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Clinical Trial Results:
A Phase IIB , Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo/Active Controlled Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection With or Without Methotrexate in Subjects with Moderate to Severe Rheumatoid Arthritis with Inadequate Response to Methotrexate

Summary
EudraCT number	2010-023956-99
Trial protocol	HU BE NL DE CZ ES IT
Global end of trial date	10 Jun 2015

Results information
Results version number	v1(current)
This version publication date	20 Feb 2023
First version publication date	20 Feb 2023
Other versions

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

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Trial information

Top of page

Sponsor protocol code

IM133-001

ISRCTN number

-

US NCT number

NCT01373151

WHO universal trial number (UTN)

-

Sponsor organisation name

CSL Behring

Sponsor organisation address

1020 First Avenue, King of Prussia, United States, 19406

Public contact

Study Director, CSL Behring, +1 610-878-4000, clinicaltrials@cslbehring.com

Scientific contact

Study Director, CSL Behring, +1 610-878-4000, clinicaltrials@cslbehring.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

10 Jun 2015

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

10 Jun 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

To compare the efficacy of BMS-945429 SC versus placebo (PBO) on a background of MTX as assessed by ACR20 response rates at 12 weeks.

Protection of trial subjects

Standard of care procedures were employed in order to minimize harm to the patients. Study staff continuously interacted with the patients and were thoroughly trained on patient rights as well as medically trained to handle any adverse events. Study staff were well-informed on procedures to handle subjects from pre-screening through the completion of the study. All patients were explained the alternatives to being a part of the study. Procedures were also in place to ensure there was no undue coercion during the informed consent process.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

15 Jun 2011

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 20

Country: Number of subjects enrolled

Spain: 10

Country: Number of subjects enrolled

Belgium: 10

Country: Number of subjects enrolled

Czech Republic: 10

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Hungary: 16

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Argentina: 102

Country: Number of subjects enrolled

Brazil: 32

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

Japan: 58

Country: Number of subjects enrolled

Korea, Republic of: 4

Country: Number of subjects enrolled

Mexico: 70

Country: Number of subjects enrolled

Russian Federation: 39

Country: Number of subjects enrolled

South Africa: 18

Country: Number of subjects enrolled

Taiwan: 7

Country: Number of subjects enrolled

United States: 10

Worldwide total number of subjects

418

EEA total number of subjects

76

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

366

From 65 to 84 years

52

85 years and over

0

Subject disposition

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Recruitment details

-

Screening details

A total of 841 were enrolled and 418 were randomized and treated with study drug.

Period 1 title

Period 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo+MTX

Arm description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Clazakizumab(25)+MTX

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(100)

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(100)+MTX

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(200)

Arm description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(200)+MTX

Arm description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

ADA+MTX

Arm description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Arm type

Active comparator

Investigational medicinal product name

ADALIMUMAB

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Injection, Subcutaneous

Number of subjects in period 1	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Started	61	59	60	60	59	60	59
Completed	56	59	56	59	54	56	59
Not completed	5	0	4	1	5	4	0
Consent withdrawn by subject	2	-	3	1	-	1	-
Adverse event, non-fatal	-	-	1	-	4	3	-
Lack of efficacy	3	-	-	-	1	-	-

Period 2 title

Period 2

Is this the baseline period?

No

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo+MTX

Arm description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Clazakizumab(25)+MTX

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(100)

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(100)+MTX

Arm description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(200)

Arm description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

Clazakizumab(200)+MTX

Arm description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Arm type

Experimental

Investigational medicinal product name

Clazakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

BMS-945429: Injection, Subcutaneous

ADA+MTX

Arm description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Arm type

Active comparator

Investigational medicinal product name

ADALIMUMAB

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Injection, Subcutaneous

Number of subjects in period 2 ^[1]	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Started	56	58	56	59	54	55	59
Completed	47	57	52	54	52	55	54
Not completed	9	1	4	5	2	0	5
Consent withdrawn by subject	-	-	-	1	-	-	-
Adverse event, non-fatal	-	-	3	3	-	-	1
Unknown	-	-	1	-	-	-	1
subject request to discontinue	-	1	-	-	-	-	-
Lack of efficacy	9	-	-	1	2	-	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only subjects treated in Period 2 were counted.

