study included: 1) cases of an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, 2) suspected transmission of an infectious agent by the study treatment. 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 224

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

No statistical analyses for this end point

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

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End point title

Number of Participants with Selected Adverse Events in the DB Period

End point description

Selected adverse events for this study included: 1) non-serious infections that required treatments with intravenous (IV) antibiotic, antifungal, antiviral, 2) opportunistic infections that required treatments with oral antibiotics, antifungals, or antivirals, 3) injection-related reactions (IRRs; an AE which occured within 24 hours after study treatment injection except where the event was not considered an allergic reaction), and 4) anaphylaxis (an acute allergic/hypersensitivity reaction). 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 224

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

No statistical analyses for this end point

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

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End point title

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

End point description

The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior. 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 224)

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	41	41
Units: participants
Baseline (n=41, 40)	5	12
Post-Baseline (n=41, 41)	2	3

No statistical analyses for this end point

Secondary: Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time

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End point title

Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time

End point description

Drift in the anti-AQP4 antibody titer cell-based assay over time confounded longitudinal assessment of anti-AQP4 antibody titers and therefore these results cannot be reported.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period; every 24 weeks for first 48 weeks of open-label extension period (up to approximately 7 years)

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	0 ^[2]	0 ^[3]
Units: Units/mL
arithmetic mean (standard deviation)	( )	( )

Notes
[2] - Longitudinal assessments of anti-AQP4 Ab titers were confounded and data are therefore not reported.
[3] - Longitudinal assessments of anti-AQP4 Ab titers were confounded and data are therefore not reported.

No statistical analyses for this end point

Secondary: Percentage of Blood Plasmablast Over Time

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End point title

Percentage of Blood Plasmablast Over Time

End point description

The plasmablast assay lacked the sensitivity required to measure plasmablast levels at baseline in the majority of participants. Since most participants had plasmablast values below lower limit of quantitation (LLOQ) at baseline, longitudinal assessments could not be performed and therefore plasmablast results are not reported.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 24, 48 and every 24 weeks thereafter of double-blind period (up to approximately 30 months)

End point values	Placebo + Baseline Treatment, then Satralizumab	Satralizumab + Baseline Treatment, then Satralizumab
Number of subjects analysed	0 ^[4]	0 ^[5]
Units: percentage of plasmablasts
arithmetic mean (standard deviation)	( )	( )

Notes
[4] - Due to lack of sensitivity of the plasmablast assay results are not reported.
[5] - Due to lack of sensitivity of the plasmablast assay results are not reported.

No statistical analyses for this end point

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

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End point title

Percentage of Participants with Anti-Drug Antibodies to Satralizumab in the DB Period ^[6]

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.

End point type

Secondary

End point timeframe

Up to approximately Week 224

Notes
[6] - 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: The endpoint reports data only for the arm treated with satralizumab.

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

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to clinical cut-off date, 06 June 2018 (up to approximately 224 weeks).

Adverse event reporting additional description

The SAF included all randomized participants who had received at least 1 dose of satralizumab or placebo.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Placebo + Baseline Treatment, DB Period

Reporting group description

Reporting group title

Placebo, then Satralizumab, OLE Period

Reporting group description

Following placebo treatment in the DB period participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the clinical cut-off date (CCOD).

Reporting group title

Satralizumab, then Satralizumab, OLE Period

Reporting group description

Following satralizumab treatment in the DB period participants received satralizumab 120 mg SC injection (with or without baseline treatment) at Weeks 0, 2 and 4, and Q4W thereafter up to the CCOD.

