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Clinical Trial Results:
A Phase 2 Multi-Center, Open-Label, Follow-Up Study to Assess The Long-Term Safety and Efficacy of CDP6038 Administered Subcutaneously to Subjects With Active Rheumatoid Arthritis Who completed Study RA0056

Summary
EudraCT number	2010-022224-77
Trial protocol	GB BE
Global end of trial date	05 Aug 2013

Results information
Results version number	v1(current)
This version publication date	23 Mar 2022
First version publication date	23 Mar 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

RA0057

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

UCB Biopharma SRL

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, 1070

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

11 Oct 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

01 May 2013

Global end of trial reached?

Yes

Global end of trial date

05 Aug 2013

Was the trial ended prematurely?

Yes

Main objective of the trial

To assess the long-term safety of CDP6038 dosed at 120 milligrams (mg) once every 2 weeks (q2w) while treating the signs and symptoms of active rheumatoid arthritis in participants who have previously failed TNFα blocker therapy.

Protection of trial subjects

During the conduct of the study all subjects were closely monitored.

Background therapy

Not applicable

Evidence for comparator

Actual start date of recruitment

07 Mar 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 183

Worldwide total number of subjects

190

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)

147

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The present study was an open-label extension to study RA0056 (NCT01242488). Subjects completing the 12-week treatment period of study RA0056 had the opportunity to participate in this study. First subject enrolled: 07 March 2011. Early termination: 05 Aug 2013.

Screening details

198 subjects completed the parent study RA0056 (NCT01242488); 190 subjects were enrolled in study RA0057. The study was a single treatment study and all subjects received CDP6038 (olokizumab) 120 mg sc q2w, however, some results are also presented according to the previously assigned treatment arms of the parent study RA0056.

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

RA0056 CDP6038 (Olokizumab) 120 mg q2w

Arm description

CDP6038 (olokizumab) 120 mg administered every 2 weeks (q2w) sc in Study RA0056, and maintained at same dose (i.e. 120 mg q2w sc) at start of study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 120 mg olokizumab q2w at prespecified time points.

RA0056 CDP6038 (Olokizumab) 120 mg q4w

Arm description

CDP6038 (olokizumab) 120 mg administered every 4 weeks (q4w) sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 120 mg olokizumab q4w at prespecified time points.

RA0056 CDP6038 (Olokizumab) 240 mg q2w

Arm description

CDP6038 (olokizumab) 240 mg administered q2w sc in study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 240 mg olokizumab q2w at prespecified time points.

RA0056 CDP6038 (Olokizumab) 240 mg q4w

Arm description

CDP6038 (olokizumab) 240 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 240 mg olokizumab q4w at prespecified time points.

RA0056 CDP6038 (Olokizumab) 60 mg q2w

Arm description

CDP6038 (olokizumab) 60 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 60 mg olokizumab q2w at prespecified time points.

RA0056 CDP6038 (Olokizumab) 60 mg q4w

Arm description

CDP6038 (olokizumab) 60 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 60 mg olokizumab q4w at prespecified time points.

RA0056 Placebo

Arm description

Placebo (sodium chloride, 0.9%) was administered q2w or q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Placebo

Investigational medicinal product name

Olokizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received placebo matched to olokizumab at prespecified time points.

RA0056 Tocilizumab 8 mg/kg q4w

Arm description

Tocilizumab 8 mg/kg administered q4w iv in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Arm type

Experimental

Investigational medicinal product name

Tocilizumab

Investigational medicinal product code

CDP6038

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received 8 mg tocilizumab q4w at prespecified time points.

Number of subjects in period 1	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Started	20	20	21	20	17	16	40	36
Completed	4	12	8	7	7	5	9	15
Not completed	16	8	13	13	10	11	31	21
Patient decision due to transport	-	-	-	-	-	-	-	1
Methotrexate discontinued	-	-	-	1	-	-	-	-
Failure to comply with visits	-	-	-	-	-	-	-	1
Required restricted steroid injections	-	-	-	-	-	-	1	-
Investigator discretion	-	-	-	-	-	-	1	-
Consent withdrawn by subject	4	2	2	1	1	1	2	1
Ongoing missed appointments	-	-	-	-	-	-	1	-
Adverse event, non-fatal	3	1	4	3	1	6	11	3
Study termination	8	1	5	4	4	4	8	10
Continued elevated liver enzymes	-	-	-	1	-	-	-	-
Unspecified	-	-	-	-	-	-	1	-
Lost to follow-up	-	-	1	1	2	-	4	2
Lack of efficacy	1	4	1	1	1	-	2	3
Protocol deviation	-	-	-	1	1	-	-	-

Baseline characteristics

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Reporting group title

RA0056 CDP6038 (Olokizumab) 120 mg q2w

Reporting group description

CDP6038 (olokizumab) 120 mg administered every 2 weeks (q2w) sc in Study RA0056, and maintained at same dose (i.e. 120 mg q2w sc) at start of study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 120 mg q4w

Reporting group description

CDP6038 (olokizumab) 120 mg administered every 4 weeks (q4w) sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 240 mg q2w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q2w sc in study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 240 mg q4w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 60 mg q2w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 60 mg q4w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Placebo

Reporting group description

Placebo (sodium chloride, 0.9%) was administered q2w or q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Tocilizumab 8 mg/kg q4w

