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Clinical Trial Results:
Long-Term Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Tocilizumab in Patients with Polyarticular-Course and Systemic Juvenile Idiopathic Arthritis

Summary
EudraCT number	2013-005212-98
Trial protocol	DE IT GB ES FR
Global end of trial date	24 Nov 2021

Results information
Results version number	v1(current)
This version publication date	11 Jun 2022
First version publication date	11 Jun 2022
Other versions

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

WA29231

ISRCTN number

US NCT number

NCT02165345

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)

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

24 Nov 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Nov 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

This trial was an extension of Roche trials WA28117 and WA28118 and evaluated the long-term safety and efficacy of subcutaneous tocilizumab (SC TCZ) in pediatric participants with polyarticular-course and systemic juvenile idiopathic arthritis (pJIA and sJIA). Efficacy evaluation was performed for up to 3 years, and safety evaluation was done for up to 5 years.

Protection of trial subjects

All participants (or their parents or guardians) were required to sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Jul 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 6

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Brazil: 3

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

Germany: 14

Country: Number of subjects enrolled

Spain: 16

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Italy: 2

Country: Number of subjects enrolled

Mexico: 3

Country: Number of subjects enrolled

Russian Federation: 2

Country: Number of subjects enrolled

United States: 17

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Pediatric participants from related Roche studies with polyarticular-course and systemic juvenile idiopathic arthritis (pJIA and sJIA)

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

SC TCZ 162 mg Q3W (< 30 kg) pJIA

Arm description

Participants received SC TCZ according to body weight and JIA subtype.

Arm type

Experimental

Investigational medicinal product name

Subcutaneous tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

162 mg Q3W

SC TCZ 162 mg Q2W (>= 30 kg) pJIA

Arm description

Participants received SC TCZ according to body weight and JIA subtype.

Arm type

Experimental

Investigational medicinal product name

Subcutaneous tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

162 mg Q2W

SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA

Arm description

Participants received SC TCZ according to body weight and JIA subtype.

Arm type

Experimental

Investigational medicinal product name

Subcutaneous tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

162 mg Q10D or Q2W

SC TCZ 162 mg QW (>= 30 kg) sJIA

Arm description

Participants received SC TCZ according to body weight and JIA subtype.

Arm type

Experimental

Investigational medicinal product name

Subcutaneous tocilizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

162 mg QW

Number of subjects in period 1	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Started	24	20	19	19
Completed	13	6	1	5
Not completed	11	14	18	14
Consent withdrawn by subject	1	4	2	4
Physician decision	1	1	2	2
Adverse event, non-fatal	1	1	-	-
Commercial Drug Available	3	5	8	8
Pregnancy	-	1	-	-
Study Terminated by Sponsor	3	-	4	-
Lost to follow-up	-	-	1	-
Lack of efficacy	2	2	1	-

Baseline characteristics

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Reporting group title

SC TCZ 162 mg Q3W (< 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q2W (>= 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg QW (>= 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA	Total
Number of subjects	24	20	19	19	82
Age Categorical
Units: Subjects
Children (2-11 years)	24	3	19	4	50
Adolescents (12-17 years)	0	14	0	11	25
Adults (18-64 years)	0	3	0	4	7
Age Continuous
Units: years
arithmetic mean (standard deviation)	6.8 ( 2.1 )	14.7 ( 2.8 )	4.9 ( 2.3 )	13.9 ( 3.5 )	-
Gender Categorical
Units: Subjects
Female	18	14	10	11	53
Male	6	6	9	8	29
Race
Units: Subjects
American Indian or Alaska Native	0	0	1	0	1
Asian	0	0	0	1	1
Black or African American	0	0	1	0	1
White	20	19	16	16	71
Multiple	0	1	0	1	2
Unknown	4	0	1	1	6
Ethnicity
Units: Subjects
Hispanic or Latino	6	3	3	0	12
Not Hispanic or Latino	14	17	15	15	61
Not Stated	2	0	1	3	6
Unknown	2	0	0	1	3

End points

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Reporting group title

SC TCZ 162 mg Q3W (< 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q2W (>= 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg QW (>= 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Primary: Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA

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End point title

Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA ^[1] ^[2]

End point description

The JADAS 71 is a composite score derived from physician’s global assessment of disease activity VAS, patient/parent’s global assessment of overall well-being VAS, normalized ESR, and the number of joints with active arthritis (0 - 71). The score ranges from 0–101.

