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Clinical Trial Results:
A Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of CAM-3001 in participants with rheumatoid arthritis (RA).

Summary
EudraCT number	2009-014735-20
Trial protocol	LV EE HU CZ LT PL BG
Global end of trial date	27 Jul 2012

Results information
Results version number	v1(current)
This version publication date	07 Jan 2017
First version publication date	07 Jan 2017
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

MI-CP219

ISRCTN number

US NCT number

NCT01050998

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

Milstein Building, Granta Park, Cambridge, CB21 6GH United Kingdom, United Kingdom,

Public contact

Marius Albulescu, Associate Medical Director, MedImmune, LLC, +1 3013980000, albulescum@medimmune.com

Scientific contact

Marius Albulescu, Associate Medical Director, MedImmune, LLC, +1 3013980000, albulescum@medimmune.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

27 Jul 2012

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Jul 2012

Was the trial ended prematurely?

Main objective of the trial

Primary objectives of this study were to evaluate the safety, tolerability, and efficacy of multiple doses of mavrilimumab administered subcutaneous (SC) in participants with at least moderately active rheumatoid arthritis (RA).

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Feb 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 25

Country: Number of subjects enrolled

Czech Republic: 22

Country: Number of subjects enrolled

Estonia: 12

Country: Number of subjects enrolled

Japan: 51

Country: Number of subjects enrolled

Latvia: 9

Country: Number of subjects enrolled

Lithuania: 14

Country: Number of subjects enrolled

Poland: 29

Country: Number of subjects enrolled

Romania: 7

Country: Number of subjects enrolled

Russian Federation: 63

Country: Number of subjects enrolled

Ukraine: 28

Country: Number of subjects enrolled

Hungary: 24

Worldwide total number of subjects

284

EEA total number of subjects

142

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)

247

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 516 participants were screened out of which 290 participants were randomized in the study. Six participants from one of the sites were excluded from ITT population prior to unblinding due to data intergrity issues.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Mavrilimumab 10 milligram (mg)

Arm description

Participants received Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks.

Mavrilimumab 30 mg

Arm description

Participants received Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Mavrilimumab (CAM-3001) 30 milligram (mg) injection subcutaneously every other week for 12 weeks.

Mavrilimumab 50 mg

Arm description

Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks.

Mavrilimumab 100 mg

Arm description

Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks.

Placebo

Arm description

Participants received Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo Matched to Mavrilimumab injection subcutaneously every other week for 12 weeks.

Number of subjects in period 1	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Started	48	49	48	47	92
Completed	44	47	46	45	82
Not completed	4	2	2	2	10
Consent withdrawn by subject	-	-	-	1	3
Adverse event, non-fatal	1	-	1	-	2
Unspecified	3	2	1	1	5

Baseline characteristics

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Reporting group title

Mavrilimumab 10 milligram (mg)

Reporting group description

Reporting group title

Mavrilimumab 30 mg

Reporting group description

Reporting group title

Mavrilimumab 50 mg

Reporting group description

Reporting group title

Mavrilimumab 100 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo	Total
Number of subjects	48	49	48	47	92	284
Age categorical
Units: Subjects
Adults (18- 64 Years)	42	43	42	42	78	247
Elderly (65-84 Years)	6	6	6	5	14	37
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	52.2 ( 11.9 )	51.1 ( 12.1 )	52.7 ( 10.3 )	50.1 ( 12.1 )	52.1 ( 12.8 )	-
Gender, Male/Female
Units: participants
Female	39	43	44	40	82	248
Male	9	6	4	7	10	36

End points

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Reporting group title

Mavrilimumab 10 milligram (mg)

Reporting group description

Reporting group title

Mavrilimumab 30 mg

Reporting group description

Reporting group title

Mavrilimumab 50 mg

Reporting group description

Reporting group title

Mavrilimumab 100 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

Subject analysis set title

Mavrilimumab 50 mg

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Mavrilimumab 100mg

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

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End point title

Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

End point description

DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per Liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, greater than or equal to (>=) 3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. The intent-to-treat (ITT) population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Primary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)	37.5	63.3	47.9	68.1	32.6

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.578 ^[2]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-11.5

upper limit

Notes
[1] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[2] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

< 0.001 ^[4]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

30.7

Confidence interval

level

95%

sides

2-sided

lower limit

13.4

upper limit

46.3

Notes
[3] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[4] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.099 ^[6]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

15.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

32.2

Notes
[5] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[6] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

< 0.001 ^[8]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

35.5

Confidence interval

level

95%

sides

2-sided

lower limit

17.8

upper limit

50.6

Notes
[7] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[8] - p-value was calculated using a two-tailed Fisher’s exact test.

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

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End point title

Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

End point description

DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. DAS28 (CRP) response at Day 85 for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European Region (n=75, 39, 41, 39, 39)	41	61	51.3	66.7	34.7
Japanese Region (n=17, 9, 8, 9, 8)	22.2	75	33.3	75	23.5

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[9]

P-value

= 0.543 ^[10]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-11.9

upper limit

25.4

Notes
[9] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[10] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.011 ^[12]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

26.3

Confidence interval

level

95%

sides

2-sided

lower limit

7.2

upper limit

43.6

Notes
[11] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[12] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

= 0.108 ^[14]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

16.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

35.5

Notes
[13] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[14] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[15]

P-value

= 0.001 ^[16]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.5

upper limit

Notes
[15] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[16] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 5

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

= 1 ^[18]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-33.7

upper limit

35.7

Notes
[17] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[18] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 6

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[19]

P-value

= 0.028 ^[20]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

51.5

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

Notes
[19] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[20] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 7

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[21]

P-value

= 0.661 ^[22]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

9.8

Confidence interval

level

95%

sides

2-sided

lower limit

-24.3

upper limit

46.9

Notes
[21] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[22] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 8

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[23]

P-value

= 0.028 ^[24]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

51.5

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

Notes
[23] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[24] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

Top of page

End point title

Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

End point description

DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Primary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)	50	61.2	58.3	66	37

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[25]

P-value

= 0.152 ^[26]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

30.3

Notes
[25] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[26] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.008 ^[28]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

24.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

40.3

Notes
[27] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[28] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.02 ^[30]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

21.4

Confidence interval

level

95%

sides

2-sided

lower limit

3.9

upper limit

37.8

Notes
[29] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[30] - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[31]

P-value

= 0.002 ^[32]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

11.3

upper limit

Notes
[31] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[32] - p-value was calculated using a two-tailed Fisher’s exact test.