Reporting group description

Tocilizumab 8 mg/kg administered q4w iv in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	Total
Number of subjects	20	20	21	20	17	16	40	36	190
Age Categorical
Units: participants
<=18 years	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	17	16	17	14	13	14	27	29	147
>=65 years	3	4	4	6	4	2	13	7	43
Age continuous
Units: years
arithmetic mean (standard deviation)	53.8 ( 10.99 )	54.5 ( 11.9 )	56.1 ( 12.3 )	55.0 ( 12.7 )	57.9 ( 10.0 )	54.0 ( 12.1 )	58.9 ( 12.5 )	36.8 ( 10.3 )	-
Gender, Male/Female
Units: participants
Female	17	17	19	16	14	14	33	31	161
Male	3	3	2	4	3	2	7	5	29

End points

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Reporting group title

RA0056 CDP6038 (Olokizumab) 120 mg q2w

Reporting group description

CDP6038 (olokizumab) 120 mg administered every 2 weeks (q2w) sc in Study RA0056, and maintained at same dose (i.e. 120 mg q2w sc) at start of study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 120 mg q4w

Reporting group description

CDP6038 (olokizumab) 120 mg administered every 4 weeks (q4w) sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 240 mg q2w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q2w sc in study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 240 mg q4w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 60 mg q2w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (Olokizumab) 60 mg q4w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Placebo

Reporting group description

Placebo (sodium chloride, 0.9%) was administered q2w or q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Tocilizumab 8 mg/kg q4w

Reporting group description

Tocilizumab 8 mg/kg administered q4w iv in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Subject analysis set title

RA0056 CDP6038 (olokizumab) Combined

Subject analysis set type

Full analysis

Subject analysis set description

All doses of CDP6038 (olokizumab) (60 mg, 120 mg and 240 mg in Study RA0056) were pooled together as one combined treatment group. All subjects switched to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056).

Primary: Number of subjects with treatment-emergent adverse events (TEAEs)

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End point title

Number of subjects with treatment-emergent adverse events (TEAEs) ^[1]

End point description

Reported TEAEs included adverse events that started or worsened after the first dose of CDP6038 (olokizumab) in Study RA0057 and within 30 days after the last dose. Safety Population included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) in Study RA0057.

End point type

Primary

End point timeframe

From Baseline (Week 0 of Study RA0057) until 30 days after the last dose (maximum up to 780 days)

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: Only descriptive analyses was planned to be reported for this endpoint.

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: participants	17	20	19	18	15	15	39	35

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint count (C-reactive protein) (DAS28[CRP]) to Week 12 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint count (C-reactive protein) (DAS28[CRP]) to Week 12 of Study RA0057

End point description

DAS28(CRP) was calculated using tender/painful joint count (TJC) and swollen joint count (SJC) from 28 joints, Patient’s Global Assessment of Disease Activity (PtGADA)-Visual Analog Scale (VAS) and CRP using formula:DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 100mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP calculated in mg/L. The 28 joints: shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), proximal interphalangeal (PIP) joints of hands; and knees. Scores on DAS28(CRP): 0 to 10 (higher scores = more disease activity). A negative change in score= an improvement in disease activity. Full analysis set: all enrolled subjects who received at least 1 dose of CDP6038 and had at least 1 efficacy assessment in RA0057. Number of Participants Analyzed =participants evaluable for this assessment.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	13	17	19	15	15	15	32	29	94
Units: units on a scale
arithmetic mean (standard deviation)	-2.2809 ( 1.45737 )	-2.2485 ( 1.39384 )	-2.5123 ( 1.39667 )	-2.2230 ( 1.17572 )	-1.6957 ( 0.67335 )	-2.1735 ( 1.56606 )	-2.3727 ( 1.41421 )	-2.4710 ( 1.43947 )	-2.2020 ( 1.30149 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, PtGADA-VAS and CRP according to formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and PIP joints of hands; and knees. Scores on DAS28(CRP) range from 0 to approximately 10, where higher scores =more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 and had at least 1 efficacy measurement in RA0057. When baseline and actual mean scores were not available, change from baseline was not calculated. Number of Participants analyzed (N)=participants who were evaluable for assessment.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	13	14	19	10	13	14	31	29	83
Units: units on a scale
arithmetic mean (standard deviation)	-2.6441 ( 1.46566 )	1.46566 ( 1.17637 )	-2.5811 ( 1.40191 )	-2.5999 ( 1.16812 )	-1.7189 ( 0.87218 )	-2.4221 ( 1.37341 )	-2.1484 ( 1.34676 )	-2.7624 ( 1.47841 )	-2.4624 ( 1.28049 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, PtGADA-VAS and CRP according to formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and PIP joints of hands; and knees. Scores on DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057. When baseline and actual mean scores were not available, change from baseline was not calculated. N =participants who were evaluable for assessment.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	10	12	13	10	12	10	20	22	67
Units: units on a scale
arithmetic mean (standard deviation)	-2.3257 ( 1.07427 )	-2.2498 ( 1.66580 )	-2.5277 ( 1.56763 )	-2.7050 ( 0.96160 )	-2.3824 ( 0.79065 )	-2.1501 ( 0.64141 )	-2.2403 ( 1.47765 )	-2.7611 ( 1.31329 )	-2.3919 ( 1.17675 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, PtGADA-VAS and CRP according to formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and PIP joints of hands; and knees. Scores on DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change in DAS28(CRP) score indicates an improvement in disease activity. Analysis population was FAS. When baseline and actual mean scores were not available, change from baseline was not calculated. Here, N signifies participants who were evaluable for assessment. 99999 signifies that standard deviation (S.D.) could not be calculated as there was only 1 evaluable participant.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	3	1	3	2	3	2	2	5	14
Units: units on a scale
arithmetic mean (standard deviation)	-3.2427 ( 1.74642 )	-3.5767 ( 99999 )	-2.5985 ( 2.16200 )	-3.0999 ( 0.02877 )	-1.7516 ( 2.03992 )	-2.6451 ( 0.96108 )	-3.3173 ( 3.23508 )	-3.7982 ( 1.23889 )	-2.7032 ( 1.50391 )