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[2] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Number of subjects analysed	24	20
Units: None
median (full range (min-max))
Baseline (n = 22; n = 20)	0.40 (0.0 to 18.4)	2.05 (0.0 to 27.6)
Week 12 (n = 21; n = 20)	0.20 (0.0 to 15.9)	0.85 (0.0 to 24.9)
Week 24 (n = 22; n = 19)	0.30 (0.0 to 16.3)	2.30 (0.0 to 11.6)
Week 36 (n = 22; n = 19)	0.00 (0.0 to 14.6)	1.90 (0.0 to 11.7)
Week 48 (n = 21; n = 19)	0.20 (0.0 to 14.6)	1.80 (0.0 to 12.0)
Week 60 (n = 21; n = 19)	0.40 (0.0 to 19.4)	2.20 (0.0 to 42.5)
Week 72 (n = 21; n = 17)	0.00 (0.0 to 8.2)	1.50 (0.0 to 7.7)
Week 84 (n = 20; n = 17)	0.05 (0.0 to 13.5)	2.00 (0.0 to 10.0)
Week 96 (n = 20; n = 17)	0.10 (0.0 to 15.4)	2.00 (0.0 to 4.4)
Week 108 (n = 19; n = 16)	0.30 (0.0 to 11.3)	2.15 (0.0 to 7.6)
Week 120 (n = 19; n =16)	0.20 (0.0 to 10.4)	1.40 (0.0 to 4.5)
Week 132 (n = 19; n = 16)	0.30 (0.0 to 11.5)	0.45 (0.0 to 10.5)
Week 144 (n = 19; n = 16)	0.30 (0.0 to 11.5)	1.05 (0.1 to 21.0)
Week 156 (n = 17; n = 15)	0.00 (0.0 to 3.1)	1.70 (0.0 to 21.0)

No statistical analyses for this end point

Primary: JADAS-71 - sJIA

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End point title

JADAS-71 - sJIA ^[3] ^[4]

End point description

The JADAS-71 is a composite score derived from physician's global assessment of disease activity VAS, patient/parent's global assessment of overall well-being VAS, normalized ESR, and the number of joints with active arthritis (0 - 71). The score ranges from 0 - 101.

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical tests were planned for this study

End point values	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Number of subjects analysed	19	19
Units: None
median (full range (min-max))
Baseline (n = 19; n = 18)	0.40 (0.0 to 14.2)	0.25 (0.0 to 11.2)
Week 8 (n = 19; n = 17)	0.50 (0.0 to 27.5)	0.20 (0.0 to 14.2)
Week 16 (n = 18; n = 18)	0.05 (0.0 to 3.5)	0.15 (0.0 to 5.8)
Week 24 (n = 17; n = 18)	0.40 (0.0 to 7.7)	0.35 (0.0 to 7.3)
Week 32 (n = 17; n = 18)	0.30 (0.0 to 14.1)	0.30 (0.0 to 5.6)
Week 40 (n = 17; n = 17)	0.40 (0.0 to 7.9)	0.10 (0.0 to 3.6)
Week 48 (n = 17; n = 16)	0.30 (0.0 to 2.6)	0.15 (0.0 to 7.3)
Week 56 (n = 17; n = 16)	0.00 (0.0 to 2.6)	0.10 (0.0 to 9.7)
Week 64 (n = 17; n = 16)	0.00 (0.0 to 12.2)	0.05 (0.0 to 6.1)
Week 72 (n = 17; n = 16)	0.10 (0.0 to 4.7)	0.15 (0.0 to 1.7)
Week 80 (n = 17; n = 16)	0.10 (0.0 to 3.2)	0.20 (0.0 to 6.2)
Week 88 (n = 17; n = 16)	0.00 (0.0 to 5.2)	0.40 (0.0 to 8.6)
Week 96 (n = 15; n = 16)	0.10 (0.0 to 8.3)	0.45 (0.0 to 3.8)
Week 104 (n = 13; n = 16)	0.00 (0.0 to 1.6)	0.15 (0.0 to 1.9)
Week 112 (n = 13; n = 15)	0.00 (0.0 to 1.4)	0.10 (0.0 to 2.4)
Week 120 (n = 12; n = 15)	0.05 (0.0 to 1.6)	0.10 (0.0 to 1.7)
Week 128 (n = 12; n = 14)	0.00 (0.0 to 12.8)	0.15 (0.0 to 2.1)
Week 136 (n = 12; n = 14)	0.10 (0.0 to 1.9)	0.20 (0.0 to 2.1)
Week 144 (n = 11; n = 14)	0.00 (0.0 to 10.9)	0.10 (0.0 to 1.6)
Week 152 (n = 11; n = 13)	0.00 (0.0 to 8.3)	0.10 (0.0 to 2.0)

No statistical analyses for this end point

Primary: Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI)

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End point title

Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI) ^[5]

End point description

Hypersensitivity is defined as any AEs occurring during or within 24 hours of TCZ treatment and not deemed unrelated to study medication by the investigator, excluding injection site reactions.

