Clinical Trial Results:
A Phase 2, randomized, doubleblind, placebocontrolled, multiple ascending dose study to evaluate the efficacy and safety of CAM3001 in participants with rheumatoid arthritis (RA).
Summary


EudraCT number 
200901473520 
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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
MICP219


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT01050998  
WHO universal trial number (UTN) 
  
Sponsors


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


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


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


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


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
27 Jul 2012


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
27 Jul 2012


Was the trial ended prematurely? 
No


General information about the trial


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 followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


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 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
247


From 65 to 84 years 
37


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


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


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  
Arms


Are arms mutually exclusive 
Yes


Arm title

Mavrilimumab 10 milligram (mg)  
Arm description 
Participants received Mavrilimumab (CAM3001) 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 
CAM3001


Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received Mavrilimumab (CAM3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks.


Arm title

Mavrilimumab 30 mg  
Arm description 
Participants received Mavrilimumab (CAM3001) 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 
CAM3001


Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received Mavrilimumab (CAM3001) 30 milligram (mg) injection subcutaneously every other week for 12 weeks.


Arm title

Mavrilimumab 50 mg  
Arm description 
Participants received Mavrilimumab (CAM3001) 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 
CAM3001


Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received Mavrilimumab (CAM3001) 50 mg injection subcutaneously every other week for 12 weeks.


Arm title

Mavrilimumab 100 mg  
Arm description 
Participants received Mavrilimumab (CAM3001) 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 
CAM3001


Other name 

Pharmaceutical forms 
Injection


Routes of administration 
Subcutaneous use


Dosage and administration details 
Participants received Mavrilimumab (CAM3001) 100 mg injection subcutaneously every other week for 12 weeks.


Arm title

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.





Baseline characteristics reporting groups


Reporting group title 
Mavrilimumab 10 milligram (mg)


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 30 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 50 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 100 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Placebo


Reporting group 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.  



End points reporting groups


Reporting group title 
Mavrilimumab 10 milligram (mg)


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 30 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 50 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Mavrilimumab 100 mg


Reporting group description 
Participants received Mavrilimumab (CAM3001) 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.  
Reporting group title 
Placebo


Reporting group 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.  
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 
Participants received Mavrilimumab (CAM3001) 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.


Subject analysis set title 
Mavrilimumab 100mg


Subject analysis set type 
Safety analysis  
Subject analysis set description 
Participants received Mavrilimumab (CAM3001) 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.



End point title 
Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using CReactive 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: 09.4, 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 intenttotreat (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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[1]}  
Pvalue 
= 0.578 ^{[2]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
4.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.5  
upper limit 
22  
Notes [1]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [2]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[3]}  
Pvalue 
< 0.001 ^{[4]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
30.7


Confidence interval 

level 
95%  
sides 
2sided


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]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[5]}  
Pvalue 
= 0.099 ^{[6]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
15.3


Confidence interval 

level 
95%  
sides 
2sided


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]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[7]}  
Pvalue 
< 0.001 ^{[8]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
35.5


Confidence interval 

level 
95%  
sides 
2sided


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]  pvalue was calculated using a twotailed Fisher’s exact test. 


End point title 
Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using CReactive 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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[9]}  
Pvalue 
= 0.543 ^{[10]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
6.4


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[11]}  
Pvalue 
= 0.011 ^{[12]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
26.3


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[13]}  
Pvalue 
= 0.108 ^{[14]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
16.6


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[15]}  
Pvalue 
= 0.001 ^{[16]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
32


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.5  
upper limit 
49  
Notes [15]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. [16]  European region: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[17]}  
Pvalue 
= 1 ^{[18]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[19]}  
Pvalue 
= 0.028 ^{[20]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
51.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.2  
upper limit 
77  
Notes [19]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. [20]  Japanese region: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[21]}  
Pvalue 
= 0.661 ^{[22]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
9.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[23]}  
Pvalue 
= 0.028 ^{[24]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
51.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.2  
upper limit 
77  
Notes [23]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. [24]  Japanese region: pvalue was calculated using a twotailed Fisher’s exact test. 