Reporting group title

Satralizumab + Baseline Treatment, DB Period

Reporting group description

Serious adverse events	Placebo + Baseline Treatment, DB Period	Placebo, then Satralizumab, OLE Period	Satralizumab, then Satralizumab, OLE Period	Satralizumab + Baseline Treatment, DB Period
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 42 (21.43%)	6 / 24 (25.00%)	5 / 18 (27.78%)	7 / 41 (17.07%)
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)
Breast cancer
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (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
Hepatic cancer
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (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
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
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
Spinal compression fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (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
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (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
Parkinsonism
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (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
Tension headache
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia macrocytic
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
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
Autoimmune thrombocytopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphopenia
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Gait disturbance
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (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
Eye disorders
Glaucoma
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal vein thrombosis
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (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
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (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
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
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 polyp
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
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
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (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
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (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
Endocarditis
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (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
Enterocolitis infectious
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis E
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (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
Influenza
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (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
Pneumonia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
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
Urinary tract infection
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (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

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

Non-serious adverse events	Placebo + Baseline Treatment, DB Period	Placebo, then Satralizumab, OLE Period	Satralizumab, then Satralizumab, OLE Period	Satralizumab + Baseline Treatment, DB Period
Total subjects affected by non serious adverse events
subjects affected / exposed	36 / 42 (85.71%)	23 / 24 (95.83%)	16 / 18 (88.89%)	33 / 41 (80.49%)
Vascular disorders
Flushing
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	0	2	2	1
Hypertension
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	2 / 18 (11.11%)	3 / 41 (7.32%)
occurrences all number	0	2	4	4
Hypotension
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	2	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 42 (2.38%)	3 / 24 (12.50%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	1	3	1	2
Pyrexia
subjects affected / exposed	5 / 42 (11.90%)	1 / 24 (4.17%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	7	1	0	0
Chest discomfort
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	2 / 18 (11.11%)	2 / 41 (4.88%)
occurrences all number	0	0	2	2
Chills
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Feeling abnormal
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Feeling hot
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Malaise
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Non-cardiac chest pain
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	2	0	0
Oedema peripheral
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Reproductive system and breast disorders
Amenorrhoea
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	3	1	1	1
Oropharyngeal pain
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	1 / 18 (5.56%)	3 / 41 (7.32%)
occurrences all number	1	2	1	4
Epistaxis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	0	0	1	2
Pharyngeal erythema
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Rhinorrhoea
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	0	2	1
Upper respiratory tract inflammation
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	2 / 18 (11.11%)	2 / 41 (4.88%)
occurrences all number	1	1	3	2
Depression
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	0	1	1
Insomnia
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	0	2	2	1
Panic disorder
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	3 / 42 (7.14%)	2 / 24 (8.33%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	4	3	1	1
Lymphocyte count decreased
subjects affected / exposed	2 / 42 (4.76%)	2 / 24 (8.33%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	2	2	1	1
Serum ferritin decreased
subjects affected / exposed	3 / 42 (7.14%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	3	1	1	2
Alanine aminotransferase increased
subjects affected / exposed	2 / 42 (4.76%)	2 / 24 (8.33%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	2	2	1	1
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Blood creatine phosphokinase increased
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	3	1	2	1