No statistical analyses for this end point

Secondary: The American College of Rheumatology (ACR) 20% (ACR20) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

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End point title

The American College of Rheumatology (ACR) 20% (ACR20) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

End point description

ACR20 =at least 20% improvement from Baseline for each of TJC (68 joints)+ SJC (66 joints)+ at least 3 components of 5 for:PtGADA-VAS, Physician’s Global Assessment of Disease Activity (PhGADA)-VAS, Patient’s Assessment of Arthritis Pain (PAAP)-VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI) and CRP. Assessments: •TJC and SJC: same 2-point scale (0=absent;1=present).•PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms).•PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). •PAAP: 100 mm VAS (0=no pain;100=most severe pain). •HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. •CRP in mg/L. Missing values were considered as non-responding status. Analysis population was FAS.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	40.0	50.0	76.2	35.0	58.8	50.0	47.5	52.8	51.8

No statistical analyses for this end point

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

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End point title

The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

End point description

ACR20 represents at least 20% improvement from Baseline for each of TJC (68 joints)+ SJC (66 joints)+ at least 3 components of 5 for:PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: •TJC and SJC: same 2-point scale (0=absent;1=present). •PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). •PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). •PAAP: 100 mm VAS (0=no pain;100=most severe pain). •HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. •CRP in mg/L. Missing values were considered as non-responding status. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	40.0	50.0	66.7	30.0	47.1	62.5	42.5	63.9	49.1

No statistical analyses for this end point

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

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End point title

The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	40.0	30.0	42.9	35.0	47.1	43.8	25.0	50.0	39.5

No statistical analyses for this end point

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

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End point title

The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	15.0	5.0	9.5	5.0	11.8	12.5	2.5	13.9	9.6

No statistical analyses for this end point

Secondary: The ACR 50% (ACR50) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

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End point title

The ACR 50% (ACR50) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

End point description

ACR50 represents at least 50% improvement from Baseline for each of TJC (68 joints)+ SJC (66 joints)+ at least 3 components of 5 for:PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: •TJC and SJC: same 2-point scale (0=absent;1=present). •PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). •PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). •PAAP: 100 mm VAS (0=no pain;100=most severe pain). •HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. •CRP in mg/L. Missing values were considered as non-responding status. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	25.0	15.0	33.3	15.0	17.6	18.8	27.5	38.9	21.1

No statistical analyses for this end point

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

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End point title

The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	20.0	20.0	33.3	15.0	11.8	43.8	25.0	41.7	23.7

No statistical analyses for this end point

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

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End point title

The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	10.0	15.0	28.6	20.0	35.3	31.3	15.0	33.3	22.8

No statistical analyses for this end point

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

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End point title

The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	10.0	5.0	4.8	0.0	11.8	6.3	2.5	8.3	6.1

No statistical analyses for this end point

Secondary: The ACR 70% (ACR70) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

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End point title

The ACR 70% (ACR70) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

End point description

ACR70 represents at least 70% improvement from Baseline for each of TJC (68 joints)+ SJC (66 joints)+ at least 3 components of 5 for:PtGADA-VAS, PhGADA-VAS, PAAP-VAS, HAQ-DI and CRP. Assessments: •TJC and SJC: same 2-point scale (0=absent;1=present). •PtGADA: 100 mm VAS (0=very good, no symptoms;100=very poor, severe symptoms). •PhGADA: 100 mm VAS (0=very good, asymptomatic, no limitation of normal activities;100=very poor, very severe symptoms which were intolerable, inability to carry out all normal activities). •PAAP: 100 mm VAS (0=no pain;100=most severe pain). •HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, with lower scores indicates less disability. •CRP in mg/L. Missing values were considered as non-responding status. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	10.0	5.0	19.0	5.0	0.0	18.8	15.0	13.9	9.6

No statistical analyses for this end point

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

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End point title

The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	10.0	15.0	19.0	5.0	0.0	12.5	10.0	25.0	10.5

No statistical analyses for this end point

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

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End point title

The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	5.0	5.0	23.8	10.0	11.8	6.3	10.0	13.9	10.5

No statistical analyses for this end point

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

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End point title

The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) up to Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	20	20	21	20	17	16	40	36	114
Units: Percentage of responders
number (not applicable)	5.0	0.0	4.8	0.0	5.9	0.0	2.5	5.6	2.6

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 12 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) <2.6 at Week 12 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than 2.6 implies remission. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	25.0	30.0	38.1	25.0	0	18.8	25.0	25.0

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 24 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) <2.6 at Week 24 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	25.0	35.0	33.3	25.0	17.6	12.5	20.0	33.3

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 48 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) <2.6 at Week 48 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	20.0	30.0	23.8	20.0	29.4	12.5	15.0	22.2

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 96 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) <2.6 at Week 96 of Study RA0057

End point description

End point type

Secondary

End point timeframe

Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	10.0	5.0	9.5	5.0	11.8	0	2.5	8.3