Baseline characteristics

Top of page

Reporting group title

Placebo+MTX

Reporting group description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(25)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)+MTX

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

ADA+MTX

Reporting group description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Reporting group values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX	Total
Number of subjects	61	59	60	60	59	60	59	418
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0
Adults (18-64 years)	54	56	47	52	51	55	51	366
From 65-84 years	7	3	13	8	8	5	8	52
85 years and over	0	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	51.4 ± 11.03	47.4 ± 10.97	55.0 ± 12.21	49.9 ± 13.95	50.0 ± 12.53	46.4 ± 11.91	52.8 ± 11.41	-
Gender categorical
Units: Subjects
Female	46	46	52	53	49	49	48	343
Male	15	13	8	7	10	11	11	75

End points

Top of page

Reporting group title

Placebo+MTX

Reporting group description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(25)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)+MTX

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

ADA+MTX

Reporting group description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Reporting group title

Placebo+MTX

Reporting group description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(25)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)+MTX

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

ADA+MTX

Reporting group description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Primary: Percent of Participants Achieving an American College of Rheumatology (ACR) 20% Response Rate

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End point title

Percent of Participants Achieving an American College of Rheumatology (ACR) 20% Response Rate ^[1]

End point description

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

End point type

Primary

End point timeframe

At 12 Weeks

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: Descriptive statistics were used.

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)	39.3	76.3	55.0	73.3	61.0	60.0	76.3

No statistical analyses for this end point

Secondary: Percent of Participants With ACR 20 Response

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End point title

Percent of Participants With ACR 20 Response

End point description

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

End point type

Secondary

End point timeframe

At 24 weeks

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)	37.7	81.4	58.3	65.0	57.6	66.7	66.1

No statistical analyses for this end point

Secondary: Percent of Participants Achieving ACR 50 Response Rate

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End point title

Percent of Participants Achieving ACR 50 Response Rate

End point description

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
12 weeks	21.3	49.2	26.7	43.3	28.8	26.7	30.5
24 weeks	16.4	47.5	36.7	46.7	33.9	43.3	47.5

No statistical analyses for this end point

Secondary: Percent of Participants Achieving ACR 70 Response Rate

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End point title

Percent of Participants Achieving ACR 70 Response Rate

End point description

The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
12 weeks	8.2	18.6	13.3	26.7	11.9	13.3	11.9
24 weeks	6.6	27.1	16.7	40.0	25.4	30.0	18.6

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Disease Activity as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

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End point title

Mean Change From Baseline in Disease Activity as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)

End point description

DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[2]	59 ^[3]	60 ^[4]	60 ^[5]	59 ^[6]	60 ^[7]	59 ^[8]
Units: score on a scale
arithmetic mean (standard error)
12 weeks	-1.15 ± 0.1652	-2.65 ± 0.1610	-2.29 ± 0.1603	-2.68 ± 0.1597	-2.34 ± 0.1665	-2.52 ± 0.1610	-2.04 ± 0.1647
24 weeks	-1.69 ± 0.1825	-3.01 ± 0.1684	-2.60 ± 0.1719	-3.06 ± 0.1713	-2.55 ± 0.1769	-2.95 ± 0.1706	-2.52 ± 0.1769

Notes
[2] - n=52 for week 12; n=43 for week 24
[3] - n=54 for week 12; n=56 for week 24
[4] - n=55 for week 12; n=50 for week 24
[5] - n=56 for week 12; n=51 for week 24
[6] - n=50 for week 12; n=47 for week 24
[7] - n=54 for week 12; n=53 for week 24
[8] - n=54 for week 12; n=49 for week 24

No statistical analyses for this end point

Secondary: Percent of Participants With Remission by DAS28-CRP

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End point title

Percent of Participants With Remission by DAS28-CRP

End point description

DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
week 12	1.6	35.6	21.7	35.0	25.4	26.7	20.3
week 24	11.5	49.2	25.0	40.0	35.6	41.7	23.7

