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Clinical Trial Results:
A Phase 2b Study to Evaluate the Efficacy and Safety of Mavrilimumab in Subjects with Moderate-to-Severe Rheumatoid Arthritis

Summary
EudraCT number	2011-005634-19
Trial protocol	HU EE CZ ES DE BG PL
Global end of trial date	29 Jan 2014

Results information
Results version number	v1(current)
This version publication date	10 Feb 2016
First version publication date	10 Feb 2016
Other versions

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

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Trial information

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Sponsor protocol code

CD-IA-CAM-3001-1071

ISRCTN number

US NCT number

NCT01706926

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

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

Public contact

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

Scientific contact

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

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

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

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

Analysis stage

Final

Date of interim/final analysis

29 Jan 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Jan 2014

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of 3 subcutaneous (SC) doses of mavrilimumab compared with placebo in combination with methotrexate (MTX) in participants with moderate-to-severe adult onset 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

27 Aug 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 31

Country: Number of subjects enrolled

Bulgaria: 9

Country: Number of subjects enrolled

Chile: 37

Country: Number of subjects enrolled

Colombia: 17

Country: Number of subjects enrolled

Czech Republic: 53

Country: Number of subjects enrolled

Estonia: 23

Country: Number of subjects enrolled

Germany: 9

Country: Number of subjects enrolled

Hungary: 7

Country: Number of subjects enrolled

Poland: 37

Country: Number of subjects enrolled

Russian Federation: 33

Country: Number of subjects enrolled

Serbia: 24

Country: Number of subjects enrolled

South Africa: 2

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Ukraine: 43

Worldwide total number of subjects

326

EEA total number of subjects

139

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

288

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 420 participants were screened out of which 326 participants were randomized and received investigational product in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo matched to mavrilimumab (CAM-3001) injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 milligram [mg] per week) through oral or parenteral route.

Arm type

Placebo

Investigational medicinal product name

Placebo matched to mavrilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mavrilimumab 30 mg

Arm description

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab 30 mg

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Mavrilimumab 100 mg

Arm description

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab 100 mg

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Mavrilimumab 150 mg

Arm description

Mavrilimumab (CAM-3001) 150 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Arm type

Experimental

Investigational medicinal product name

Mavrilimumab 150 mg

Investigational medicinal product code

CAM-3001

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Mavrilimumab (CAM-3001) 150 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Number of subjects in period 1	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Started	81	81	85	79
Completed	75	77	79	74
Not completed	6	4	6	5
Consent withdrawn by subject	2	-	1	2
Unspecified	4	4	4	3
Lost to follow-up	-	-	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

Mavrilimumab 30 mg

Reporting group description

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Reporting group title

Mavrilimumab 100 mg

Reporting group description

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Reporting group title

Mavrilimumab 150 mg

Reporting group description

Mavrilimumab (CAM-3001) 150 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Reporting group values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg	Total
Number of subjects	81	81	85	79	326
Age categorical
Units: Subjects
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	52.8 ± 10.6	51.2 ± 11.6	50.8 ± 11.9	52.6 ± 10.3	-
Gender, Male/Female
Units: participants
Female	75	70	70	67	282
Male	6	11	15	12	44

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

Mavrilimumab 30 mg

Reporting group description

Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Reporting group title

Mavrilimumab 100 mg

Reporting group description

Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Reporting group title

Mavrilimumab 150 mg

Reporting group description

Mavrilimumab (CAM-3001) 150 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

Primary: Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85

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End point title

Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85

End point description

DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, greater than or equal to (>=) 3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. The modified intent-to-treat (mITT) population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.

End point type

Primary

End point timeframe

Baseline and Day 85

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: units on a scale
arithmetic mean (standard error)
Baseline (n=81, 81, 85, 79)	5.78 ± 0.09	5.73 ± 0.104	5.91 ± 0.096	5.67 ± 0.086
Change at Day 85 (n=77, 76, 79, 78)	-0.68 ± 0.136	-1.37 ± 0.136	-1.64 ± 0.132	-1.9 ± 0.136

Statistical analysis 1

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. An estimate of the treatment difference and its 95 percent (%) confidence interval (CI) was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction. Differences <0 favored mavrilimumab.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.31

Variability estimate

Standard error of the mean

Dispersion value

0.193

Statistical analysis 2

Statistical analysis description

Analysis reported for change from baseline in DAS28 (CRP) at Day 85. An estimate of the treatment difference and its 95% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction. Differences <0 favored mavrilimumab.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