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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[25]}  
Pvalue 
= 0.152 ^{[26]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
13


Confidence interval 

level 
95%  
sides 
2sided


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]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[27]}  
Pvalue 
= 0.008 ^{[28]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
24.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7  
upper limit 
40.3  
Notes [27]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. [28]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[29]}  
Pvalue 
= 0.02 ^{[30]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
21.4


Confidence interval 

level 
95%  
sides 
2sided


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]  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[31]}  
Pvalue 
= 0.002 ^{[32]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
29


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
11.3  
upper limit 
45  
Notes [31]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. [32]  pvalue was calculated using a twotailed Fisher’s exact test. 


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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[33]}  
Pvalue 
= 0.328 ^{[34]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
9.9


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[35]}  
Pvalue 
= 0.084 ^{[36]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
17.2


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[37]}  
Pvalue 
= 0.049 ^{[38]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
20.2


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[39]}  
Pvalue 
= 0.03 ^{[40]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
22.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[41]}  
Pvalue 
= 0.188 ^{[42]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
26.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[43]}  
Pvalue 
= 0.01 ^{[44]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
57.4


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[45]}  
Pvalue 
= 0.188 ^{[46]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
26.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[47]}  
Pvalue 
= 0.01 ^{[48]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
57.4


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 


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. 



No statistical analyses for this end point 


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 
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. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.


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. 



No statistical analyses for this end point 


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 
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 [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. 



No statistical analyses for this end point 


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 
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. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.


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. 



No statistical analyses for this end point 


End point title 
Number of Participants With TreatmentEmergent Adverse Events (TEAEs) and TreatmentEmergent 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; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatmentemergent 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 (followup)


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. 



No statistical analyses for this end point 


End point title 
Number of Participants With Abnormal Vital Signs Reported as TreatmentEmergent 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 (followup)


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. 



No statistical analyses for this end point 


End point title 
Number of Participants With Abnormal Electrocardiogram (ECG) Results ^{[57]} ^{[58]}  
End point description 
12lead 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 (followup)


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


End point title 
Dyspnea Score at Day 85 ^{[71]} ^{[72]}  
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.


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


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. 



No statistical analyses for this end point 


End point title 
Number of Participants with Abnormal Clinical Laboratory Parameters Reported as TreatmentEmergent 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 anticyclic 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 (followup)


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. 



No statistical analyses for this end point 


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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[85]}  
Pvalue 
= 0.137  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[86]}  
Pvalue 
= 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.67


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[87]}  
Pvalue 
= 0.08  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.35


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[88]}  
Pvalue 
< 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.74


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[89]}  
Pvalue 
= 0.107  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.34


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[90]}  
Pvalue 
< 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.76


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[91]}  
Pvalue 
= 0.046  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.42


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[92]}  
Pvalue 
< 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


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. 


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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[93]}  
Pvalue 
= 0.086  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.4


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[94]}  
Pvalue 
= 0.016  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.55


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[95]}  
Pvalue 
= 0.059  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.43


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[96]}  
Pvalue 
= 0.002  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[97]}  
Pvalue 
= 0.107  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.39


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[98]}  
Pvalue 
= 0.007  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.64


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[99]}  
Pvalue 
= 0.084  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.41


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[100]}  
Pvalue 
= 0.002  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.73


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[101]}  
Pvalue 
= 0.785  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[102]}  
Pvalue 
= 0.014  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
1.19


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[103]}  
Pvalue 
= 0.931  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[104]}  
Pvalue 
= 0.07  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.86


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[105]}  
Pvalue 
= 0.854  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[106]}  
Pvalue 
= 0.011  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
1.25


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[107]}  
Pvalue 
= 0.271  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[108]}  
Pvalue 
= 0.031  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
1.03


Confidence interval 

level 
95%  
sides 
2sided


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. 


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: 09.4, 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




Statistical analysis title 
Statistical Analysis 1  
Statistical analysis description 
DAS28 (CRP): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[109]}  
Pvalue 
= 0.238  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
7


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis 2  
Statistical analysis description 
DAS28 (CRP): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[110]}  
Pvalue 
= 0.017  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
14.8


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis 3  
Statistical analysis description 
DAS28 (CRP): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[111]}  
Pvalue 
= 0.09  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
25.4  
Notes [111]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. 