End point type

Primary

End point timeframe

Baseline up to 5 years

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study

End point values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Number of subjects analysed	24	20	19	19
Units: Percentage of participants
number (not applicable)
AEs	100.0	100.0	100.0	100.0
SAEs	12.5	15.0	15.8	10.5
AESI - hypersensitivity	12.5	0	5.3	5.3
AESI - serious infections and infestations	12.5	10.0	5.3	0
AESI - Anaphylactic reactions	0	0	0	0
AESI - anaphylactic reactions (Sampsons Criteria)	0	0	0	0
AESI - serious bleeding	0	0	0	0
AESI - demyelinating AEs	0	0	0	0
AESI - gastrointestinal perforations	0	0	0	0
AESI - serious hepatic adverse events	0	0	0	0
AESI - malignancies	0	0	0	0
AESI - myocardial infarctions	0	0	0	0
AESI - opportunistic infections	0	0	0	0
AESI - stroke (ischaemic or hemorrhagic)	0	0	0	0
AESI - suspected transmission of infectious agent	0	0	0	0

No statistical analyses for this end point

Primary: Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA

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End point title

Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA ^[6] ^[7]

End point description

Childhood health assessment questionnaire-disability index (CHAQ-DI) was recorded to evaluate functional ability at a scale of 0 (best) to 3 (worst).

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[7] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Number of subjects analysed	24	20
Units: None
median (full range (min-max))
Baseline (n = 24; n = 20)	0.0000 (0.0000 to 1.750)	0.000 (0.000 to 2.750)
Week 12 (n = 24; n = 20)	0.1250 (0.000 to 1.875)	0.1250 (0.000 to 2.250)
Week 24 (n = 24; n = 19)	0.0000 (0.000 to 1.875)	0.1250 (0.000 to 2.000)
Week 36 (n = 24; n = 19)	0.0000 (0.000 to 1.750)	0.0000 (0.000 to 2.000)
Week 48 (n = 23; n = 19)	0.0000 (0.000 to 1.750)	0.1250 (0.000 to 2.000)
Week 60 (n = 23; n = 19)	0.0000 (0.000 to 1.875)	0.0000 (0.000 to 2.000)
Week 72 (n = 23; n = 17)	0.0000 (0.000 to 1.875)	0.0000 (0.000 to 2.000)
Week 84 (n = 22; n = 17)	0.0000 (0.000 to 1.500)	0.0000 (0.000 to 2.000)
Week 96 (n = 22; n = 17)	0.0000 (0.000 to 1.750)	0.0000 (0.000 to 2.000)
Week 108 (n = 21; n = 16)	0.0000 (0.000 to 1.750)	0.0000 (0.000 to 2.000)
Week 120 (n = 21; n = 16)	0.0000 (0.000 to 1.875)	0.0000 (0.000 to 2.000)
Week 132 (n = 21; n = 16)	0.0000 (0.000 to 1.750)	0.0000 (0.000 to 2.000)
Week 144 (n = 20; n = 16)	0.0000 (0.000 to 1.375)	0.0000 (0.000 to 2.000)
Week 156 (n = 13; n = 12)	0.0000 (0.000 to 0.250)	0.0000 (0.000 to 0.125)

No statistical analyses for this end point

Primary: CHAQ-DI Score - sJIA

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End point title

CHAQ-DI Score - sJIA ^[8] ^[9]

End point description

Childhood health assessment questionnaire-disability index (CHAQ-DI) was recorded to evaluate functional ability at a scale of 0 (best) to 3 (worst).