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 12 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) ≤3.2 at Week 12 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score less than or equal to (<=) 3.2 implies low disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Week 12 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	35.6	40.0	52.4	30.0	17.6	25.0	35.0	44.4

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 24 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) ≤3.2 at Week 24 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score <=3.2 implies low disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Week 24 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	35.0	40.0	38.1	30.0	23.5	37.5	35.0	50.0

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 48 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) ≤3.2 at Week 48 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score <=3.2 implies low disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	25.0	45.0	23.8	25.0	29.4	18.8	22.5	47.2

No statistical analyses for this end point

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 96 of Study RA0057

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End point title

Percentage of subjects with DAS28(CRP) ≤3.2 at Week 96 of Study RA0057

End point description

DAS28(CRP) was calculated using the TJC and SJC from 28 joints, the PtGADA-VAS, and CRP according to the formula: DAS28(CRP)=0.56 * (TJC)^1/2 + 0.28 * (SJC)^1/2 + 0.36 * ln(CRP[mg/L]+1) + 0.014 * PtGADA + 0.96 Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 100 mm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • CRP value calculated in mg/L. The 28 joints included the shoulders, elbows, wrists; metacarpophalangeal (MCP), thumb interphalangeal (IP), and proximal interphalangeal (PIP) joints of the hands; and the knees. Scores on the DAS28(CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28(CRP) score <=3.2 implies low disease activity. FAS included all enrolled subjects who received at least 1 injection of CDP6038 (olokizumab) and in addition had at least 1 efficacy measurement in Study RA0057.

End point type

Secondary

End point timeframe

Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Number of subjects analysed	20	20	21	20	17	16	40	36
Units: Percentage of subjects
number (not applicable)	15.0	5.0	9.5	5.0	11.8	0	2.5	11.1

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057

End point description

CDAI was calculated using the TJC (28 joints), SJC (28 joints), PtGADA-VAS and PhGADA-VAS, according to following formula: SJC + TJC + PtGADA + PhGADA Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). The 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and proximal PIP joints of hands; and knees. Total score range is from 0-100, with the high scores representing high disease activity. A negative change in CDAI score indicates an improvement in disease activity. Analysis population was FAS. When baseline and actual mean scores were not available, change from baseline was not calculated. Number of participants analyzed =participants who were evaluable for assessment.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	10	13	14	10	12	10	20	23	69
Units: units on a scale
arithmetic mean (standard deviation)	-80.1000 ( 53.28425 )	-65.3373 ( 63.72098 )	-94.3335 ( 61.48562 )	-80.8077 ( 57.91606 )	-79.9231 ( 30.09849 )	-84.8378 ( 33.77586 )	-74.3315 ( 53.99274 )	-83.4950 ( 42.48396 )	-80.9650 ( 51.40554 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057

End point description

CDAI was calculated using TJC (28 joints), SJC (28 joints), PtGADA-VAS and PhGADA-VAS, as per formula: SJC + TJC + PtGADA + PhGADA Assessments: • TJC and SJC: assessed on same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and proximal PIP joints of hands; and knees. Total score range is from 0-100, high scores=high disease activity. A negative change in CDAI score indicates an improvement in disease activity. Analysis population was FAS. When baseline and actual mean scores were not available, change from baseline was not calculated. N=participants who were evaluable for assessment. 99999=S.D. could not be calculated as there was only 1 evaluable participant.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	3	1	3	2	3	2	2	5	14
Units: units on a scale
arithmetic mean (standard deviation)	-108.0000 ( 66.77574 )	-118.0000 ( 99999 )	-89.0000 ( 55.97321 )	-74.3846 ( 4.78657 )	-74.0000 ( 55.74944 )	-90.5000 ( 13.43503 )	-104.5000 ( 126.57211 )	-107.4000 ( 51.52960 )	-90.0550 ( 3.51706 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057

End point description

SDAI =TJC (28 joints), SJC (28 joints), PtGADA-VAS, PhGADA-VAS and CRP (in milligrams per decilitre [mg/dL]), as per the formula: SJC + TJC + PtGADA + PhGADA + CRP (mg/dL) Assessments: • TJC and SJC: assessed on the same 2-point scale (0=absent; 1=present). • PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities). • CRP range was from 0 to 10 mg/dL. 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and proximal PIP joints of hands; and knees. SDAI score ranges from 0 to 86, higher scores=worse disease. A negative change in SDAI score indicates an improvement in disease activity. Analysis population was FAS. When baseline and actual mean scores were not available, change from baseline was not calculated. N=participants who were evaluable for the assessment.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 48 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	10	13	13	10	12	10	20	23	68
Units: units on a scale
arithmetic mean (standard deviation)	-92.1000 ( 62.22799 )	-75.8757 ( 74.37825 )	-104.6668 ( 80.47988 )	-92.4077 ( 55.42723 )	-87.7564 ( 28.41084 )	-112.5378 ( 52.99896 )	-87.5815 ( 59.26016 )	-107.4080 ( 60.17362 )	-93.6851 ( 61.14304 )

No statistical analyses for this end point

Secondary: Change from Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057

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End point title

Change from Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057

End point description

SDAI was calculated using TJC (28 joints),SJC (28 joints), PtGADA-VAS, PhGADA-VAS and CRP (mg/dL), as per formula: SJC + TJC + PtGADA + PhGADA + CRP (mg/dL) Assessments:• TJC and SJC: assessed on same 2-point scale (0=absent; 1=present).• PtGADA: 10 cm VAS (0=very good, no symptoms; 100=very poor, severe symptoms). • PhGADA: 10 cm VAS (0=very good, asymptomatic and no limitation of normal activities; 100=very poor, very severe symptoms which were intolerable and inability to carry out all normal activities).• CRP range=0 to 10 mg/dL. 28 joints included shoulders, elbows, wrists; MCP, thumb IP, and proximal PIP joints of hands; and knees. SDAI score range=0 to 86, higher scores=worse disease. A negative change in SDAI score=improvement in disease activity. Analysis population was FAS. When baseline and actual mean scores were not available, change from baseline was not calculated. N=participants evaluable for assessment. 99999=S.D. was not calculated due to 1 evaluable participant.