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

Top of page

End point title

Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

End point description

DAS28 (ESR) calculated SJC and TJC using the 28 joints,GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0=best, 10=worst),and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score=more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. DAS28 (ESR) response at Day 85 for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European Region (n=75, 39, 41, 39, 39)	51.3	58.5	61.5	64.1	41.3
Japanese Region (n=17, 9, 8, 9, 8)	44.4	75	44.4	75	17.6

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[33]

P-value

= 0.328 ^[34]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

29.4

Notes
[33] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[34] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[35]

P-value

= 0.084 ^[36]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

17.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

35.6

Notes
[35] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[36] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[37]

P-value

= 0.049 ^[38]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

20.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

38.2

Notes
[37] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[38] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[39]

P-value

= 0.03 ^[40]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

22.8

Confidence interval

level

95%

sides

2-sided

lower limit

3.2

upper limit

40.7

Notes
[39] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[40] - European region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 5

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[41]

P-value

= 0.188 ^[42]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

26.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

60.7

Notes
[41] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[42] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 6

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[43]

P-value

= 0.01 ^[44]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

57.4

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

81.8

Notes
[43] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[44] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 7

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[45]

P-value

= 0.188 ^[46]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

26.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.3

upper limit

60.7

Notes
[45] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[46] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 8

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[47]

P-value

= 0.01 ^[48]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

57.4

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

81.8

Notes
[47] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[48] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 ^[49]

End point description

DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline more than (>)1.2 but less than (<) 3.2; moderate response: change from baseline >1.2 to more than or equal to (>=) 3.2 or less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 to >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 to >5.1. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Primary

End point timeframe

Day 85

Notes
[49] - 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 done, no inferential statistical analyses were performed.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
No response	47.9	28.6	35.4	23.4	51.1
Moderate response	31.3	38.8	41.7	42.6	34.8
Good response	20.8	32.7	22.9	34	14.1

No statistical analyses for this end point

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region ^[50]

End point description

End point type

Primary

End point timeframe

Day 85

Notes
[50] - 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 done, no inferential statistical analyses were performed.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European: No response (n=75,39,41,39,39)	46.2	29.3	33.3	23.1	49.3
European: Moderate response (n=75,39,41,39,39)	33.3	41.5	41	46.2	36
European: Good response (n=75,39,41,39,39)	20.5	29.3	25.6	30.8	14.7
Japanese: No response (n=17,9,8,9,8)	55.6	25	44.4	25	58.8
Japanese: Moderate response (n=17,9,8,9,8)	22.2	25	44.4	25	29.4
Japanese: Good response (n=17,9,8,9,8)	22.2	50	11.1	50	11.8

No statistical analyses for this end point

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

Top of page

End point title

Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 ^[51]

End point description

End point type

Primary

End point timeframe

Day 85

Notes
[51] - 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 done, no inferential statistical analyses were performed.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
No response	39.6	36.7	33.3	25.5	55.4
Moderate response	45.8	44.9	54.2	53.2	35.9
Good response	14.6	18.4	12.5	21.3	8.7

No statistical analyses for this end point

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Top of page

End point title

Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region ^[52]

End point description

End point type

Primary

End point timeframe

Day 85

Notes
[52] - 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 done, no inferential statistical analyses were performed.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European: No response (n=75,39,41,39,39)	38.5	39	33.3	28.2	53.3
European: Moderate response (n=75,39,41,39,39)	46.2	43.9	53.8	51.3	38.7
European: Good response (n=75,39,41,39,39)	15.4	17.1	12.8	20.5	8
Japanese: No response (n=17,9,8,9,8)	44.4	25	33.3	12.5	64.7
Japanese: Moderate response (n=17,9,8,9,8)	44.4	50	55.6	62.5	23.5
Japanese: Good response (n=17,9,8,9,8)	11.1	25	11.1	25	11.8

No statistical analyses for this end point

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Top of page

End point title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) ^[53] ^[54]

End point description

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up Day 169 that were absent before treatment or that worsened relative to pretreatment state. The safety population included all participants who received any dose of investigational product.

End point type

Primary

End point timeframe

Baseline up to Day 169 (follow-up)

Notes
[53] - 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 done, no inferential statistical analyses were performed.
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: participants
TEAEs	33	31	46	26	28
TESAEs	2	2	1	1	0

No statistical analyses for this end point

Primary: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

Top of page

End point title

Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) ^[55] ^[56]

End point description

Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported. The safety population included all participants who received any dose of investigational product.

End point type

Primary

End point timeframe

Baseline up to Day 169 (follow-up)

Notes
[55] - 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 done, no inferential statistical analyses were performed.
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: participants
Pyrexia	0	0	1	2	0
Hypertension	0	1	2	0	0

No statistical analyses for this end point

Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Results

Top of page

End point title

Number of Participants With Abnormal Electrocardiogram (ECG) Results ^[57] ^[58]

End point description

12-lead ECG was recorded and corrected QT (QTc) interval was measured with the participant in a rested supine position for at least 10 minutes. Any ECG abnormality deemed clinically significant as per investigator’s discretion were reported. The safety population included all participants who received any dose of investigational product.

End point type

Primary

End point timeframe

Baseline up to Day 169 (follow-up)

Notes
[57] - 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 done, no inferential statistical analyses were performed.
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: participants	1	0	0	0	2

No statistical analyses for this end point

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Top of page

End point title

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 ^[59] ^[60]

End point description

FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure.