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Clinical Disease Activity Index (CDAI)

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End point title

Mean Change From Baseline in Clinical Disease Activity Index (CDAI)

End point description

CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76. CDAI <= 2.8 = Remission; CDAI > 2.8 and <= 10 = Low Disease Activity; CDAI > 10 and <= 22 = Moderate Disease Activity; CDAI > 22 = High Disease Activity

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[9]	59 ^[10]	60 ^[11]	60 ^[12]	59 ^[13]	60 ^[14]	59 ^[15]
Units: score on a scale
arithmetic mean (standard error)
week 12	-14.5 ± 1.727	-22.7 ± 1.686	-17.7 ± 1.687	-23.1 ± 1.701	-19.8 ± 1.738	-21.0 ± 1.697	-22.4 ± 1.702
week 24	-20.3 ± 1.703	-26.1 ± 1.587	-22.0 ± 1.613	-26.9 ± 1.622	-21.7 ± 1.643	-25.6 ± 1.606	-26.2 ± 1.631

Notes
[9] - n=54 for week 12; n=45 for week 24
[10] - n=58 for week 12; n=57 for week 24
[11] - n=55 for week 12; n=51 for week 24
[12] - n=56 for week 12; n=52 for week 24
[13] - n=52 for week 12; n=50 for week 24
[14] - n=55 for week 12; n=54 for week 24
[15] - n=57 for week 12; n=52 for week 24

No statistical analyses for this end point

Secondary: Percent of Participants With Remission by CDAI

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End point title

Percent of Participants With Remission by CDAI

End point description

CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76. CDAI <= 2.8 = Remission; CDAI > 2.8 and <= 10 = Low Disease Activity; CDAI > 10 and <= 22 = Moderate Disease Activity; CDAI > 22 = High Disease Activity

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
week 12	3.3	11.9	8.3	8.3	3.4	3.3	8.5
week 24	1.6	15.3	6.7	21.7	6.8	20.0	8.5

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Simplified Disease Activity Index (SDAI)

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End point title

Mean Change From Baseline in Simplified Disease Activity Index (SDAI)

End point description

SDAI is a composite index for assessing disease activity. SDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86. 0.0 - 3.3 = Remission; 3.4 - 11.0 = Low Activity; 11.1 - 26.0 = Moderate Activity; 26.1 - 86.0 = High Activity

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[16]	59 ^[17]	60 ^[18]	60 ^[19]	59 ^[20]	60 ^[21]	59 ^[22]
Units: score on a scale
arithmetic mean (standard error)
week 12	-14.5 ± 1.794	-24.9 ± 1.749	-20.4 ± 1.745	-25.3 ± 1.734	-22.2 ± 1.811	-23.3 ± 1.747	-23.2 ± 1.785
week 24	-20.6 ± 1.812	-28.4 ± 1.670	-24.5 ± 1.704	-29.1 ± 1.698	-23.5 ± 1.755	-27.6 ± 1.691	-27.6 ± 1.752

Notes
[16] - n=52 for week 12; n=43 for week 24
[17] - n=54 for week 12; n=56 for week 24
[18] - n=54 for week 12; n=50 for week 24
[19] - n=56 for week 12; n=51 for week 24
[20] - n=50 for week 12; n=47 for week 24
[21] - n=54 for week 12; n=53 for week 24
[22] - n=54 for week 12; n=49 for week 24

No statistical analyses for this end point

Secondary: Percent of Participants With Remission by SDAI

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End point title

Percent of Participants With Remission by SDAI

End point description

SDAI is a composite index for assessing disease activity. SDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86. 0.0 - 3.3 = Remission; 3.4 - 11.0 = Low Activity; 11.1 - 26.0 = Moderate Activity; 26.1 - 86.0 = High Activity

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
week 12	1.6	11.9	8.3	8.3	6.8	5.0	10.2
week 24	4.9	18.6	6.7	20.0	6.8	23.3	8.5