End point type

Secondary

End point timeframe

Baseline (Week 0 of Study RA0056) and Week 96 (Study RA0057)

End point values	RA0056 CDP6038 (Olokizumab) 120 mg q2w	RA0056 CDP6038 (Olokizumab) 120 mg q4w	RA0056 CDP6038 (Olokizumab) 240 mg q2w	RA0056 CDP6038 (Olokizumab) 240 mg q4w	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (Olokizumab) 60 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w	RA0056 CDP6038 (olokizumab) Combined
Number of subjects analysed	3	1	3	2	3	2	2	5	14
Units: units on a scale
arithmetic mean (standard deviation)	-111.0000 ( 68.78953 )	-125.0000 ( 99999 )	-90.3333 ( 56.04760 )	-91.8846 ( 29.53531 )	-75.3333 ( 56.09219 )	-147.5000 ( 77.07464 )	-128.0000 ( 147.07821 )	-143.4000 ( 80.28574 )	-102.4121 ( 52.99390 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline (Week 0 of Study RA0057) until 30 days after the last dose (maximum up to 780 days)

Adverse event reporting additional description

Reported TEAEs included adverse events that started or worsened after the first dose of CDP6038 (olokizumab) in Study RA0057 and within 30 days after the last dose.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

RA0056 CDP6038 (Olokizumab) 60 mg q2w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (olokizumab) 60 mg q4w

Reporting group description

CDP6038 (olokizumab) 60 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (olokizumab) 120 mg q2w

Reporting group description

CDP6038 (olokizumab) 120 mg administered q2w sc in Study RA0056, and maintained at same dose (i.e. 120 mg q2w sc) at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (olokizumab) 120 mg q4w

Reporting group description

CDP6038 (olokizumab) 120 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 CDP6038 (olokizumab) 240 mg q2w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q2w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056).

Reporting group title

RA0056 CDP6038 (olokizumab) 240 mg q4w

Reporting group description

CDP6038 (olokizumab) 240 mg administered q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Placebo

Reporting group description

Placebo (sodium chloride, 0.9%) was administered q2w or q4w sc in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Reporting group title

RA0056 Tocilizumab 8 mg/kg q4w

Reporting group description

Tocilizumab 8 mg/kg administered q4w iv in Study RA0056, followed by switch to CDP6038 (olokizumab) 120 mg q2w sc at start of Study RA0057 (Week 12 of RA0056) for 48 weeks.

Serious adverse events	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (olokizumab) 60 mg q4w	RA0056 CDP6038 (olokizumab) 120 mg q2w	RA0056 CDP6038 (olokizumab) 120 mg q4w	RA0056 CDP6038 (olokizumab) 240 mg q2w	RA0056 CDP6038 (olokizumab) 240 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 17 (29.41%)	3 / 16 (18.75%)	3 / 20 (15.00%)	6 / 20 (30.00%)	6 / 21 (28.57%)	7 / 20 (35.00%)	14 / 40 (35.00%)	4 / 36 (11.11%)
number of deaths (all causes)	0	1	0	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0	0	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
B-cell lymphoma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basosquamous carcinoma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral artery occlusion
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Cholecystectomy
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fusion surgery
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Unevaluable event
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary infarction
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Emphysema
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngospasm
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression suicidal
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety disorder
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Rib fracture
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Transient ischaemic attack
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric perforation
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gangrene
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incision site cellulitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Furuncle
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Necrotising fasciitis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Sepsis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0