Statistical analysis title 
Statistical Analysis 4  
Statistical analysis description 
DAS28 (CRP): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[112]}  
Pvalue 
= 0.015  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
15.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.9  
upper limit 
31  
Notes [112]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. 

Statistical analysis title 
Statistical Analysis 5  
Statistical analysis description 
DAS28 (ESR): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[113]}  
Pvalue 
= 0.412  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.2  
upper limit 
14  
Notes [113]  95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001. 

Statistical analysis title 
Statistical Analysis 6  
Statistical analysis description 
DAS28 (ESR): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[114]}  
Pvalue 
= 0.237  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
4.9


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis 7  
Statistical analysis description 
DAS28 (ESR): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[115]}  
Pvalue 
= 0.231  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
5.1


Confidence interval 

level 
95%  
sides 
2sided


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 title 
Statistical Analysis 8  
Statistical analysis description 
DAS28 (ESR): pvalue was calculated using a twotailed 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 
Prespecified


Analysis type 
other ^{[116]}  
Pvalue 
= 0.406  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
3.1


Confidence interval 

level 
95%  
sides 
2sided


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. 


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: 09.4, 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[117]}  
Pvalue 
= 0.182 ^{[118]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
8.7


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[119]}  
Pvalue 
= 0.11 ^{[120]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
10.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[121]}  
Pvalue 
= 0.104 ^{[122]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.3


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[123]}  
Pvalue 
= 0.016 ^{[124]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
16.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[125]}  
Pvalue 
= 0.115 ^{[126]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
6.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[127]}  
Pvalue 
= 0.052 ^{[128]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
8.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[129]}  
Pvalue 
= 0.115 ^{[130]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
6.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[131]}  
Pvalue 
= 0.115 ^{[132]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
6.4


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[133]}  
Pvalue 
= 1 ^{[134]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[135]}  
Pvalue 
= 0.059 ^{[136]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
38.2


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[137]}  
Pvalue 
= 0.591 ^{[138]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
10.5


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[139]}  
Pvalue 
= 0.57 ^{[140]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
13.2


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[141]}  
Pvalue 
= 0.529 ^{[142]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[143]}  
Pvalue 
= 1 ^{[144]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[145]}  
Pvalue 
= 1 ^{[146]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[147]}  
Pvalue 
= 1 ^{[148]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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]): pvalue was calculated using a twotailed Fisher’s exact test. 


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: 09.4, 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 (followup)




Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.604  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.145  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.282  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.047  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 


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:09.4, 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 (followup)




Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.237  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.005  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.134  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.265  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.013  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.952  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.246  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.004  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.126  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.125  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.005  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
= 0.831  
Method 
Logrank  
Confidence interval 

Statistical analysis title 
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 
Prespecified


Analysis type 
other  
Pvalue 
< 0.001  
Method 
Logrank  
Confidence interval 


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:09.4,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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[149]}  
Pvalue 
= 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[150]}  
Pvalue 
= 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[151]}  
Pvalue 
= 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[152]}  
Pvalue 
< 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[153]}  
Pvalue 
= 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[154]}  
Pvalue 
< 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[155]}  
Pvalue 
= 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 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[156]}  
Pvalue 
< 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 
2sided


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. 


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; selfassessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CReactive 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[157]}  
Pvalue 
= 0.589 ^{[158]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
4.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
12.1  
upper limit 
22  
Notes [157]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [158]  ACR50: pvalue was calculated using a twotailed Fisher’s exact test 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[159]}  
Pvalue 
= 0.032 ^{[160]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
20.2


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[161]}  
Pvalue 
= 1 ^{[162]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
16  
upper limit 
18  
Notes [161]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [162]  ACR50: pvalue was calculated using a twotailed Fisher’s exact test 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[163]}  
Pvalue 
< 0.001 ^{[164]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
33.3


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[165]}  
Pvalue 
= 0.212 ^{[166]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
8.9


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[167]}  
Pvalue 
= 0.011 ^{[168]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
18.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.8  
upper limit 
34  
Notes [167]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [168]  ACR50: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[169]}  
Pvalue 
= 0.446 ^{[170]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
4.7


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[171]}  
Pvalue 
= 0.003 ^{[172]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
22.1


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[173]}  
Pvalue 
= 1 ^{[174]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[175]}  
Pvalue 
= 0.317 ^{[176]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
4.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[177]}  
Pvalue 
= 1 ^{[178]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[179]}  
Pvalue 
= 0.106 ^{[180]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
9.5


Confidence interval 

level 
95%  
sides 
2sided


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: pvalue was calculated using a twotailed Fisher’s exact test. 