End point type

Primary

End point timeframe

Day 85

Notes
[59] - 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 done, no inferential statistical analyses were performed.
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	46	47	47	87	49
Units: liters
arithmetic mean (standard deviation)
FEV1	2.877 ( 0.821 )	2.949 ( 0.722 )	2.793 ( 0.69 )	2.73 ( 0.764 )	2.701 ( 0.489 )
FVC	3.582 ( 0.967 )	3.667 ( 0.882 )	3.499 ( 0.766 )	3.439 ( 0.949 )	3.37 ( 0.527 )

No statistical analyses for this end point

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

Top of page

End point title

Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region ^[61] ^[62]

End point description

FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC at Day 85 for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for the specified region for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

Notes
[61] - 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 done, no inferential statistical analyses were performed.
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	46	47	47	87	49
Units: liters
arithmetic mean (standard deviation)
European: FEV1 (n=71,37,39,40,39)	2.902 ( 0.81 )	3.042 ( 0.745 )	2.848 ( 0.699 )	2.811 ( 0.79 )	2.698 ( 0.501 )
European: FVC (n=71,37,39,40,39)	3.632 ( 0.948 )	3.779 ( 0.917 )	3.553 ( 0.772 )	3.537 ( 0.996 )	3.355 ( 0.537 )
Japanese: FEV1 (n=16,9,8,9,8)	2.774 ( 0.908 )	2.493 ( 0.354 )	2.52 ( 0.616 )	2.367 ( 0.51 )	2.712 ( 0.457 )
Japanese: FVC (n=16,9,8,9,8)	3.378 ( 1.076 )	3.119 ( 0.37 )	3.235 ( 0.725 )	3.005 ( 0.534 )	3.434 ( 0.505 )

No statistical analyses for this end point

Primary: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Top of page

End point title

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 ^[63] ^[64]

End point description

FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.

End point type

Primary

End point timeframe

Baseline and Day 85

Notes
[63] - 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 done, no inferential statistical analyses were performed.
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: liters
arithmetic mean (standard deviation)
Baseline: FEV1 (n=87,43,45,49,48)	2.788 ( 0.773 )	2.99 ( 0.765 )	2.79 ( 0.77 )	2.76 ( 0.43 )	2.831 ( 0.681 )
Change at Day 85: FEV1 (n=87,46,47,49,47)	0.044 ( 0.231 )	0.016 ( 0.196 )	-0.039 ( 0.234 )	-0.059 ( 0.249 )	-0.049 ( 0.221 )
Baseline: FVC (n=87,43,45,49,48)	3.486 ( 0.963 )	3.759 ( 0.868 )	3.456 ( 0.948 )	3.409 ( 0.496 )	3.506 ( 0.804 )
Change at Day 85: FVC (n=87,46,47,49,47)	0.048 ( 0.243 )	-0.013 ( 0.239 )	-0.012 ( 0.301 )	-0.039 ( 0.496 )	-0.017 ( 0.218 )

No statistical analyses for this end point

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Top of page

End point title

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 ^[65] ^[66]

End point description

DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

End point type

Primary

End point timeframe

Day 85

Notes
[65] - 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 done, no inferential statistical analyses were performed.
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	46	47	47	87	49
Units: percent diffusion capacity
arithmetic mean (standard deviation)	95 ( 16.2 )	95 ( 15.1 )	89.3 ( 12 )	91.7 ( 16.7 )	95 ( 15.7 )

No statistical analyses for this end point

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

Top of page

End point title

Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region ^[67] ^[68]

End point description

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

Notes
[67] - 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 done, no inferential statistical analyses were performed.
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	46	47	47	87	49
Units: percent diffusion capacity
arithmetic mean (standard deviation)
European region: (n=71,37,39,40,39)	96 ( 16.9 )	94 ( 15.2 )	88.6 ( 10.7 )	90.4 ( 16.5 )	94.8 ( 16.5 )
Japanese region (n=16,9,8,9,8)	91 ( 13.3 )	100.1 ( 14.6 )	93 ( 17.2 )	97.6 ( 16.9 )	96 ( 12.6 )

No statistical analyses for this end point

Primary: Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Top of page

End point title

Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 ^[69] ^[70]

End point description

DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.

End point type

Primary

End point timeframe

Baseline and Day 85

Notes
[69] - 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 done, no inferential statistical analyses were performed.
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: percent diffusion capacity
arithmetic mean (standard deviation)
Baseline (n=86,40,45,49,48)	96.3 ( 17.7 )	93.7 ( 15.5 )	91.5 ( 12.5 )	97.5 ( 14.8 )	92.5 ( 13.7 )
Change at Day 85 (n=87,46,47,49,47)	-3.1 ( 17.3 )	0.4 ( 11.1 )	0.1 ( 14.3 )	-2.5 ( 10.8 )	-3.7 ( 11.3 )

No statistical analyses for this end point

Primary: Dyspnea Score at Day 85

Top of page

End point title

Dyspnea Score at Day 85 ^[71] ^[72]

End point description

End point type

Primary

End point timeframe

Day 85

Notes
[71] - 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 done, no inferential statistical analyses were performed.
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	45	47	47	89	49
Units: units on a scale
arithmetic mean (standard deviation)	0.13 ( 0.38 )	0.35 ( 0.7 )	0.35 ( 0.59 )	0.25 ( 0.48 )	0.15 ( 0.44 )

No statistical analyses for this end point

Primary: Change from Baseline in Dyspnea Score at Day 85

Top of page

End point title

Change from Baseline in Dyspnea Score at Day 85 ^[73] ^[74]

End point description

Modified Borg dyspnea scale is a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

End point type

Primary

End point timeframe

Baseline and Day 85

Notes
[73] - 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 done, no inferential statistical analyses were performed.
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=96,48,49,49,48)	0.26 ( 0.88 )	0.26 ( 0.59 )	0.29 ( 0.58 )	0.19 ( 0.49 )	0.32 ( 0.59 )
Change at Day 85 (n=89,45,47,49,47)	-0.14 ( 0.62 )	0.1 ( 0.44 )	-0.06 ( 0.53 )	-0.04 ( 0.35 )	0.02 ( 0.56 )

No statistical analyses for this end point

Primary: Categorized Dyspnea Score at Day 85

Top of page

End point title

Categorized Dyspnea Score at Day 85 ^[75] ^[76]

End point description

Modified Borg dyspnea scale is a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The modified BORG dyspnea scale was categorized as - no/slight (0 to 2), moderate (3 and 4), severe (5 and 6) and very severe breathlessness (7 and above). The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