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

Non-serious adverse events	RA0056 CDP6038 (Olokizumab) 60 mg q2w	RA0056 CDP6038 (olokizumab) 60 mg q4w	RA0056 CDP6038 (olokizumab) 120 mg q2w	RA0056 CDP6038 (olokizumab) 120 mg q4w	RA0056 CDP6038 (olokizumab) 240 mg q2w	RA0056 CDP6038 (olokizumab) 240 mg q4w	RA0056 Placebo	RA0056 Tocilizumab 8 mg/kg q4w
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 17 (88.24%)	15 / 16 (93.75%)	16 / 20 (80.00%)	20 / 20 (100.00%)	18 / 21 (85.71%)	17 / 20 (85.00%)	36 / 40 (90.00%)	35 / 36 (97.22%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	3 / 20 (15.00%)	1 / 20 (5.00%)	3 / 21 (14.29%)	0 / 20 (0.00%)	2 / 40 (5.00%)	5 / 36 (13.89%)
occurrences all number	0	2	4	1	3	0	2	5
Deep vein thrombosis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	4 / 40 (10.00%)	2 / 36 (5.56%)
occurrences all number	0	2	1	0	0	1	4	2
Injection site reaction
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	2 / 20 (10.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	6 / 40 (15.00%)	8 / 36 (22.22%)
occurrences all number	2	0	2	3	0	1	8	14
Oedema peripheral
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)	3 / 40 (7.50%)	2 / 36 (5.56%)
occurrences all number	1	0	2	0	3	1	3	3
Injection site erythema
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	2 / 36 (5.56%)
occurrences all number	9	2	0	1	0	0	4	2
Injection site bruising
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	1	0	0	0	1	0	2
Injection site pain
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	3 / 40 (7.50%)	3 / 36 (8.33%)
occurrences all number	1	16	0	0	0	11	18	21
Injection site induration
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Injection site rash
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	0	0	0	0	1
Vessel puncture site haematoma
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Injection site swelling
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	2	0	0	0	0	0	1
Pyrexia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	1	2
Pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	0	2
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	2 / 20 (10.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	0	1	0	2	2	2	2	1
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	0	0	3	0	2	2	0
Nasal congestion
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	0	0	2	1	0	1	2	1
Respiratory tract congestion
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	3	0	1	1	1	3
Wheezing
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0
Cough
subjects affected / exposed	1 / 17 (5.88%)	4 / 16 (25.00%)	0 / 20 (0.00%)	4 / 20 (20.00%)	3 / 21 (14.29%)	2 / 20 (10.00%)	6 / 40 (15.00%)	5 / 36 (13.89%)
occurrences all number	1	6	0	6	3	2	7	8
Rhinorrhoea
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0
Haemoptysis
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 17 (5.88%)	3 / 16 (18.75%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 40 (2.50%)	1 / 36 (2.78%)
occurrences all number	1	3	0	0	0	2	1	1
Sinus congestion
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	3 / 36 (8.33%)
occurrences all number	0	0	0	0	0	1	0	3
Laryngeal mass
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	4 / 40 (10.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	0	1	0	4	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	1	1	0	5	1
Aspartate aminotransferase increased
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	2	0	0	1	1	0	5	1
Blood pressure increased
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	3	1	0	2	0	1	8
Lipids increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Blood cholesterol increased
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	1	1	0	2	0	1	1	0
Liver function test abnormal
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	3 / 40 (7.50%)	1 / 36 (2.78%)
occurrences all number	0	0	0	1	1	1	3	1
Platelet count decreased
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	1	0	0	4	2
Low density lipoprotein increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Blood pressure diastolic increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Blood pressure systolic increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	3 / 40 (7.50%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	5	0
Blood triglycerides increased
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	1 / 36 (2.78%)
occurrences all number	0	1	0	0	0	0	1	1
Haematocrit decreased
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	2	0	0	0	0	2	0
Haemoglobin decreased
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	3	0
Mammogram abnormal
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Red cell distribution width increased
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	3 / 20 (15.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	3	0	0	2	2
Contusion
subjects affected / exposed	2 / 17 (11.76%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	2 / 40 (5.00%)	0 / 36 (0.00%)
occurrences all number	4	1	0	1	0	1	3	0
Limb injury
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	1	0	1	1	0	0	0
Muscle strain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	1	0	0	1	3
Excoriation
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	2 / 36 (5.56%)
occurrences all number	1	0	0	0	1	0	2	4
Fall
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	2 / 20 (10.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	2	0	0	0	1	5	0	1
Wound
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0
Cartilage injury
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Ligament sprain
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Upper limb fracture
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Meniscus injury
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	6 / 20 (30.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	1 / 40 (2.50%)	4 / 36 (11.11%)
occurrences all number	2	0	5	7	2	1	1	8
Carpal tunnel syndrome
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	0	0	0	2	0	2	0
Sciatica
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 40 (2.50%)	1 / 36 (2.78%)
occurrences all number	1	0	0	0	0	1	1	1
Hypoaesthesia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	1	0	0	0	0	0	1
Tremor
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	2	0	0	0	0	0	1
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	1 / 20 (5.00%)	1 / 20 (5.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	6	1	2	2	0	1	0
Leukopenia
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	6	0	1	1	0	0	0
Anaemia
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	1	0	0	0	0	0	1
Macrocytosis
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Monocytopenia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	3	1	1	0
Ear pain
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Eye disorders
Eye pain
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Vision blurred
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)	7 / 40 (17.50%)	4 / 36 (11.11%)
occurrences all number	1	0	2	1	4	1	8	4
Flatulence
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	3 / 20 (15.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)	3 / 40 (7.50%)	1 / 36 (2.78%)