No statistical analyses for this end point

Secondary: Percent of Participants With Remission Rate by Boolean Definition

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End point title

Percent of Participants With Remission Rate by Boolean Definition

End point description

Boolean-based definition: At any time point, a patient must satisfy all of the following: TJC ≤1 (0-28); SJC ≤1 (0-28); CRP ≤1 mg/dl; Patient Global Assessment ≤1 (on a 0-10 scale)

End point type

Secondary

End point timeframe

At weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61	59	60	60	59	60	59
Units: percentage of participants
number (not applicable)
week 12	3.3	8.5	6.7	10.0	1.7	5.0	5.1
week 24	1.6	10.2	5.0	13.3	5.1	18.3	10.2

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Disability Index

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End point title

Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Disability Index

End point description

Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[23]	59 ^[24]	60 ^[25]	60 ^[26]	59 ^[27]	60 ^[28]	59 ^[29]
Units: score on a scale
arithmetic mean (standard error)
week 12	-0.44 ± 0.0827	-0.66 ± 0.0801	-0.47 ± 0.0807	-0.70 ± 0.0811	-0.51 ± 0.0834	-0.60 ± 0.0807	-0.60 ± 0.0819
week 24	-0.62 ± 0.0861	-0.68 ± 0.0806	-0.64 ± 0.0823	-0.79 ± 0.0823	-0.60 ± 0.0840	-0.71 ± 0.0811	-0.66 ± 0.0833

Notes
[23] - n=54 for week 12; n=44 for week 24
[24] - n=59 for week 12; n=58 for week 24
[25] - n=56 for week 12; n=51 for week 24
[26] - n=57 for week 12; n=53 for week 24
[27] - n=52 for week 12; n=50 for week 24
[28] - n=56 for week 12; n=56 for week 24
[29] - n=58 for week 12; n=53 for week 24

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Short Form 36 (SF-36) as Measured by Physical and Mental Components

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End point title

Mean Change From Baseline in Short Form 36 (SF-36) as Measured by Physical and Mental Components

End point description

The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status.

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[30]	59 ^[31]	60 ^[32]	60 ^[33]	59 ^[34]	60 ^[35]	59 ^[36]
Units: score on a scale
arithmetic mean (standard error)
Mental component (week 12)	5.3 ± 1.274	5.9 ± 1.240	4.5 ± 1.251	7.3 ± 1.244	4.0 ± 1.283	5.7 ± 1.230	6.4 ± 1.250
Mental component (week 24)	6.0 ± 1.327	6.4 ± 1.208	6.6 ± 1.247	7.5 ± 1.247	5.3 ± 1.271	8.0 ± 1.219	7.1 ± 1.246
Physical component (week 12)	4.0 ± 1.030	7.5 ± 0.999	7.3 ± 1.010	9.5 ± 1.002	6.8 ± 1.028	7.3 ± 0.994	8.4 ± 1.006
Physical component (week 24)	6.2 ± 1.149	8.6 ± 1.045	9.4 ± 1.080	10.9 ± 1.076	7.7 ± 1.094	8.2 ± 1.057	8.2 ± 1.077

Notes
[30] - n=55 for week 12; n=46 for week 24
[31] - n=58 for week 12; n=59 for week 24
[32] - n=57 for week 12; n=54 for week 24
[33] - n=58 for week 12; n=54 for week 24
[34] - n=55 for week 12; n=53 for week 24
[35] - n=59 for week 12; n=57 for week 24
[36] - n=58 for week 12; n=55 for week 24

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Fatigue Severity (VAS) Score

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End point title

Mean Change From Baseline in Fatigue Severity (VAS) Score

End point description

A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[37]	59 ^[38]	60 ^[39]	60 ^[40]	59 ^[41]	60 ^[42]	59 ^[43]
Units: score on a scale
arithmetic mean (standard error)
week 12	-14.3 ± 3.146	-20.8 ± 3.060	-19.4 ± 3.077	-27.4 ± 3.077	-21.7 ± 3.180	-18.6 ± 3.056	-26.3 ± 3.080
week 24	-12.9 ± 3.306	-23.9 ± 3.052	-22.3 ± 3.131	-31.3 ± 3.103	-17.7 ± 3.184	-23.4 ± 3.056	-27.0 ± 3.134