Notes
[75] - 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 done, no inferential statistical analyses were performed.
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	45	47	47	89	49
Units: participants
No/Slight breathlessness	45	45	46	89	49
Moderate breathlessness	0	2	1	0	0
Severe breathlessness	0	0	0	0	0
Very severe breathlessness	0	0	0	0	0

No statistical analyses for this end point

Primary: Oxygen Saturation Level at Day 85

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End point title

Oxygen Saturation Level at Day 85 ^[77] ^[78]

End point description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

End point type

Primary

End point timeframe

Day 85

Notes
[77] - 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 done, no inferential statistical analyses were performed.
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	45	47	47	88	49
Units: percent saturation
arithmetic mean (standard deviation)	97.6 ( 1.3 )	97.7 ( 1.3 )	97.3 ( 1.5 )	97.5 ( 1.2 )	97.2 ( 1.8 )

No statistical analyses for this end point

Primary: Oxygen Saturation Level at Day 85 by Region

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End point title

Oxygen Saturation Level at Day 85 by Region ^[79] ^[80]

End point description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Primary

End point timeframe

Day 85

Notes
[79] - 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 done, no inferential statistical analyses were performed.
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Placebo	Mavrilimumab 50 mg
Number of subjects analysed	45	47	47	88	49
Units: percent saturation
arithmetic mean (standard deviation)
European region: (n=72,36,39,40,39)	97.6 ( 1.3 )	97.6 ( 1.3 )	97.3 ( 1.6 )	97.5 ( 1.3 )	97.2 ( 2 )
Japanese region: (n=16,9,8,9,8)	97.4 ( 1 )	98.4 ( 1.1 )	97.3 ( 1.3 )	97.6 ( 0.9 )	97.4 ( 0.7 )

No statistical analyses for this end point

Primary: Change from Baseline in Oxygen Saturation Level at Day 85

Top of page

End point title

Change from Baseline in Oxygen Saturation Level at Day 85 ^[81] ^[82]

End point description

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.

End point type

Primary

End point timeframe

Baseline and Day 85

Notes
[81] - 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 done, no inferential statistical analyses were performed.
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: percent saturation
arithmetic mean (standard deviation)
Baseline (n=96,48,49,49,48)	97.8 ( 1.6 )	97.6 ( 1.2 )	97.5 ( 1.3 )	97.6 ( 1.4 )	97.2 ( 1.7 )
Change at Day 85 (n=88,45,47,49,47)	-0.2 ( 1.5 )	0.1 ( 1.4 )	0 ( 1.5 )	-0.3 ( 1.9 )	0.1 ( 2.1 )

No statistical analyses for this end point

Primary: Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

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End point title

Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) ^[83] ^[84]

End point description

Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, reticulocytes, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration); serum chemistry (creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamyl transferase, CRP, ESR, albumin, total cholesterol, triglycerides, rheumatoid factor and anti-cyclic citrullinated peptide antibodies); urinalysis (albumin, glucose, protein, blood, nitrite). The safety population included all participants who received any dose of investigational product.

End point type

Primary

End point timeframe

Baseline up to Day 169 (follow-up)

Notes
[83] - 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 done, no inferential statistical analyses were performed.
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Placebo	Mavrilimumab 50 mg	Mavrilimumab 100mg
Number of subjects analysed	48	49	96	49	48
Units: participants
Blood and lymphatic system disorders	3	3	10	3	4
Hepatic abnormality	5	3	3	2	3
Blood cholesterol increased	0	0	0	1	0
Blood triglycerides increased	0	0	1	0	0
Hypercholesterolemia	1	1	1	1	0
Hyperglycemia	0	0	1	1	0
Urinalysis abnormalities	0	3	3	1	0

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

Top of page

End point title

Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

End point description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline and Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: units on a scale
arithmetic mean (standard error)
DAS28(CRP): Baseline (n=92,48,49,48,47)	5.24 ( 0.16 )	5.42 ( 0.139 )	5.14 ( 0.146 )	5.34 ( 0.115 )	5.43 ( 0.11 )
DAS28(CRP): Change at Day 85 (n=84,45,46,48,46)	-1.27 ( 0.166 )	-1.63 ( 0.163 )	-1.32 ( 0.162 )	-1.7 ( 0.165 )	-0.97 ( 0.12 )
DAS28(ESR): Baseline: (n=92,48,49,48,47)	6.06 ( 0.165 )	6.31 ( 0.145 )	5.98 ( 0.163 )	6.06 ( 0.119 )	6.18 ( 0.118 )
DAS28(ESR): Change at Day 85 (n=85,45,47,48,46)	-1.39 ( 0.172 )	-1.8 ( 0.17 )	-1.46 ( 0.168 )	-1.84 ( 0.172 )	-1.04 ( 0.125 )

Statistical Analysis 1

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[85]

P-value

= 0.137

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.205

Notes
[85] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[86]

P-value

= 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.202

Notes
[86] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[87]

P-value

= 0.08

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.201

Notes
[87] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[88]

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.204

Notes
[88] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 5

Statistical analysis description

Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[89]

P-value

= 0.107

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.08

Variability estimate

Standard error of the mean

Dispersion value

0.212

Notes
[89] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 6

Statistical analysis description

Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[90]

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.17

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.21

Notes
[90] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 7

Statistical analysis description

Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[91]

P-value

= 0.046

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.209

Notes
[91] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 8

Statistical analysis description

Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[92]