Blood fibrinogen decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	2 / 18 (11.11%)	0 / 41 (0.00%)
occurrences all number	0	0	2	0
Blood fibrinogen increased
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	1	1	1	0
Blood pressure increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Blood urine
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Complement factor decreased
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	2 / 18 (11.11%)	0 / 41 (0.00%)
occurrences all number	0	1	2	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	2	0	0
Low density lipoprotein increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	0	0	1	2
Neutrophil count decreased
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	2	0	2
Platelet count decreased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Protein urine present
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Prothrombin time prolonged
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Urobilinogen urine increased
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Weight decreased
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	1	1	1
Weight increased
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	1	1	1
White blood cell count decreased
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	2	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	2	1	1	0
Ligament sprain
subjects affected / exposed	1 / 42 (2.38%)	3 / 24 (12.50%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	3	0	1
Thermal burn
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	2	1	2	1
Arthropod sting
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Compression fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	0	0	1	2
Contusion
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Excoriation
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Joint injury
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	1	0	1	0
Lower limb fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Pelvic fracture
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Wound
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	2	2	2
Congenital, familial and genetic disorders
Left ventricle outflow tract obstruction
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Bradycardia
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	1	1	1
Palpitations
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	3	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 42 (2.38%)	3 / 24 (12.50%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	1	3	0	3
Headache
subjects affected / exposed	4 / 42 (9.52%)	4 / 24 (16.67%)	7 / 18 (38.89%)	10 / 41 (24.39%)
occurrences all number	6	5	11	28
Epilepsy
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Hypoaesthesia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Intercostal neuralgia
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	0	1	1
Muscle spasticity
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	1	1	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	5 / 42 (11.90%)	3 / 24 (12.50%)	5 / 18 (27.78%)	3 / 41 (7.32%)
occurrences all number	8	3	6	3
Iron deficiency anaemia
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	1	1	1	3
Leukopenia
subjects affected / exposed	4 / 42 (9.52%)	5 / 24 (20.83%)	3 / 18 (16.67%)	6 / 41 (14.63%)
occurrences all number	12	5	8	10
Lymphopenia
subjects affected / exposed	4 / 42 (9.52%)	1 / 24 (4.17%)	3 / 18 (16.67%)	3 / 41 (7.32%)
occurrences all number	9	1	9	7
Neutropenia
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	3	1	2	3
Hypofibrinogenaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Polycythaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	2 / 18 (11.11%)	2 / 41 (4.88%)
occurrences all number	1	1	5	2
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	0	4	2	1
Blepharitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Blepharospasm
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Cataract
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	1	1	1
Conjunctival deposit
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	2 / 18 (11.11%)	0 / 41 (0.00%)
occurrences all number	0	1	2	0
Dry eye
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	1	1	1
Eye pruritus
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Glaucoma
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Retinal haemorrhage
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 42 (2.38%)	3 / 24 (12.50%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	3	0	1
Constipation
subjects affected / exposed	7 / 42 (16.67%)	4 / 24 (16.67%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	8	7	2	2
Dental caries
subjects affected / exposed	2 / 42 (4.76%)	4 / 24 (16.67%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	2	5	1	2
Diarrhoea
subjects affected / exposed	3 / 42 (7.14%)	2 / 24 (8.33%)	3 / 18 (16.67%)	1 / 41 (2.44%)
occurrences all number	3	2	4	3
Gastritis
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	2 / 18 (11.11%)	4 / 41 (9.76%)
occurrences all number	0	2	2	4
Nausea
subjects affected / exposed	3 / 42 (7.14%)	1 / 24 (4.17%)	2 / 18 (11.11%)	3 / 41 (7.32%)
occurrences all number	3	1	2	3
Toothache
subjects affected / exposed	1 / 42 (2.38%)	4 / 24 (16.67%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	5	0	0
Abdominal distension
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Abdominal pain
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	2	0	2
Dyspepsia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Large intestine polyp
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Pancreatitis acute
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Plicated tongue
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	2	2	1	0
Hypertransaminasaemia
subjects affected / exposed	2 / 42 (4.76%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	2	0	2	2
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	1 / 42 (2.38%)	3 / 24 (12.50%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	1	3	0	2
Urticaria
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	2	0	3