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; selfassessed 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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[181]}  
Pvalue 
= 1 ^{[182]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[183]}  
Pvalue 
= 0.12 ^{[184]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
16.1


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[185]}  
Pvalue 
= 1 ^{[186]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[187]}  
Pvalue 
= 0.005 ^{[188]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
29.2


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[189]}  
Pvalue 
= 0.382 ^{[190]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
20.9


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[191]}  
Pvalue 
= 0.087 ^{[192]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
39


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[193]}  
Pvalue 
= 1 ^{[194]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[195]}  
Pvalue 
= 0.028 ^{[196]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
51.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.2  
upper limit 
77  
Notes [195]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [196]  Japanese region: ACR20  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[197]}  
Pvalue 
= 0.175 ^{[198]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.1


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[199]}  
Pvalue 
= 0.271 ^{[200]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
8.5


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[201]}  
Pvalue 
= 0.026 ^{[202]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
17.3


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[203]}  
Pvalue 
= 0.021 ^{[204]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
18.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.4  
upper limit 
36  
Notes [203]  95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001. [204]  European region: ACR50  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[205]}  
Pvalue 
= 0.283 ^{[206]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
25.7


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[207]}  
Pvalue 
= 1 ^{[208]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[209]}  
Pvalue 
= 0.529 ^{[210]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[211]}  
Pvalue 
= 0.059 ^{[212]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
38.2


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[213]}  
Pvalue 
= 1 ^{[214]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[215]}  
Pvalue 
= 0.242 ^{[216]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
5.8


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[217]}  
Pvalue 
= 0.41 ^{[218]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
3.7


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[219]}  
Pvalue 
= 0.03 ^{[220]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
13.9


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[221]}  
Pvalue 
= 0.529 ^{[222]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[223]}  
Pvalue 
= 1 ^{[224]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[225]}  
Pvalue 
= 0.529 ^{[226]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 

Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[227]}  
Pvalue 
= 1 ^{[228]}  
Method 
Fisher exact  
Parameter type 
Percent difference  
Point estimate 
11.8


Confidence interval 

level 
95%  
sides 
2sided


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  pvalue was calculated using a twotailed Fisher’s exact test. 


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; selfassessed 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




No statistical analyses for this end point 


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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[229]}  
Pvalue 
= 0.051  
Method 
Repeated measures model  
Parameter type 
Adjusted Mean difference  
Point estimate 
14.05


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[230]}  
Pvalue 
= 0.003  
Method 
Repeated measures model  
Parameter type 
Adjusted Mean difference  
Point estimate 
21.23


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[231]}  
Pvalue 
= 0.322  
Method 
Repeated measures model  
Parameter type 
Adjusted Mean difference  
Point estimate 
7.09


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[232]}  
Pvalue 
< 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted Mean difference  
Point estimate 
32.03


Confidence interval 

level 
95%  
sides 
2sided


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. 


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




Statistical analysis title 
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 
Prespecified


Analysis type 
other ^{[233]}  
Pvalue 
= 0.071  
Method 
Repeated measures model  
Parameter type 
Adjusted Mean difference  
Point estimate 
14.49


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[234]}  
Pvalue 
= 0.013  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
19.43


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[235]}  
Pvalue 
= 0.32  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
7.84


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[236]}  
Pvalue 
< 0.001  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
31.37


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[237]}  
Pvalue 
= 0.483  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
12.11


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[238]}  
Pvalue 
= 0.075  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
31.24


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[239]}  
Pvalue 
= 0.815  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
4.22


Confidence interval 

level 
95%  
sides 
2sided


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 title 
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 
Prespecified


Analysis type 
other ^{[240]}  
Pvalue 
= 0.041  
Method 
Repeated measures model  
Parameter type 
Adjusted mean difference  
Point estimate 
36.11


Confidence interval 

level 
95%  
sides 
2sided


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. 