occurrences all number	0	0	1	3	3	1	3	4
Constipation
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	2	1	0	1	2
Haemorrhoids
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0
Nausea
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)	5 / 40 (12.50%)	2 / 36 (5.56%)
occurrences all number	0	1	0	2	4	5	5	2
Abdominal pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	2 / 40 (5.00%)	3 / 36 (8.33%)
occurrences all number	0	0	0	0	0	1	2	3
Periodontal disease
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Hiatus hernia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	0	2	0	1	0	0	0
Rash
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	5 / 20 (25.00%)	1 / 20 (5.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	1 / 40 (2.50%)	3 / 36 (8.33%)
occurrences all number	1	1	5	1	2	0	1	5
Ecchymosis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0
Erythema
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	1	0	0	2
Blister
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	1	0	0	0	1	0	1
Skin ulcer
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	0	0	2	0	1
Onychomadesis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Rash erythematous
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Ingrowing nail
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	3 / 40 (7.50%)	0 / 36 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0
Renal and urinary disorders
Pyuria
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	0	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 17 (17.65%)	1 / 16 (6.25%)	1 / 20 (5.00%)	0 / 20 (0.00%)	2 / 21 (9.52%)	3 / 20 (15.00%)	5 / 40 (12.50%)	6 / 36 (16.67%)
occurrences all number	3	2	6	0	2	5	5	10
Muscle spasms
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	2 / 36 (5.56%)
occurrences all number	1	1	2	0	1	0	3	3
Musculoskeletal pain
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	2 / 36 (5.56%)
occurrences all number	1	0	2	2	1	0	3	3
Pain in extremity
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	3 / 20 (15.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	4 / 40 (10.00%)	3 / 36 (8.33%)
occurrences all number	0	0	4	2	1	1	4	5
Rheumatoid arthritis
subjects affected / exposed	1 / 17 (5.88%)	3 / 16 (18.75%)	3 / 20 (15.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	3 / 20 (15.00%)	3 / 40 (7.50%)	4 / 36 (11.11%)
occurrences all number	1	3	3	3	2	3	3	5
Back pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	5 / 20 (25.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)	7 / 40 (17.50%)	4 / 36 (11.11%)
occurrences all number	0	0	0	5	2	2	7	4
Bursitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	2	1	1	0	1
Joint swelling
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	0	0	0	1	2	0	2	1
Osteoarthritis
subjects affected / exposed	1 / 17 (5.88%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	1	1	0	1	0	0	2	1
Fibromyalgia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0
Neck pain
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	2	0	0	0	0	0	2
Sacroiliitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Tendon calcification
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Rheumatoid nodule
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	1 / 36 (2.78%)
occurrences all number	0	1	0	0	0	0	1	1
Spinal osteoarthritis
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	1	0	0	0	0	0	2
Myalgia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	1	3
Bone pain
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	0	2
Intervertebral disc protrusion
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	0	2
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 17 (5.88%)	3 / 16 (18.75%)	1 / 20 (5.00%)	2 / 20 (10.00%)	3 / 21 (14.29%)	3 / 20 (15.00%)	5 / 40 (12.50%)	3 / 36 (8.33%)
occurrences all number	1	3	1	2	3	4	7	4
Cellulitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	1	0	1	4	1	0	1	3
Ear infection
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	0	1	1	2	1	0	2	1
Herpes zoster
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	1	0	1	1	0	0
Influenza
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	3 / 40 (7.50%)	2 / 36 (5.56%)
occurrences all number	1	0	1	0	1	0	3	2
Nasopharyngitis
subjects affected / exposed	2 / 17 (11.76%)	2 / 16 (12.50%)	1 / 20 (5.00%)	6 / 20 (30.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	3 / 40 (7.50%)	3 / 36 (8.33%)
occurrences all number	2	2	3	10	0	1	3	5
Oral herpes
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	2	3	1	0	1	2
Otitis media
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	0	2	1	1	0	0	1	0
Sinusitis
subjects affected / exposed	1 / 17 (5.88%)	2 / 16 (12.50%)	1 / 20 (5.00%)	3 / 20 (15.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	4 / 40 (10.00%)	6 / 36 (16.67%)
occurrences all number	1	3	1	3	0	2	4	7
Upper respiratory tract infection
subjects affected / exposed	4 / 17 (23.53%)	3 / 16 (18.75%)	3 / 20 (15.00%)	3 / 20 (15.00%)	9 / 21 (42.86%)	2 / 20 (10.00%)	7 / 40 (17.50%)	5 / 36 (13.89%)
occurrences all number	6	3	3	3	12	2	10	9
Urinary tract infection
subjects affected / exposed	2 / 17 (11.76%)	3 / 16 (18.75%)	2 / 20 (10.00%)	1 / 20 (5.00%)	6 / 21 (28.57%)	2 / 20 (10.00%)	5 / 40 (12.50%)	5 / 36 (13.89%)
occurrences all number	3	5	2	3	24	2	12	11
Gastroenteritis viral
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	0	0	0	1	2	0	2	3
Pharyngitis
subjects affected / exposed	2 / 17 (11.76%)	1 / 16 (6.25%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	1 / 36 (2.78%)
occurrences all number	2	1	0	1	0	0	2	1
Pneumonia
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	2 / 40 (5.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	2	0	0	2	0
Fungal infection
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	2	1	1	0
Skin infection
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Staphylococcal infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	1	0	1	3
Respiratory tract infection
subjects affected / exposed	1 / 17 (5.88%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	1	0	0	0	0	0	0	1
Vaginitis bacterial
subjects affected / exposed	2 / 17 (11.76%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	0 / 36 (0.00%)
occurrences all number	2	0	0	0	0	0	1	0
Staphylococcal abscess
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Viral infection
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 40 (2.50%)	2 / 36 (5.56%)
occurrences all number	0	0	0	0	0	0	2	2
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 17 (0.00%)	2 / 16 (12.50%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	3 / 40 (7.50%)	1 / 36 (2.78%)
occurrences all number	0	2	1	0	0	0	3	1
Hyperlipidaemia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	3 / 40 (7.50%)	0 / 36 (0.00%)
occurrences all number	0	0	1	1	0	1	3	0
Hypokalaemia
subjects affected / exposed	0 / 17 (0.00%)	1 / 16 (6.25%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 40 (0.00%)	1 / 36 (2.78%)
occurrences all number	0	1	1	0	1	0	0	1
Hypoglycaemia
subjects affected / exposed	0 / 17 (0.00%)	0 / 16 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 21 (4.76%)	2 / 20 (10.00%)	0 / 40 (0.00%)	0 / 36 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