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Number of subjects analysed	19	19
Units: None
median (full range (min-max))
Baseline (n = 19; n = 19)	0.0000 (0.000 to 0.500)	0.0000 (0.000 to 2.250)
Week 8 (n = 19; n = 18)	0.0000 (0.000 to 1.125)	0.0000 (0.000 to 1.750)
Week 16 (n = 18; n = 19)	0.0000 (0.000 to 0.625)	0.0000 (0.000 to 2.000)
Week 24 (n = 17; n = 19)	0.0000 (0.000 to 0.625)	0.0000 (0.000 to 2.000)
Week 32 (n = 17; n = 19)	0.0000 (0.000 to 0.500)	0.0000 (0.000 to 1.625)
Week 40 (n = 16; n = 18)	0.0000 (0.000 to 0.750)	0.0000 (0.000 to 2.000)
Week 48 (n = 16; n = 17)	0.0000 (0.000 to 0.625)	0.0000 (0.000 to 2.125)
Week 56 (n = 15; n = 17)	0.0000 (0.000 to 0.500)	0.0000 (0.000 to 2.125)
Week 64 (n = 16; n = 17)	0.0000 (0.000 to 0.500)	0.0000 (0.000 to 2.000)
Week 72 (n = 17; n = 17)	0.0000 (0.000 to 0.250)	0.0000 (0.000 to 1.875)
Week 80 (n = 17; n 17)	0.0000 (0.000 to 0.250)	0.0000 (0.000 to 1.750)
Week 88 (n = 16; n = 17)	0.0000 (0.000 to 0.375)	0.0000 (0.000 to 1.875)
Week 96 (n = 14; n = 17)	0.0000 (0.000 to 0.125)	0.0000 (0.000 to 1.750)
Week 104 (n = 13; n = 17)	0.0000 (0.000 to 0.625)	0.0000 (0.000 to 1.875)
Week 112 (n = 12; n = 16)	0.0000 (0.000 to 0.125)	0.0000 (0.000 to 2.125)
Week 120 (n = 11; n = 14)	0.0000 (0.000 to 0.250)	0.0000 (0.000 to 1.375)
Week 128 (n = 10; n = 14)	0.0000 (0.000 to 0.250)	0.0000 (0.000 to 2.000)
Week 136 (n = 11; n = 14)	0.0000 (0.000 to 0.125)	0.0000 (0.000 to 1.500)
Week 144 (n = 9; n = 14)	0.0000 (0.000 to 0.500)	0.0000 (0.000 to 1.375)
Week 152 (n = 6; n = 13)	0.1875 (0.000 to 0.625)	0.0000 (0.000 to 1.875)

No statistical analyses for this end point

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - pJIA

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End point title

Proportion of Participants with Protocol-Defined Inactive Disease - pJIA ^[10] ^[11]

End point description

Inactive disease was defined as follows: • No presence of active joints • Absence of active uveitis (defined by the AE preferred terms ‘uveitis’ and ‘intermediate uveitis’) • No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to pJIA • Normal ESR (< 20 mm/hr) • Physician global VAS </= 10 mm • Duration of morning stiffness </= 15 minutes

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[11] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Number of subjects analysed	24	20
Units: Percentage of participants
number (not applicable)
Baseline (n = 24; n = 20)	75.0	50.0
Week 12 (n = 24; n = 20)	79.2	60.0
Week 24 (n = 24; n = 19)	70.8	52.6
Week 36 (n = 24; n = 19)	75.0	57.9
Week 48 (n = 23; n = 19)	78.3	42.1
Week 60 (n = 23; n = 19)	82.6	42.1
Week 72 (n = 23; n = 17)	69.6	52.9
Week 84 (n = 22; n = 17)	77.3	52.9
Week 96 (n = 22; n = 17)	77.3	58.8
Week 108 (n = 21; n = 16)	90.5	50.0
Week 120 (n = 21; n = 16)	81.0	43.8
Week 132 (n = 21; n = 16)	81.0	81.3
Week 144 (n = 21; n = 16)	81.0	56.3
Week 156 (n= 19; n = 15)	89.5	53.3

No statistical analyses for this end point

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - sJIA

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End point title

Proportion of Participants with Protocol-Defined Inactive Disease - sJIA ^[12] ^[13]

End point description

End point type

Primary

End point timeframe

Baseline up to 3 years

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[13] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Number of subjects analysed	19	19
Units: Percentage of participants
number (not applicable)
Baseline (n = 19; n = 19)	73.7	78.9
Week 8 (n = 19; n = 19)	78.9	78.9
Week 16 (n = 18; n = 19)	88.9	94.7
Week 24 (n = 17; n = 19)	70.6	89.5
Week 32 (n = 17; n = 19)	88.2	89.5
Week 40 (n = 17; n = 18)	76.5	88.9
Week 48 (n = 17; n = 17)	94.1	88.2
Week 56 (n = 17; n = 17)	88.2	82.4
Week 64 (n = 17; n = 17)	82.4	94.1
Week 72 (n = 17; n = 17)	82.4	88.2
Week 80 (n = 17; n = 17)	82.4	94.1
Week 88 (n = 17; n = 17)	82.4	94.1
Week 96 (n = 15; n = 17)	86.7	76.5
Week 104 (n = 13; n = 17)	84.6	82.4
Week 112 (n = 13; n = 16)	84.6	81.3
Week 120 (n = 12; n = 16)	83.3	87.5
Week 128 (n = 12; n = 14)	91.7	85.7
Week 136 (n = 12; n = 14)	83.3	85.7
Week 144 (n = 11; n = 14)	90.9	78.6
Week 152 (n = 11; n = 13)	90.9	92.3

No statistical analyses for this end point

Primary: Proportion of Participants with Clinical Remission - pJIA

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End point title

Proportion of Participants with Clinical Remission - pJIA ^[14] ^[15]

End point description

Clinical remission was defined as inactive disease for a minimum of 6 continuous months irrespective of disease-modifying anti-rheumatic drug, nonsteroidal anti inflammatory drug, or corticosteroid use.