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

-0.38

Variability estimate

Standard error of the mean

Dispersion value

0.212

Notes
[92] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

Top of page

End point title

Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

End point description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline and Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: units on a scale
arithmetic mean (standard error)
European: DAS28(CRP): Baseline (n=75,39,41,39,39)	5.3 ( 0.172 )	5.48 ( 0.154 )	5.33 ( 0.155 )	5.41 ( 0.111 )	5.58 ( 0.117 )
European: DAS28(CRP): Day 85 (n=68,36,38,39,38)	-1.4 ( 0.187 )	-1.55 ( 0.181 )	-1.43 ( 0.181 )	-1.7 ( 0.183 )	-1 ( 0.133 )
Japanese: DAS28(CRP): Baseline (n=17,9,8,9,8)	5 ( 0.427 )	5.12 ( 0.306 )	4.32 ( 0.268 )	5.04 ( 0.413 )	4.75 ( 0.242 )
Japanese: DAS28(CRP): Day 85 (n=16,9,8,9,8)	-0.73 ( 0.358 )	-2.04 ( 0.381 )	-0.89 ( 0.361 )	-1.71 ( 0.38 )	-0.85 ( 0.281 )
European: DAS28(ESR): Baseline (n=75,39,41,39,39)	6.1 ( 0.18 )	6.36 ( 0.163 )	6.23 ( 0.159 )	6.12 ( 0.118 )	6.36 ( 0.124 )
European: DAS28(ESR): Day 85 (n=69,36,39,39,38)	-1.51 ( 0.196 )	-1.76 ( 0.19 )	-1.53 ( 0.19 )	-1.85 ( 0.193 )	-1.12 ( 0.14 )
Japanese: DAS28(ESR): Baseline (n=17,9,8,9,8)	5.87 ( 0.426 )	6.05 ( 0.309 )	4.93 ( 0.379 )	5.78 ( 0.404 )	5.38 ( 0.248 )
Japanese: DAS28(ESR): Day 85 (n=16,9,8,9,8)	-0.83 ( 0.359 )	-1.99 ( 0.382 )	-1.24 ( 0.362 )	-1.78 ( 0.38 )	-0.74 ( 0.276 )

Statistical Analysis 1

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[93]

P-value

= 0.086

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.23

Notes
[93] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[94]

P-value

= 0.016

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.225

Notes
[94] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[95]

P-value

= 0.059

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.225

Notes
[95] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[96]

P-value

= 0.002

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.227

Notes
[96] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 5

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[97]

P-value

= 0.107

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.241

Notes
[97] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 6

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[98]

P-value

= 0.007

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.236

Notes
[98] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 7

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[99]

P-value

= 0.084

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.236

Notes
[99] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 8

Statistical analysis description

European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[100]

P-value

= 0.002

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.238

Notes
[100] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 9

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[101]

P-value

= 0.785

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

1.02

Variability estimate

Standard error of the mean

Dispersion value

0.447

Notes
[101] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 10

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[102]

P-value

= 0.014

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.19

Confidence interval

level

95%

sides

2-sided

lower limit

-2.13

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.465

Notes
[102] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 11

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[103]

P-value

= 0.931

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

0.86

Variability estimate

Standard error of the mean

Dispersion value

0.448

Notes
[103] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 12

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[104]

P-value

= 0.07

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.07

Variability estimate

Standard error of the mean

Dispersion value

0.465

Notes
[104] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 13

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[105]

P-value

= 0.854

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.449

Notes
[105] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 14

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[106]

P-value

= 0.011

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.25

Confidence interval

level

95%

sides

2-sided

lower limit

-2.19

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.468

Notes
[106] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 15

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[107]

P-value

= 0.271

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.448

Notes
[107] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 16

Statistical analysis description

Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[108]

P-value

= 0.031

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.97

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.465

Notes
[108] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

End point description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
DAS28(CRP)	14.6	22.4	18.8	23.4	7.6
DAS28(ESR)	6.3	8.2	8.3	6.4	3.3

Statistical Analysis 1

Statistical analysis description

DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[109]

P-value

= 0.238

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

20.5

Notes
[109] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[110]

P-value

= 0.017

Method

Fisher exact

Parameter type

Percent difference

Point estimate

14.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

29.7

Notes
[110] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[111]

P-value

= 0.09

Method

Fisher exact

Parameter type

Percent difference

Point estimate

11.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

25.4

Notes
[111] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[112]

P-value

= 0.015

Method

Fisher exact

Parameter type

Percent difference

Point estimate

15.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.9

upper limit

Notes
[112] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 5

Statistical analysis description

DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[113]

P-value

= 0.412

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

Notes
[113] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 6

Statistical analysis description

DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[114]

P-value

= 0.237

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

16.4

Notes
[114] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 7

Statistical analysis description

DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[115]

P-value

= 0.231

Method

Fisher exact

Parameter type

Percent difference

Point estimate

5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

16.8

Notes
[115] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Statistical Analysis 8

Statistical analysis description

DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[116]

P-value

= 0.406

Method

Fisher exact

Parameter type

Percent difference

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

14.4

Notes
[116] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

End point description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European: DAS28(CRP):(n=75,39,41,39,39)	15.4	17.1	17.9	23.1	6.7
European: DAS28(ESR):(n=75,39,41,39,39)	7.7	9.8	7.7	7.7	1.3
Japanese: DAS28(CRP) (n=17,9,8,9,8)	11.1	50	22.2	25	11.8
Japanese: DAS28(ESR) (n=17,9,8,9,8)	0	0	11.1	0	11.8

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[117]

P-value

= 0.182 ^[118]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

24.4

Notes
[117] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[118] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[119]

P-value

= 0.11 ^[120]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

10.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

25.5

Notes
[119] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[120] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[121]

P-value

= 0.104 ^[122]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

11.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

26.9

Notes
[121] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[122] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[123]

P-value

= 0.016 ^[124]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

16.4

Confidence interval

level

95%

sides

2-sided

lower limit

3.5

upper limit

32.7

Notes
[123] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[124] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 5

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

other ^[125]

P-value

= 0.115 ^[126]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

19.3

Notes
[125] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[126] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 6

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[127]

P-value

= 0.052 ^[128]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

8.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

21.6

Notes
[127] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[128] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 7

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

other ^[129]

P-value

= 0.115 ^[130]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

19.3

Notes
[129] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[130] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 8

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

235

Analysis specification

Pre-specified

Analysis type

other ^[131]

P-value

= 0.115 ^[132]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

19.3

Notes
[131] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[132] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 9

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[133]

P-value

= 1 ^[134]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-27

upper limit

34.8

Notes
[133] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[134] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 10

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[135]

P-value

= 0.059 ^[136]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

38.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

71.2

Notes
[135] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[136] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 11

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[137]

P-value

= 0.591 ^[138]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-18.2

upper limit

46.2

Notes
[137] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[138] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 12

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[139]

P-value

= 0.57 ^[140]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-16.6

upper limit

51.4

Notes
[139] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[140] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 13

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[141]

P-value

= 0.529 ^[142]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

22.7

Notes
[141] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[142] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 14

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[143]