30 Nov 2010

Amendment 1 dated 30 November 2010 implemented the following changes: • Clarification that subjects were not monitored and observed in the clinic for at least 30 minutes post olokizumab administration • The stable MTX dose range was changed from 15 to 25 mg/week to 12.5 to 25 mg/week • The TB testing was performed using either the PPD test or Elispot (or QuantiFERON-TB GOLD if the Elispot test was not available) • Change in inclusion criteria to clarify that female subjects of childbearing potential must agree to use at least 2 forms of adequate contraception during the study and for 6 months (24 weeks) after their last dose of olokizumab • Clarification that all additional withdrawal and dose modifications based on laboratory abnormalities • All sc injections of olokizumab were to be administered by qualified study personnel and not just study nurses and the study facility must have had adequate arrangements in order to manage anaphylactic reactions • Addition that there was a potential interaction of olokizumab with hepatic cytochrome P450 enzymes so that close attention was to be paid to the effectiveness or toxicity of the subjects’ coadministered medication(s) known to be metabolized/eliminated by cytochrome P450 enzymes and/or sodium/taurocholate cotransporting polypeptide and dose adjustments made as needed • Clarification that the subjects could be in the sitting (instead of supine) position when vital signs were measured.

12 May 2011

Amendment 2 dated 12 May 2011 implemented the following changes: • Added information updates on clinical Studies RA0010 and RA0074 in the Introduction • Clarification in withdrawal criteria that if a subject developed three or more noninvasive nonmelanoma skin cancers, or any other malignancy, since the start of Study RA0056, he/she should be withdrawn from the study • Removal of the assessment of the Epstein-Barr Virus (EBV) viral load from the laboratory assessments at Visit 7 and Visit 25 and the Early Discontinuation Visit • Removal of the assessment of complements C3 and C4 from the laboratory hematology assessments; with footnotes specifying that the ESR was to be analyzed by the site and subjects should arrive at the study center in a fasted state for the blood draw for Apo B, Apo A-1, Lp(a) • Correction in equation used for the determination of DAS28 (CRP) • Addition of CSP code for the analysis of PK analysis samples • Clarification that the study facility must have adequate arrangements to manage anaphylactic reactions • Clarification that the CXR taken at Week 48 and every 72 weeks thereafter until study completion should be a plain posteroanterior CXR • Addition of a reference that the newly added RA-related events may be anticipated for subjects with RA as per the FDA’s Final Rule for Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans, 21 C.F.R. Parts 312 and 320, 2011.

15 Sep 2011

Amendment 3 dated 15 September 2011 implemented the following changes: • Clarification to allow MTX dose reductions/adjustments, but not dose increases, during the study and addition of the requirement for subjects to take folate supplementation during the study to minimize MTX toxicity • Clarification that exclusion of subjects with evidence of active or latent TB should be based on the Investigators’ medical judgement. • Clarification on minimum permissible timeframe between olokizumab doses to be 11 days • Clarification to allow concomitant medication dose reductions after Week 12 in subjects who have achieved a significant reduction in RA clinical disease activity based on the Investigator’s medical judgment • Clarification to allow intra-articular injection of hyaluronic acid after Week 12 • Clarification of those study visits where the subjects were required to attend in a fasted state • Update of the section on anticipated AEs for implementation of the FDA final rule • The CSP Section 11.6.5.1.2 regarding TB detection simplified.

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 clinical trial was terminated early as a result of a strategic UCB decision to out-license the study drug for further development. As a result, only small numbers of subjects were still in the study past the Week 48 time point.

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Clinical trials

Clinical Trial Results: A Phase 2 Multi-Center, Open-Label, Follow-Up Study to Assess The Long-Term Safety and Efficacy of CDP6038 Administered Subcutaneously to Subjects With Active Rheumatoid Arthritis Who completed Study RA0056

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with treatment-emergent adverse events (TEAEs)

Primary: Number of subjects with treatment-emergent adverse events (TEAEs)

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint count (C-reactive protein) (DAS28[CRP]) to Week 12 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Disease Activity Score-28-joint count (C-reactive protein) (DAS28[CRP]) to Week 12 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 24 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in DAS28(CRP) to Week 96 of Study RA0057

Secondary: The American College of Rheumatology (ACR) 20% (ACR20) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The American College of Rheumatology (ACR) 20% (ACR20) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: The ACR20 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: The ACR 50% (ACR50) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The ACR 50% (ACR50) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: The ACR50 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: The ACR 70% (ACR70) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The ACR 70% (ACR70) improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 12 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 24 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 48 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: The ACR70 improvement criteria response rate from Baseline (Week 0 of Study RA0056) to Week 96 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 12 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 12 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 24 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 24 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 48 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 48 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 96 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) <2.6 at Week 96 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 12 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 12 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 24 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 24 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 48 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 48 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 96 of Study RA0057

Secondary: Percentage of subjects with DAS28(CRP) ≤3.2 at Week 96 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Clinical Disease Activity Index (CDAI) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the CDAI to Week 96 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the Simplified Disease Activity Index (SDAI) to Week 48 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057

Secondary: Change from Baseline (Week 0 of Study RA0056) in the SDAI to Week 96 of Study RA0057

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 2 Multi-Center, Open-Label, Follow-Up Study to Assess The Long-Term Safety and Efficacy of CDP6038 Administered Subcutaneously to Subjects With Active Rheumatoid Arthritis Who completed Study RA0056