Acne
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	1	1	1
Alopecia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	2 / 18 (11.11%)	1 / 41 (2.44%)
occurrences all number	0	0	2	1
Erythema
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	1	1	1
Rash
subjects affected / exposed	2 / 42 (4.76%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	2	1	3	0
Rash pruritic
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Renal and urinary disorders
Leukocyturia
subjects affected / exposed	3 / 42 (7.14%)	2 / 24 (8.33%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	3	3	0	2
Haematuria
subjects affected / exposed	2 / 42 (4.76%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	2	0	0
Nephrolithiasis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 42 (0.00%)	1 / 24 (4.17%)	1 / 18 (5.56%)	4 / 41 (9.76%)
occurrences all number	0	1	1	4
Back pain
subjects affected / exposed	5 / 42 (11.90%)	2 / 24 (8.33%)	3 / 18 (16.67%)	4 / 41 (9.76%)
occurrences all number	9	2	3	4
Myalgia
subjects affected / exposed	2 / 42 (4.76%)	3 / 24 (12.50%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	2	4	6	5
Pain in extremity
subjects affected / exposed	3 / 42 (7.14%)	0 / 24 (0.00%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences all number	3	0	0	1
Intervertebral disc protrusion
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Myopathy toxic
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	1	0	1	1
Neck pain
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Osteoarthritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Spinal osteoarthritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Spinal pain
subjects affected / exposed	1 / 42 (2.38%)	0 / 24 (0.00%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	1	0	1	2
Infections and infestations
Cystitis
subjects affected / exposed	4 / 42 (9.52%)	2 / 24 (8.33%)	4 / 18 (22.22%)	3 / 41 (7.32%)
occurrences all number	6	2	5	4
Herpes zoster
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	0 / 18 (0.00%)	2 / 41 (4.88%)
occurrences all number	1	2	0	2
Influenza
subjects affected / exposed	4 / 42 (9.52%)	2 / 24 (8.33%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	5	3	1	0
Nasopharyngitis
subjects affected / exposed	7 / 42 (16.67%)	10 / 24 (41.67%)	2 / 18 (11.11%)	10 / 41 (24.39%)
occurrences all number	13	35	5	22
Oral herpes
subjects affected / exposed	3 / 42 (7.14%)	2 / 24 (8.33%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	19	3	3	6
Pharyngitis
subjects affected / exposed	3 / 42 (7.14%)	0 / 24 (0.00%)	1 / 18 (5.56%)	4 / 41 (9.76%)
occurrences all number	10	0	1	6
Rhinitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	0 / 18 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	0	4
Sinusitis
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	1 / 18 (5.56%)	3 / 41 (7.32%)
occurrences all number	0	2	1	4
Upper respiratory tract infection
subjects affected / exposed	6 / 42 (14.29%)	6 / 24 (25.00%)	5 / 18 (27.78%)	10 / 41 (24.39%)
occurrences all number	11	7	18	26
Urinary tract infection
subjects affected / exposed	7 / 42 (16.67%)	7 / 24 (29.17%)	2 / 18 (11.11%)	6 / 41 (14.63%)
occurrences all number	7	11	11	8
Bacteriuria
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	1	1	1	0
Cellulitis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Hordeolum
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	2	0	0
Onychomycosis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Oral candidiasis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Otitis externa
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	2	0	0
Periodontitis
subjects affected / exposed	0 / 42 (0.00%)	2 / 24 (8.33%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	0	5	1	1
Pneumonia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Pyelonephritis
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Respiratory tract infection
subjects affected / exposed	1 / 42 (2.38%)	1 / 24 (4.17%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	2	3	1	0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 42 (4.76%)	0 / 24 (0.00%)	1 / 18 (5.56%)	1 / 41 (2.44%)
occurrences all number	2	0	1	1
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	1 / 42 (2.38%)	2 / 24 (8.33%)	0 / 18 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	2	0	1
Hypercholesterolaemia
subjects affected / exposed	5 / 42 (11.90%)	3 / 24 (12.50%)	1 / 18 (5.56%)	4 / 41 (9.76%)
occurrences all number	5	4	7	10
Hyperlipidaemia
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	2 / 18 (11.11%)	2 / 41 (4.88%)
occurrences all number	0	0	2	2
Dehydration
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Hyperglycaemia
subjects affected / exposed	2 / 42 (4.76%)	2 / 24 (8.33%)	0 / 18 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	2	0	0
Iron deficiency
subjects affected / exposed	0 / 42 (0.00%)	0 / 24 (0.00%)	1 / 18 (5.56%)	2 / 41 (4.88%)
occurrences all number	0	0	1	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

29 Nov 2013

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

27 Feb 2014

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

18 Dec 2014

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

03 Jun 2015

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

19 Oct 2015

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

14 Dec 2016

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

17 Apr 2017

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

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

Secondary: Relapse-Free Rate During the DB Period

Secondary: Relapse-Free Rate During the DB Period

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Serum Satralizumab Concentration During the DB Period

Secondary: Serum Satralizumab Concentration During the DB Period

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time

Secondary: Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time

Secondary: Percentage of Blood Plasmablast Over Time

Secondary: Percentage of Blood Plasmablast Over Time

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