Notes
[37] - n=54 for week 12; n=45 for week 24
[38] - n=58 for week 12; n=57 for week 24
[39] - n=56 for week 12; n=51 for week 24
[40] - n=57 for week 12; n=54 for week 24
[41] - n=52 for week 12; n=50 for week 24
[42] - n=57 for week 12; n=56 for week 24
[43] - n=58 for week 12; n=53 for week 24

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Scores

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End point title

Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Scores

End point description

The WPAI yeilds four types of scores: 1.Absenteeism (work time missed) 2.Presenteesism (impairment at work / reduced on-the-job effectiveness) 3.Work productivty loss (overall work impairment / absenteeism plus presenteeism) 4.Activity Impairment WPAI outcomes are expressed as impairment percentages with each subscale score ranging from 0-100. The subscale scores are added and averaged to produce a total WPAI score between 0-100. Higher scores indicate greater impairment and less productivity.

End point type

Secondary

End point timeframe

Baseline, weeks 12 and 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[44]	59 ^[45]	60 ^[46]	60 ^[47]	59 ^[48]	60 ^[49]	59 ^[50]
Units: score on a scale
arithmetic mean (standard error)
week 12	-9.6 ± 3.273	-2.2 ± 3.443	-8.7 ± 3.673	-12.0 ± 3.081	-13.7 ± 3.285	-10.0 ± 3.575	-11.7 ± 6.281
week 24	-10.7 ± 4.033	-1.8 ± 3.893	-17.1 ± 4.200	-12.1 ± 3.448	-5.9 ± 3.788	-12.6 ± 3.938	-4.7 ± 6.379

Notes
[44] - n=22 for week 12; n=18 for week 24
[45] - n=20 for week 12; n=20 for week 24
[46] - n=18 for week 12; n=17 for week 24
[47] - n=25 for week 12; n=25 for week 24
[48] - n=22 for week 12; n=21 for week 24
[49] - n=19 for week 12; n=19 for week 24
[50] - n=6 for week 12; n=7 for week 24

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Radiographic (MRI) Progression of Synovitis, Osteitis (Bone Marrow Edema), Bone Erosion and Cartilage Loss (Joint-space Narrowing)

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End point title

Mean Change From Baseline in Radiographic (MRI) Progression of Synovitis, Osteitis (Bone Marrow Edema), Bone Erosion and Cartilage Loss (Joint-space Narrowing)

End point description

End point type

Secondary

End point timeframe

Baseline and week 12

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	61 ^[51]	59 ^[52]	60 ^[53]	60 ^[54]	59 ^[55]	60 ^[56]	59 ^[57]
Units: cubic millimeters
arithmetic mean (standard error)
Erosion	1.3 ± 0.352	0.4 ± 0.341	1.1 ± 0.356	0.3 ± 0.334	1.0 ± 0.369	-0.2 ± 0.341	-0.5 ± 0.348
Edema	0.2 ± 1.009	-6.4 ± 0.993	-2.6 ± 1.015	-4.7 ± 0.998	-4.6 ± 1.036	-5.1 ± 0.993	-3.1 ± 1.008
Synovitis	-0.5 ± 0.436	-2.5 ± 0.427	-1.4 ± 0.440	-2.2 ± 0.426	-2.9 ± 0.447	-2.5 ± 0.427	-2.9 ± 0.435
Narrowing	0.1 ± 0.133	-0.1 ± 0.130	0.2 ± 0.135	-0.1 ± 0.126	0.1 ± 0.139	0.0 ± 0.129	-0.2 ± 0.132

Notes
[51] - n=51
[52] - n=50 for erosion and narrowing; n=51 for edema and syovitis
[53] - n=50
[54] - n=59
[55] - n=48 for erosion and narrowing; n=50 for edema and synovitis
[56] - n=54
[57] - n=52

No statistical analyses for this end point

Secondary: Mean Change From Baseline in Radiographic (X-ray) Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijde Total Score