End point type

Primary

End point timeframe

From Week 24 up to 3 years

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[15] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Number of subjects analysed	24	20
Units: Percentage of participants
number (not applicable)
Week 24 (n = 24; n = 19)	50.0	42.1
Week 36 (n = 24; n = 19)	58.3	36.8
Week 48 (n = 23; n = 19)	52.2	21.1
Week 60 (n = 23; n = 19)	60.9	21.1
Week 72 (n = 23; n = 17)	60.9	41.2
Week 84 (n = 22; n = 17)	63.6	35.3
Week 96 (n = 22; n = 17)	59.1	35.3
Week 108 (n = 21; n = 16)	66.7	31.3
Week 120 (n = 21; n = 16)	61.9	31.3
Week 132 (n = 21; n = 16)	66.7	31.3
Week 144 (n = 21; n = 16)	66.7	25.0
Week 156 (n = 19; n = 15)	73.7	33.3

No statistical analyses for this end point

Primary: Proportion of Participants with Clinical Remission - sJIA

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End point title

Proportion of Participants with Clinical Remission - sJIA ^[16] ^[17]

End point description

End point type

Primary

End point timeframe

From Week 24 up to 3 years

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical tests were planned for this study
[17] - 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: This end point is specific to the arm reported

End point values	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA
Number of subjects analysed	19	19
Units: Percentage of Participants
number (not applicable)
Week 24 (n = 17; n = 19)	70.6	68.4
Week 32 (n = 17; n= 19)	70.6	68.4
Week 40 (n = 17; n = 18)	70.6	77.8
Week 48 (n = 17; n = 17)	58.8	76.5
Week 56 (n = 17; n= 17)	76.5	76.5
Week 64 (n = 17;n= 17)	70.6	76.5
Week 72 (n = 17; n = 17)	76.5	76.5
Week 80 (n = 17; n = 17)	70.6	76.5
Week 88 (n = 17; n = 17)	70.6	88.2
Week 96 (n = 15; n = 17)	66.7	82.4
Week 104 (n = 13; n = 17)	76.9	76.5
Week 112 (n = 13; n = 16)	76.9	68.8
Week 120 (n = 12; n = 16)	83.3	62.5
Week 128 (n = 12; n = 14)	75.0	64.3
Week 136 (n = 12; n = 14)	75.0	71.4
Week 144 (n = 11; n = 14)	72.7	78.6
Week 152 (n = 11; n = 13)	81.8	76.9

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 5 years

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

SC TCZ 162 mg Q3W (< 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg QW (>= 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Reporting group title

SC TCZ 162 mg Q2W (>= 30 kg) pJIA

Reporting group description

Participants received SC TCZ according to body weight and JIA subtype.

Serious adverse events	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 24 (12.50%)	2 / 19 (10.53%)	3 / 19 (15.79%)	3 / 20 (15.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (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
Alanine aminotransferase increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (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
Injury, poisoning and procedural complications
Procedural complication
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (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
Craniocerebral injury
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
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
Eye disorders
Eye pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
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
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (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
Pneumonia mycoplasmal
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (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
Appendicitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
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
Furuncle
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (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
Varicella
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (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
Infectious mononucleosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
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