P-value

= 1 ^[144]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-37.5

upper limit

22.6

Notes
[143] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[144] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 15

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[145]

P-value

= 1 ^[146]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-27

upper limit

34.8

Notes
[145] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[146] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 16

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[147]

P-value

= 1 ^[148]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-37.5

upper limit

22.6

Notes
[147] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
[148] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

Top of page

End point title

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

End point description

DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Secondary

End point timeframe

Baseline up to Day 169 (follow-up)

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: days
median (confidence interval 95%)
DAS28 (CRP) Response	84 (43 to 99999)	43 (29 to 58)	71 (42 to 89)	42 (29 to 45)	88 (57 to 88)
DAS28 (CRP) Remission	99999 (-99999 to 99999)	99999 (99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)
DAS28 (ESR) Response	58 (43 to 86)	30 (29 to 43)	57 (29 to 71)	29 (28 to 42)	85 (57 to 88)
DAS28 (ESR) Remission	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

Statistical Analysis 1

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.604

Method

Logrank

Confidence interval

Statistical Analysis 2

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 3

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.145

Method

Logrank

Confidence interval

Statistical Analysis 4

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 5

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.282

Method

Logrank

Confidence interval

Statistical Analysis 6

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 7

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.047

Method

Logrank

Confidence interval

Statistical Analysis 8

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

Top of page

End point title

Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

End point description

DAS28 calculated SJC and TJC using the 28 joints,GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0=best,10=worst) and CRP(mg/L) for DAS28(CRP)orESR(mm/hour) for DAS28(ESR). Total score range:0-9.4, higher score=more disease activity.DAS28<3.2=low disease activity,>=3.2 to 5.1=moderate to high disease activity and<2.6=remission.Response was defined as 1.2 decrease from baseline in DAS28(CRP)orDAS28(ESR) score. Remission was defined as <2.6 DAS28(CRP)orDAS28(ESR) score. Time to response for DAS28(CRP) and DAS28(ESR) by region were reported. Time to remission for DAS28(CRP) and DAS28(ESR) by region were not analyzed because time to remission for the overall study population could not be achieved. The ITT population was analysed and six participants were excluded for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline up to Day 169 (follow-up)

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: days
median (confidence interval 95%)
European: DAS28 (CRP) Response (n=75,39,41,39,39)	43 (43 to 99999)	43 (42 to 71)	50 (29 to 89)	42 (29 to 57)	85 (57 to 88)
Japanese: DAS28 (CRP) Response (n=17,9,8,9,8)	99999 (-99999 to 99999)	22.5 (15 to 57)	87 (30 to 87)	37 (15 to 57)	99999 (-99999 to 99999)
European: DAS28 (ESR) Response (n=75,39,41,39,39)	57 (30 to 85)	42 (29 to 43)	52.5 (29 to 84)	29 (28 to 42)	71 (57 to 88)
Japanese: DAS28 (ESR) Response (n=17,9,8,9,8)	86 (57 to 86)	29 (15 to 44)	44.5 (29 to 99999)	30 (15 to 44)	99999 (-99999 to 99999)

Statistical Analysis 1

Statistical analysis description

European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.237

Method

Logrank

Confidence interval

Statistical Analysis 2

Statistical analysis description

European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Logrank

Confidence interval

Statistical Analysis 3

Statistical analysis description

European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.134

Method

Logrank

Confidence interval

Statistical Analysis 5

Statistical analysis description

Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.265

Method

Logrank

Confidence interval

Statistical Analysis 4

Statistical analysis description

European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 6

Statistical analysis description

Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.013

Method

Logrank

Confidence interval

Statistical Analysis 7

Statistical analysis description

Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.952

Method

Logrank

Confidence interval

Statistical Analysis 9

Statistical analysis description

European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.246

Method

Logrank

Confidence interval

Statistical Analysis 10

Statistical analysis description

European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 8

Statistical analysis description

Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004

Method

Logrank

Confidence interval

Statistical Analysis 11

Statistical analysis description

European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.126

Method

Logrank

Confidence interval

Statistical Analysis 12

Statistical analysis description

European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Statistical Analysis 15

Statistical analysis description

Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.125

Method

Logrank

Confidence interval

Statistical Analysis 14

Statistical analysis description

Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Logrank

Confidence interval

Statistical Analysis 13

Statistical analysis description

Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.831

Method

Logrank

Confidence interval

Statistical Analysis 16

Statistical analysis description

Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Logrank

Confidence interval

Secondary: Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

Top of page

End point title

Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

End point description

DAS28 calculated SJC and TJC using 28 joints,GH using participant assessment of disease activity(participant rated arthritis activity using numerical rating scale with 0=best,10=worst) andCRP(mg/L)for DAS28(CRP)or ESR(mm/hour) for DAS28(ESR).Total score range:0-9.4,higher score=more disease activity.DAS28<3.2=low disease activity,>=3.2 to 5.1=moderate to high disease activity and<2.6=remission.Response defined as 1.2 decrease from baseline in DAS28(CRP)or DAS28(ESR)score.Remission defined as<2.6 DAS28(CRP)orDAS28(ESR)score.Expected duration of response(DOR) calculated as response rate(in percentage) multiplied by mean DOR(in days) by using Weibull Model.Duration of DAS28(CRP)andDAS28(ESR) remission were not analyzed because very few participants achieved remission in the overall study population.ITT population (6 participants were excluded for data integrity issues).Here "n" signifies participants who were evaluable for this measure for specified parameter for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline up to Day 169

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: Percentage of days
number (not applicable)
DAS28 (CRP) Response	42.19	81.89	54.8	83.07	43.4
DAS28 (ESR) Response	52.96	71.14	75.97	96.52	46.11

Statistical Analysis 1

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[149]

P-value

= 0.486

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.69

Notes
[149] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[150]

P-value

= 0.015

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

2.18

Notes
[150] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[151]

P-value

= 0.006

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

2.36

Notes
[151] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[152]

P-value

< 0.001

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

2.09

Confidence interval

level

95%

sides

2-sided

lower limit

1.49

upper limit

2.93

Notes
[152] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 5

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[153]

P-value

= 0.906

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.55

Notes
[153] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 6

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[154]

P-value

< 0.001

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

2.71

Notes
[154] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 7

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[155]