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End point title

Mean Change From Baseline in Radiographic (X-ray) Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijde Total Score

End point description

The Sharp-van der Heijde total score ranges from 0-528. Scores for erosion range from 0 to 5 in the hands and 0 to 10 in the feet and reflect erosion size, with 0 defined as no erosion and 3 defined as a large erosion passing the midline of the joint. If there is > 1 erosion per joint, scores can be combined to give a maximum score of 5 per joint in the hands and 10 per joint in the feet (a maximum of 5 at each side of the joint). Joint space narrowing scores vary from 0 to 4 in both the hands and feet, with 0 being normal and 4 being the absence of joint space with evident ankylosis or subluxation. Gross osteolysis and pencil-in-cup change are scored separately and, if present, are assigned the maximum score for erosion and joint space narrowing for the same affected joint. Higher scores indicate increased joint damage.

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Number of subjects analysed	44	59	54	54	53	53	54
Units: score on a scale
arithmetic mean (standard error)	1.8 ± 0.353	0.3 ± 0.320	0.0 ± 0.327	0.1 ± 0.324	0.1 ± 0.330	0.1 ± 0.336	0.1 ± 0.333

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 48 weeks per participant

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Placebo+MTX

Reporting group description

BMS-945429 (Clazakizumab)Placebo/BMS-945429+Methotrexate+Adalimumab Placebo BMS-945429 Placebo: Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(25)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(100)+MTX

Reporting group description

BMS-945429 + Methotrexate + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48 Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

Clazakizumab(200)+MTX

Reporting group description

BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo BMS-945429: Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks Methotrexate Placebo: Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only Methotrexate: Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only Adalimumab Placebo: Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks

Reporting group title

ADA+MTX

Reporting group description

Adalimumab(ADA) + Methotrexate Methotrexate: Tablets, Oral, 15 mg, Weekly, 48 weeks Adalimumab: Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

Serious adverse events	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 61 (3.28%)	5 / 59 (8.47%)	5 / 60 (8.33%)	5 / 60 (8.33%)	8 / 59 (13.56%)	5 / 60 (8.33%)	3 / 59 (5.08%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Lung disorder
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Psychiatric disorders
Depression
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	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
Suicide attempt
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Aspartate aminotransferase increased
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Foot fracture
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Humerus fracture
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Medication error
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Overdose
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Atrial fibrillation
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Coronary artery disease
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Mitral valve incompetence
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Headache
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Eye disorders
Cataract
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
Abdominal wall haematoma
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Diarrhoea
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Tubulointerstitial nephritis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	2 / 60 (3.33%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 61 (0.00%)	2 / 59 (3.39%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	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
Pneumonia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 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
Atypical pneumonia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Bursitis infective
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Herpes zoster
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)
occurrences causally related to treatment / all	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
Infective tenosynovitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Pneumocystis jiroveci pneumonia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Sepsis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Traumatic haematoma
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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
Urinary tract infection
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences causally related to treatment / all	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