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

Non-serious adverse events	SC TCZ 162 mg Q3W (< 30 kg) pJIA	SC TCZ 162 mg QW (>= 30 kg) sJIA	SC TCZ 162 mg Q10D or Q2W (< 30 kg) sJIA	SC TCZ 162 mg Q2W (>= 30 kg) pJIA
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 24 (100.00%)	19 / 19 (100.00%)	19 / 19 (100.00%)	20 / 20 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	2 / 24 (8.33%)	3 / 19 (15.79%)	1 / 19 (5.26%)	2 / 20 (10.00%)
occurrences all number	2	3	1	3
Vascular disorders
Haematoma
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Surgical and medical procedures
Sinus operation
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Tooth extraction
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Peripheral swelling
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	2 / 20 (10.00%)
occurrences all number	0	0	1	2
Swelling
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Drug intolerance
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Injection site urticaria
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	15
Injection site pruritus
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	0	1
Injection site warmth
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Chest pain
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Fatigue
subjects affected / exposed	2 / 24 (8.33%)	3 / 19 (15.79%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	3	3	0	3
Injection site erythema
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	0 / 19 (0.00%)	4 / 20 (20.00%)
occurrences all number	2	2	0	38
Injection site bruising
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Mass
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Injection site swelling
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 19 (0.00%)	3 / 20 (15.00%)
occurrences all number	0	6	0	8
Asthenia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Injection site pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Pain
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	0	1
Illness
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Malaise
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Pyrexia
subjects affected / exposed	7 / 24 (29.17%)	3 / 19 (15.79%)	7 / 19 (36.84%)	3 / 20 (15.00%)
occurrences all number	14	5	9	3
Injection site reaction
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Injection site haematoma
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	4	0	1
Injection site induration
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Swelling face
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	2	1	0	2
Dust allergy
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Allergy to arthropod bite
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Drug hypersensitivity
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	3	0	0
Heavy menstrual bleeding
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Intermenstrual bleeding
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Vulvovaginal erythema
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Menstruation irregular
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	4	0	3	0
Epistaxis
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	2	1	2	1
Laryngeal inflammation
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Tonsillolith
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Dyspnoea
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0
Oropharyngeal pain
subjects affected / exposed	3 / 24 (12.50%)	5 / 19 (26.32%)	3 / 19 (15.79%)	6 / 20 (30.00%)
occurrences all number	5	13	3	8
Pharyngeal ulceration
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Rhinorrhoea
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	3	3	1	0
Rhinitis allergic
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Cough
subjects affected / exposed	10 / 24 (41.67%)	2 / 19 (10.53%)	7 / 19 (36.84%)	2 / 20 (10.00%)
occurrences all number	19	2	12	2
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Attention deficit hyperactivity disorder
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Mood swings
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Depression
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2
Anxiety
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Suicidal ideation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Learning disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Depressed mood
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Investigations
Neutrophil count decreased
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	3	1	4	0
Blood triglycerides increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Aspartate aminotransferase increased
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	1	1	1	1
Salivary gland scan abnormal
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Blood creatinine increased
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
White blood cell count decreased
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	1	0	2	0
Haematocrit decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
White blood cell count increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Body temperature increased
subjects affected / exposed	3 / 24 (12.50%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	0	0	0
Chlamydia test positive
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Hepatic enzyme increased
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	3	0	0	2
Platelet count decreased
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Alanine aminotransferase increased
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	2	0	1	1
Injury, poisoning and procedural complications
Skin injury
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Injury
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	1	0	1	1
Skin abrasion
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	3	0	0
Nail injury
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Thermal burn
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Wrist fracture
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0
Hand fracture
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Contusion
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	2	0	1
Induced abortion failed
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Joint injury
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
Muscle strain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Limb injury
subjects affected / exposed	4 / 24 (16.67%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	4	0	1	0
Arthropod bite
subjects affected / exposed	2 / 24 (8.33%)	3 / 19 (15.79%)	2 / 19 (10.53%)	2 / 20 (10.00%)
occurrences all number	2	4	2	2
Limb fracture
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Wound
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Ligament sprain
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	3	0	0
Traumatic haematoma
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Ear injury
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Skin laceration
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Scratch
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0
Fall
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	3 / 19 (15.79%)	0 / 20 (0.00%)
occurrences all number	3	1	3	0
Pelvic bone injury
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Arthropod sting
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Upper limb fracture
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	2	0	1	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	2	0	0	2
Headache
subjects affected / exposed	4 / 24 (16.67%)	3 / 19 (15.79%)	5 / 19 (26.32%)	5 / 20 (25.00%)
occurrences all number	6	10	5	14
Paraesthesia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Syncope
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	1	0	1
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	2	0	1
Leukopenia
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	3	5	2	0
Lymphopenia
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Monocytopenia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Lymphadenitis
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Increased tendency to bruise
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Neutropenia
subjects affected / exposed	6 / 24 (25.00%)	3 / 19 (15.79%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	23	7	2	1
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Tympanic membrane perforation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Ear pain
subjects affected / exposed	3 / 24 (12.50%)	2 / 19 (10.53%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	3	2	2	0
Vertigo
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	2	0	3
Eye disorders
Ulcerative keratitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Conjunctivitis allergic
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Myopia
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Photophobia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Toothache
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	1	1	1	0
Tongue ulceration
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Abdominal pain upper
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	1	1	2	6
Dental discomfort
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Nausea
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	4 / 20 (20.00%)