P-value

= 0.272

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.91

Notes
[155] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 8

Statistical analysis description

Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[156]

P-value

< 0.001

Method

Exponential,Weibull and Log normal model

Parameter type

Ratio of expected duration of response

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

2.72

Notes
[156] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

Top of page

End point title

Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

End point description

ACR20, ACR50, and ACR70, were defined as greater than or equal to (>=) 20 percent (%),>=50%, or >=70% improvement, respectively, in: swollen joint count and tender joint count and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
ACR20	41.7	57.1	37.5	70.2	37
ACR50	20.8	30.6	16.7	34	12
ACR70	4.2	10.2	6.3	14.9	5.4

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[157]

P-value

= 0.589 ^[158]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

Notes
[157] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[158] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[159]

P-value

= 0.032 ^[160]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

20.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

36.7

Notes
[159] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[160] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[161]

P-value

= 1 ^[162]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

Notes
[161] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[162] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[163]

P-value

< 0.001 ^[164]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

33.3

Confidence interval

level

95%

sides

2-sided

lower limit

15.6

upper limit

48.6

Notes
[163] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[164] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-

Statistical Analysis 5

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[165]

P-value

= 0.212 ^[166]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

23.6

Notes
[165] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[166] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 6

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[167]

P-value

= 0.011 ^[168]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

18.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.8

upper limit

Notes
[167] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[168] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 7

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[169]

P-value

= 0.446 ^[170]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

19.1

Notes
[169] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[170] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 8

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[171]

P-value

= 0.003 ^[172]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

22.1

Confidence interval

level

95%

sides

2-sided

lower limit

7.6

upper limit

37.8

Notes
[171] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[172] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 9

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[173]

P-value

= 1 ^[174]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.9

upper limit

9.7

Notes
[173] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[174] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 10

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[175]

P-value

= 0.317 ^[176]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

17.5

Notes
[175] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[176] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 11

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[177]

P-value

= 1 ^[178]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

12.1

Notes
[177] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[178] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 12

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[179]

P-value

= 0.106 ^[180]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

9.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

23.5

Notes
[179] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[180] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

Top of page

End point title

Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

End point description

ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Data for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: percentage of participants
number (not applicable)
European: ACR20 (n=75,39,41,39,39)	41	56.1	41	69.2	40
Japanese: ACR20 (n=17,9,8,9,8)	44.4	62.5	22.2	75	23.5
European: ACR50 (n=75,39,41,39,39)	23.1	29.3	20.5	30.8	12
Japanese: ACR50 (n=17,9,8,9,8)	11.1	37.5	0	50	11.8
European: ACR70 (n=75,39,41,39,39)	5.1	9.8	7.7	17.9	4
Japanese: ACR70 (n=17,9,8,9,8)	0	12.5	0	0	11.8

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[181]

P-value

= 1 ^[182]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

20.4

Notes
[181] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[182] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[183]

P-value

= 0.12 ^[184]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

16.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

34.4

Notes
[183] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
[184] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[185]

P-value

= 1 ^[186]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

20.4

Notes
[185] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[186] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[187]

P-value

= 0.005 ^[188]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

29.2

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

46.1

Notes
[187] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[188] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 5

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[189]

P-value

= 0.382 ^[190]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

20.9

Confidence interval

level

95%

sides

2-sided

lower limit

-16.4

upper limit

55.9

Notes
[189] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
[190] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 6

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[191]

P-value

= 0.087 ^[192]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

69.6

Notes
[191] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[192] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 7

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[193]

P-value

= 1 ^[194]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-33.7

upper limit

35.7

Notes
[193] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
[194] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 8

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[195]

P-value

= 0.028 ^[196]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

51.5

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

Notes
[195] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[196] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 9

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[197]

P-value

= 0.175 ^[198]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

11.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

27.9

Notes
[197] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[198] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 11

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[199]

P-value

= 0.271 ^[200]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

24.9

Notes
[199] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[200] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 10

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[201]

P-value

= 0.026 ^[202]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

17.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

34.1

Notes
[201] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[202] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 12

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[203]

P-value

= 0.021 ^[204]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

18.8

Confidence interval

level

95%

sides

2-sided

lower limit

3.4

upper limit

Notes
[203] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[204] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 14

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[205]

P-value

= 0.283 ^[206]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

25.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

63.2

Notes
[205] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[206] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 13

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[207]

P-value

= 1 ^[208]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-27

upper limit

34.8

Notes
[207] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[208] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 15

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[209]

P-value

= 0.529 ^[210]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

22.7

Notes
[209] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[210] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 16

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[211]

P-value

= 0.059 ^[212]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

38.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

71.2

Notes
[211] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[212] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 17

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[213]

P-value

= 1 ^[214]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

14.2

Notes
[213] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[214] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 18

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[215]

P-value

= 0.242 ^[216]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

19.4

Notes
[215] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[216] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 19

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

other ^[217]

P-value

= 0.41 ^[218]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

16.9

Notes
[217] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[218] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 20

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[219]

P-value

= 0.03 ^[220]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

13.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

29.5

Notes
[219] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[220] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 21

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[221]

P-value

= 0.529 ^[222]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

22.7

Notes
[221] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[222] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 22

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

other ^[223]

P-value

= 1 ^[224]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-26.7

upper limit

39.5

Notes
[223] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[224] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 23

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg

Number of subjects included in analysis

188

Analysis specification

Pre-specified

Analysis type

other ^[225]

P-value

= 0.529 ^[226]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

22.7

Notes
[225] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[226] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Statistical Analysis 24

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

other ^[227]

P-value

= 1 ^[228]

Method

Fisher exact

Parameter type

Percent difference

Point estimate

-11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-37.5

upper limit

22.6

Notes
[227] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
[228] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

Secondary: Number of Participants who Achieved ACR Categorical Responses

Top of page

End point title

Number of Participants who Achieved ACR Categorical Responses

End point description

ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. ACR responses were categorized as "No response", "ACR20 but not ACR50", "ACR50 but not ACR70", and "ACR70". The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	48	49	48	47	92
Units: participants
No response	28	21	30	14	58
ACR20 but not ACR50	10	13	10	17	23
ACR50 but not ACR70	8	10	5	9	6
ACR70	2	5	3	7	5