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

Non-serious adverse events	Placebo+MTX	Clazakizumab(25)+MTX	Clazakizumab(100)	Clazakizumab(100)+MTX	Clazakizumab(200)	Clazakizumab(200)+MTX	ADA+MTX
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 61 (39.34%)	43 / 59 (72.88%)	43 / 60 (71.67%)	51 / 60 (85.00%)	43 / 59 (72.88%)	50 / 60 (83.33%)	35 / 59 (59.32%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 61 (3.28%)	11 / 59 (18.64%)	2 / 60 (3.33%)	13 / 60 (21.67%)	1 / 59 (1.69%)	1 / 60 (1.67%)	3 / 59 (5.08%)
occurrences all number	2	11	2	13	1	1	3
Aspartate aminotransferase increased
subjects affected / exposed	0 / 61 (0.00%)	8 / 59 (13.56%)	0 / 60 (0.00%)	14 / 60 (23.33%)	0 / 59 (0.00%)	12 / 60 (20.00%)	2 / 59 (3.39%)
occurrences all number	0	8	0	14	0	12	2
Gamma-glutamyl transferease increased
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	2 / 60 (3.33%)	4 / 60 (6.67%)	0 / 59 (0.00%)	2 / 60 (3.33%)	2 / 59 (3.39%)
occurrences all number	1	0	2	4	0	2	2
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	3 / 60 (5.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences all number	0	0	3	1	0	1	0
Overdose
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	1	0	0	3	0	0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	1 / 60 (1.67%)	4 / 60 (6.67%)	6 / 59 (10.17%)	2 / 60 (3.33%)	2 / 59 (3.39%)
occurrences all number	1	0	1	4	6	2	2
Nervous system disorders
Headache
subjects affected / exposed	5 / 61 (8.20%)	2 / 59 (3.39%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	2 / 60 (3.33%)	1 / 59 (1.69%)
occurrences all number	5	2	0	0	1	2	1
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	0 / 61 (0.00%)	8 / 59 (13.56%)	9 / 60 (15.00%)	11 / 60 (18.33%)	14 / 59 (23.73%)	9 / 60 (15.00%)	1 / 59 (1.69%)
occurrences all number	0	8	9	11	14	9	1
Ejection site erythema
subjects affected / exposed	0 / 61 (0.00%)	2 / 59 (3.39%)	8 / 60 (13.33%)	15 / 60 (25.00%)	10 / 59 (16.95%)	9 / 60 (15.00%)	2 / 59 (3.39%)
occurrences all number	0	2	8	15	10	9	2
Injection site rash
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	8 / 60 (13.33%)	8 / 60 (13.33%)	2 / 59 (3.39%)	8 / 60 (13.33%)	0 / 59 (0.00%)
occurrences all number	0	1	8	8	2	8	0
Injection site dermatitis
subjects affected / exposed	0 / 61 (0.00%)	4 / 59 (6.78%)	3 / 60 (5.00%)	4 / 60 (6.67%)	4 / 59 (6.78%)	7 / 60 (11.67%)	0 / 59 (0.00%)
occurrences all number	0	4	3	4	4	7	0
Asthenia
subjects affected / exposed	2 / 61 (3.28%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	3 / 60 (5.00%)	1 / 59 (1.69%)
occurrences all number	2	1	0	0	1	3	1
Injection site hypersensitivity
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	3 / 60 (5.00%)	2 / 60 (3.33%)	2 / 59 (3.39%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences all number	0	0	3	2	2	1	0
Injection site papule
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	2 / 60 (3.33%)	0 / 60 (0.00%)	1 / 59 (1.69%)	3 / 60 (5.00%)	0 / 59 (0.00%)
occurrences all number	0	1	2	0	1	3	0
Injection site pruritis
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	4 / 60 (6.67%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences all number	0	1	0	4	0	1	0
Injection site macule
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	1 / 59 (1.69%)	3 / 60 (5.00%)	0 / 59 (0.00%)
occurrences all number	0	0	1	0	1	3	0
Injection site pain
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	1 / 60 (1.67%)	3 / 59 (5.08%)
occurrences all number	0	0	0	1	0	1	3
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 61 (0.00%)	2 / 59 (3.39%)	4 / 60 (6.67%)	2 / 60 (3.33%)	4 / 59 (6.78%)	1 / 60 (1.67%)	2 / 59 (3.39%)
occurrences all number	0	2	4	2	4	1	2
Leukopenia
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	3 / 60 (5.00%)	2 / 60 (3.33%)	4 / 59 (6.78%)	3 / 60 (5.00%)	0 / 59 (0.00%)