occurrences all number	1	1	2	14
Eructation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Oral pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Odynophagia
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	5	0	1
Gastritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Vomiting
subjects affected / exposed	10 / 24 (41.67%)	1 / 19 (5.26%)	6 / 19 (31.58%)	2 / 20 (10.00%)
occurrences all number	13	1	11	6
Dental caries
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	2	0	1	0
Abdominal pain
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	2	1	2	3
Diarrhoea
subjects affected / exposed	10 / 24 (41.67%)	3 / 19 (15.79%)	4 / 19 (21.05%)	3 / 20 (15.00%)
occurrences all number	15	3	6	3
Flatulence
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Mouth ulceration
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Chapped lips
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Salivary gland mucocoele
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Aphthous ulcer
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	2 / 19 (10.53%)	3 / 20 (15.00%)
occurrences all number	0	1	2	5
Constipation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Skin and subcutaneous tissue disorders
Papule
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Rash
subjects affected / exposed	4 / 24 (16.67%)	4 / 19 (21.05%)	4 / 19 (21.05%)	2 / 20 (10.00%)
occurrences all number	5	15	7	3
Pseudoporphyria
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Dermatitis allergic
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	2	0	1
Hyperhidrosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Urticaria
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	0	3	2	0
Acne
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Angioedema
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Eczema
subjects affected / exposed	2 / 24 (8.33%)	3 / 19 (15.79%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	2	3	2	1
Pruritus
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	2	0	1	0
Blister
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Renal and urinary disorders
Renal colic
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Plantar fasciitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Back pain
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	2 / 20 (10.00%)
occurrences all number	1	3	3	2
Kyphosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Musculoskeletal stiffness
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	3	0	0	1
Arthralgia
subjects affected / exposed	11 / 24 (45.83%)	5 / 19 (26.32%)	5 / 19 (26.32%)	5 / 20 (25.00%)
occurrences all number	21	9	13	18
Fibromyalgia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Lordosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Arthritis
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	3 / 20 (15.00%)
occurrences all number	1	1	3	4
Foot deformity
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Juvenile idiopathic arthritis
subjects affected / exposed	3 / 24 (12.50%)	0 / 19 (0.00%)	2 / 19 (10.53%)	4 / 20 (20.00%)
occurrences all number	3	0	2	4
Neck pain
subjects affected / exposed	1 / 24 (4.17%)	3 / 19 (15.79%)	3 / 19 (15.79%)	0 / 20 (0.00%)
occurrences all number	1	3	5	0
Spinal disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Still's disease
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	3 / 19 (15.79%)	0 / 20 (0.00%)
occurrences all number	0	1	3	0
Coccydynia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Torticollis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Musculoskeletal pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Osteochondrosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Pain in extremity
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	2 / 19 (10.53%)	3 / 20 (15.00%)
occurrences all number	3	3	3	5
Myalgia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Joint effusion
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	4	1	0	0
Costochondritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Polyarthritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2
Groin pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Joint swelling
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 19 (5.26%)	3 / 20 (15.00%)
occurrences all number	8	1	3	5
Osteoarthritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2
Infections and infestations
Erysipelas
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Pharyngotonsillitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Candida infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Rhinitis
subjects affected / exposed	1 / 24 (4.17%)	3 / 19 (15.79%)	2 / 19 (10.53%)	2 / 20 (10.00%)
occurrences all number	1	4	3	2
Gingivitis
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
Viral infection
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	1	2	2	0
Paronychia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Otitis media acute
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	2	0	2	0
Furuncle
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0
Varicella
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	4	1	1	1
Localised infection
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	1	1	2	0
Gastroenteritis viral
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Skin infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Cystitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	3	0	2
Pharyngitis bacterial
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	3	0	0	0
Lower respiratory tract infection
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Nasopharyngitis
subjects affected / exposed	10 / 24 (41.67%)	10 / 19 (52.63%)	5 / 19 (26.32%)	9 / 20 (45.00%)
occurrences all number	18	32	18	22
Enteritis infectious
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Vulvovaginitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Post procedural infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Viral rash
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Erythema infectiosum
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Pneumonia
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	2 / 19 (10.53%)	0 / 20 (0.00%)
occurrences all number	1	0	2	0
Gastroenteritis
subjects affected / exposed	11 / 24 (45.83%)	1 / 19 (5.26%)	2 / 19 (10.53%)	3 / 20 (15.00%)
occurrences all number	15	1	2	3
Upper respiratory tract infection
subjects affected / exposed	4 / 24 (16.67%)	4 / 19 (21.05%)	9 / 19 (47.37%)	2 / 20 (10.00%)
occurrences all number	4	11	20	3
Hand-foot-and-mouth disease
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	1	0	1	0
Conjunctivitis
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	2	0	2	1
Sinusitis
subjects affected / exposed	1 / 24 (4.17%)	4 / 19 (21.05%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	6	0	2
Tonsillitis
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 19 (5.26%)	5 / 20 (25.00%)
occurrences all number	1	2	2	5
Otitis media chronic
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Urinary tract infection
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	2 / 20 (10.00%)
occurrences all number	3	0	0	2
Infected cyst
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Pharyngitis streptococcal
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	2 / 20 (10.00%)
occurrences all number	1	0	2	2
Respiratory tract infection
subjects affected / exposed	4 / 24 (16.67%)	2 / 19 (10.53%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	4	3	0	1
Bronchitis
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 19 (10.53%)	1 / 20 (5.00%)
occurrences all number	1	1	3	2
Rhinovirus infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Ear infection
subjects affected / exposed	4 / 24 (16.67%)	2 / 19 (10.53%)	5 / 19 (26.32%)	0 / 20 (0.00%)
occurrences all number	8	2	10	0
Tooth abscess
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Vulvovaginal candidiasis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	5	0	1	1
Epstein-Barr virus infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0
Oral herpes
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	5	0	0
Molluscum contagiosum
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0
Herpangina
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Lice infestation
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 19 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Influenza
subjects affected / exposed	4 / 24 (16.67%)	2 / 19 (10.53%)	3 / 19 (15.79%)	1 / 20 (5.00%)
occurrences all number	4	10	5	1
Impetigo
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	3	2	1	1
Otitis media
subjects affected / exposed	3 / 24 (12.50%)	0 / 19 (0.00%)	3 / 19 (15.79%)	1 / 20 (5.00%)
occurrences all number	3	0	3	3
Pharyngitis
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 19 (0.00%)	3 / 20 (15.00%)
occurrences all number	2	0	0	4
Tooth infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Metabolism and nutrition disorders
Vitamin D deficiency
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 19 (5.26%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Hypoglycaemia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Hypercholesterolaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 19 (5.26%)	0 / 20 (0.00%)
occurrences all number	0	4	1	0
Iron deficiency
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 19 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