No statistical analyses for this end point

Secondary: Continuous ACR (ACRn) Score

Top of page

End point title

Continuous ACR (ACRn) Score

End point description

ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	44	47	45	46	84
Units: units on a scale
arithmetic mean (standard error)	19.13 ( 5.818 )	26.31 ( 5.652 )	12.17 ( 5.786 )	37.11 ( 5.723 )	5.09 ( 4.23 )

Statistical Analysis 1

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[229]

P-value

= 0.051

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

14.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

28.15

Variability estimate

Standard error of the mean

Dispersion value

7.162

Notes
[229] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

131

Analysis specification

Pre-specified

Analysis type

other ^[230]

P-value

= 0.003

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

21.23

Confidence interval

level

95%

sides

2-sided

lower limit

7.39

upper limit

35.07

Variability estimate

Standard error of the mean

Dispersion value

7.028

Notes
[230] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other ^[231]

P-value

= 0.322

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

7.09

Confidence interval

level

95%

sides

2-sided

lower limit

-6.96

upper limit

21.14

Variability estimate

Standard error of the mean

Dispersion value

7.136

Notes
[231] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[232]

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

32.03

Confidence interval

level

95%

sides

2-sided

lower limit

18.08

upper limit

45.98

Variability estimate

Standard error of the mean

Dispersion value

7.085

Notes
[232] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Secondary: Continuous ACR (ACRn) Score by Region

Top of page

End point title

Continuous ACR (ACRn) Score by Region

End point description

ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. Data for European and Japanese regions were reported. The ITT population (Six participants were excluded from the ITT population for data integrity issues). Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.

End point type

Secondary

End point timeframe

Day 85

End point values	Mavrilimumab 10 milligram (mg)	Mavrilimumab 30 mg	Mavrilimumab 50 mg	Mavrilimumab 100 mg	Placebo
Number of subjects analysed	44	47	45	46	84
Units: units on a scale
arithmetic mean (standard error)
European region (n=69,36,39,38,38)	19.18 ( 6.489 )	24.12 ( 6.263 )	12.53 ( 6.356 )	36.06 ( 6.356 )	4.71 ( 4.689 )
Japanese region (n=15,8,8,7,8)	18.09 ( 13.843 )	37.22 ( 13.843 )	10.2 ( 14.799 )	42.09 ( 13.843 )	5.99 ( 10.06 )

Statistical Analysis 1

Statistical analysis description

Analysis reported for European region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[233]

P-value

= 0.071

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

14.49

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

30.22

Variability estimate

Standard error of the mean

Dispersion value

7.981

Notes
[233] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 2

Statistical analysis description

Analysis reported for European region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

131

Analysis specification

Pre-specified

Analysis type

other ^[234]

P-value

= 0.013

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

19.43

Confidence interval

level

95%

sides

2-sided

lower limit

4.06

upper limit

34.8

Variability estimate

Standard error of the mean

Dispersion value

7.798

Notes
[234] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 3

Statistical analysis description

Analysis reported for European region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other ^[235]

P-value

= 0.32

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

7.84

Confidence interval

level

95%

sides

2-sided

lower limit

-7.68

upper limit

23.36

Variability estimate

Standard error of the mean

Dispersion value

7.873

Notes
[235] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 4

Statistical analysis description

Analysis reported for European region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[236]

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

31.37

Confidence interval

level

95%

sides

2-sided

lower limit

15.85

upper limit

46.89

Variability estimate

Standard error of the mean

Dispersion value

7.873

Notes
[236] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 5

Statistical analysis description

Analysis reported for Japanese region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 10 milligram (mg)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other ^[237]

P-value

= 0.483

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

12.11

Confidence interval

level

95%

sides

2-sided

lower limit

-22.41

upper limit

46.64

Variability estimate

Standard error of the mean

Dispersion value

17.089

Notes
[237] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 6

Statistical analysis description

Analysis reported for Japanese region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

131

Analysis specification

Pre-specified

Analysis type

other ^[238]

P-value

= 0.075

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

31.24

Confidence interval

level

95%

sides

2-sided

lower limit

-3.28

upper limit

65.77

Variability estimate

Standard error of the mean

Dispersion value

17.089

Notes
[238] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 7

Statistical analysis description

Analysis reported for Japanese region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 50 mg

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other ^[239]

P-value

= 0.815

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

4.22

Confidence interval

level

95%

sides

2-sided

lower limit

-31.89

upper limit

40.32

Variability estimate

Standard error of the mean

Dispersion value

17.872

Notes
[239] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

Statistical Analysis 8

Statistical analysis description

Analysis reported for Japanese region. Analysis Type used was dose escalation.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

other ^[240]

P-value

= 0.041

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

36.11

Confidence interval

level

95%

sides

2-sided

lower limit

1.58

upper limit

70.63

Variability estimate

Standard error of the mean

Dispersion value

17.089

Notes
[240] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

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Clinical trials

Clinical Trial Results: A Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of CAM-3001 in participants with rheumatoid arthritis (RA).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

Primary: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Results

Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Results

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

Primary: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Primary: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

Primary: Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Primary: Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

Primary: Dyspnea Score at Day 85

Primary: Dyspnea Score at Day 85

Primary: Change from Baseline in Dyspnea Score at Day 85

Primary: Change from Baseline in Dyspnea Score at Day 85

Primary: Categorized Dyspnea Score at Day 85

Primary: Categorized Dyspnea Score at Day 85

Primary: Oxygen Saturation Level at Day 85

Primary: Oxygen Saturation Level at Day 85

Primary: Oxygen Saturation Level at Day 85 by Region

Primary: Oxygen Saturation Level at Day 85 by Region

Primary: Change from Baseline in Oxygen Saturation Level at Day 85

Primary: Change from Baseline in Oxygen Saturation Level at Day 85

Primary: Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

Primary: Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

Secondary: Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

Secondary: Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

Secondary: Number of Participants who Achieved ACR Categorical Responses

Secondary: Number of Participants who Achieved ACR Categorical Responses

Secondary: Continuous ACR (ACRn) Score

Secondary: Continuous ACR (ACRn) Score

Clinical Trial Results:
A Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of CAM-3001 in participants with rheumatoid arthritis (RA).