occurrences all number	1	0	3	2	4	3	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 61 (1.64%)	3 / 59 (5.08%)	1 / 60 (1.67%)	3 / 60 (5.00%)	2 / 59 (3.39%)	3 / 60 (5.00%)	6 / 59 (10.17%)
occurrences all number	1	3	1	3	2	3	6
Nausea
subjects affected / exposed	1 / 61 (1.64%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 59 (1.69%)	2 / 60 (3.33%)	3 / 59 (5.08%)
occurrences all number	1	3	0	0	1	2	3
Dyspepsia
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	1 / 60 (1.67%)	1 / 59 (1.69%)	0 / 60 (0.00%)	3 / 59 (5.08%)
occurrences all number	0	1	0	1	1	0	3
Skin and subcutaneous tissue disorders
Dermatitis allergic
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	3 / 60 (5.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)
occurrences all number	0	0	3	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	3 / 60 (5.00%)	0 / 59 (0.00%)
occurrences all number	0	0	0	0	0	3	0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 59 (0.00%)	1 / 60 (1.67%)	4 / 59 (6.78%)
occurrences all number	0	0	0	1	0	1	4
Infections and infestations
Nasopharyngitis
subjects affected / exposed	4 / 61 (6.56%)	2 / 59 (3.39%)	3 / 60 (5.00%)	4 / 60 (6.67%)	3 / 59 (5.08%)	7 / 60 (11.67%)	2 / 59 (3.39%)
occurrences all number	4	2	3	4	3	7	2
Upper respiratory tract infection
subjects affected / exposed	7 / 61 (11.48%)	5 / 59 (8.47%)	1 / 60 (1.67%)	3 / 60 (5.00%)	7 / 59 (11.86%)	1 / 60 (1.67%)	0 / 59 (0.00%)
occurrences all number	7	5	1	3	7	1	0
Pharyngitis
subjects affected / exposed	5 / 61 (8.20%)	2 / 59 (3.39%)	3 / 60 (5.00%)	3 / 60 (5.00%)	3 / 59 (5.08%)	3 / 60 (5.00%)	3 / 59 (5.08%)
occurrences all number	5	2	3	3	3	3	3
Urinary tract infection
subjects affected / exposed	4 / 61 (6.56%)	5 / 59 (8.47%)	1 / 60 (1.67%)	2 / 60 (3.33%)	2 / 59 (3.39%)	5 / 60 (8.33%)	1 / 59 (1.69%)
occurrences all number	4	5	1	2	2	5	1
Bronchitis
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	2 / 60 (3.33%)	0 / 60 (0.00%)	2 / 59 (3.39%)	2 / 60 (3.33%)	3 / 59 (5.08%)
occurrences all number	0	1	2	0	2	2	3
Herpes zoster
subjects affected / exposed	0 / 61 (0.00%)	1 / 59 (1.69%)	1 / 60 (1.67%)	1 / 60 (1.67%)	3 / 59 (5.08%)	0 / 60 (0.00%)	3 / 59 (5.08%)
occurrences all number	0	1	1	1	3	0	3
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	2 / 61 (3.28%)	7 / 59 (11.86%)	7 / 60 (11.67%)	5 / 60 (8.33%)	5 / 59 (8.47%)	9 / 60 (15.00%)	2 / 59 (3.39%)
occurrences all number	2	7	7	5	5	9	2
Dyslipidaemia
subjects affected / exposed	1 / 61 (1.64%)	7 / 59 (11.86%)	4 / 60 (6.67%)	2 / 60 (3.33%)	2 / 59 (3.39%)	4 / 60 (6.67%)	1 / 59 (1.69%)
occurrences all number	1	7	4	2	2	4	1
Hypertriglyceridaemia
subjects affected / exposed	2 / 61 (3.28%)	1 / 59 (1.69%)	1 / 60 (1.67%)	2 / 60 (3.33%)	1 / 59 (1.69%)	1 / 60 (1.67%)	3 / 59 (5.08%)
occurrences all number	2	1	1	2	1	1	3
Hyperlipidaemia
subjects affected / exposed	0 / 61 (0.00%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	2 / 59 (3.39%)
occurrences all number	0	3	0	0	0	1	2

More information

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Were there any global substantial amendments to the protocol? Yes

11 Jan 2011

To permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research.

08 Mar 2011

Permitted additional safety monitoring of abnormal liver function testing .

14 Nov 2011

Changes were made to clarify and take into consideration legal guidelines based upon feedback from regulatory agencies and study personnel.

28 Feb 2014

Addressed the dose selection for the long-term phase of the protocol.

Were there any global interruptions to the trial? No

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

None reported

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