02 May 2014

Updates to post-trial access, reasons for discontinuation, and exclusion criteria

23 Nov 2015

Updates to dosing regimen and eligibility criteria

23 Jun 2017

Updates to treatment period and sample collection

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.

The study was terminated 1 year earlier than planned for operational reasons. At the time of termination, 7 patients were remaining, all within the final year of study participation. They were able to continue treatment following study termination.

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Clinical trials

Clinical Trial Results:
Long-Term Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Tocilizumab in Patients with Polyarticular-Course and Systemic Juvenile Idiopathic Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA

Primary: Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA

Primary: JADAS-71 - sJIA

Primary: JADAS-71 - sJIA

Primary: Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI)

Primary: Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI)

Primary: Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA

Primary: Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA

Primary: CHAQ-DI Score - sJIA

Primary: CHAQ-DI Score - sJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - pJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - pJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - sJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - sJIA

Primary: Proportion of Participants with Clinical Remission - pJIA

Primary: Proportion of Participants with Clinical Remission - pJIA

Primary: Proportion of Participants with Clinical Remission - sJIA

Primary: Proportion of Participants with Clinical Remission - sJIA

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Belgium
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Cyprus
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Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
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Outside EU/EEA

Clinical trials

Clinical Trial Results: Long-Term Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Tocilizumab in Patients with Polyarticular-Course and Systemic Juvenile Idiopathic Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA

Primary: Juvenile Arthritis Disease Activity Score (JADAS-71) - pJIA

Primary: JADAS-71 - sJIA

Primary: JADAS-71 - sJIA

Primary: Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI)

Primary: Percentage of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (AESI)

Primary: Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA

Primary: Childhood Health Assessment Questionnaire - Disability Index (CHAQ-DI) Score - pJIA

Primary: CHAQ-DI Score - sJIA

Primary: CHAQ-DI Score - sJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - pJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - pJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - sJIA

Primary: Proportion of Participants with Protocol-Defined Inactive Disease - sJIA

Primary: Proportion of Participants with Clinical Remission - pJIA

Primary: Proportion of Participants with Clinical Remission - pJIA

Primary: Proportion of Participants with Clinical Remission - sJIA

Primary: Proportion of Participants with Clinical Remission - sJIA

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Long-Term Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Tocilizumab in Patients with Polyarticular-Course and Systemic Juvenile Idiopathic Arthritis