-0.58

Variability estimate

Standard error of the mean

Dispersion value

0.19

Statistical analysis 3

Statistical analysis description

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

-0.84

Variability estimate

Standard error of the mean

Dispersion value

0.193

Primary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

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End point title

Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

End point description

ACR20 was defined as >=20 percent (%) improvement, in: SJC and TJC and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Primary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	24.7	50.6	61.2	73.4

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

25.9

Confidence interval

level

95%

sides

2-sided

lower limit

11.5

upper limit

40.3

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

36.5

Confidence interval

level

95%

sides

2-sided

lower limit

22.5

upper limit

50.5

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

48.7

Confidence interval

level

95%

sides

2-sided

lower limit

35.2

upper limit

62.3

Secondary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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End point title

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

End point description

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and 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

Secondary

End point timeframe

Baseline up to Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)
TEAEs	46.9	50.6	42.4	54.4
TESAEs	1.2	4.9	5.9	2.5

No statistical analyses for this end point

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

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End point title

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

End point description

Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, absolute neutrophil count, leukocyte count, platelet count), serum chemistry (alanine transaminase, aspartate transaminase, bilirubin, gamma-glutamyl transferase), other serum chemistry (low-density lipoprotein cholesterol, triglycerides), and urinalysis. The safety population included all participants who received any dose of investigational product.

End point type

Secondary

End point timeframe

Baseline up to Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: participants
Anemia	1	1	0	0
Eosinophilia	0	0	1	0
Leukocytosis	2	0	0	0
Lymphopenia	0	0	0	1
Neutropenia	1	0	0	3
Alanine aminotransferase increased	0	1	1	1
Aspartate aminotransferase increased	0	1	1	0
Gamma-glutamyltransferase increased	0	1	0	0
Hypertransaminasaemia	0	0	2	2
Dislipidaemia	0	0	1	0
Hypercholesterolaemia	1	0	1	0
Hyperlipidaemia	0	2	0	3
Hyperkalaemia	0	0	0	1

No statistical analyses for this end point

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

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End point title

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

End point description

Vital sign assessments included blood pressure, pulse rate, temperature, weight 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

Secondary

End point timeframe

Baseline up to Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: participants
Hypertension	2	4	4	3
Weight increased	1	1	1	0
Pyrexia	0	1	0	0
Hot flush	0	0	1	0

No statistical analyses for this end point

Secondary: Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169

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End point title

Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169

End point description

Pulmonary function testing were performed by spirometry to assess forced expiratory volume in 1 second (FEV1), forced expiratory volume in 6 second (FEV6), and forced vital capacity (FVC). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV6 was the maximal volume of air exhaled in the 6 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 percentage of predicted values of these pulmonary function tests were calculated based on decreases from baseline and categorized as less than or equal to (=<) 15%, more than (>) 15 to =<20%, and >20%. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure for the specified threshold value mentioned parameter for each arm, respectively.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percent of pulmonary test values
number (not applicable)
FEV1 =<15% (n=42,67,75,75)	97.6	98.5	96	89.3
FEV1 >15 to 20% (n=42,67,75,75)	0	0	1.3	6.7
FEV1 >20% (n=42,67,75,75)	2.4	1.5	2.7	4
FEV6 =<15% (n=41,66,71,68)	97.6	97	94.4	89.7
FEV6 >15 to 20% (n=41,66,71,68)	0	1.5	1.4	1.5
FEV6 >20% (n=41,66,71,68)	2.4	1.5	4.2	8.8
FVC =<15% (n=42,67,75,75)	97.6	98.5	94.7	94.7
FVC >15 to 20% (n=42,67,75,75)	0	0	1.3	2.7
FVC >20% (n=42,67,75,75)	2.4	1.5	4	2.7

No statistical analyses for this end point

Secondary: Dyspnea Score at Day 169

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End point title

Dyspnea Score at Day 169

End point description

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

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	41	65	73	74
Units: units on a scale
arithmetic mean (standard deviation)	0.38 ± 0.62	0.22 ± 0.54	0.32 ± 0.73	0.28 ± 0.64

No statistical analyses for this end point

Secondary: Oxygen Saturation Level at Day 169

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End point title

Oxygen Saturation Level at Day 169

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

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	40	65	73	74
Units: percent saturation
arithmetic mean (standard deviation)	97.4 ± 1.4	97.4 ± 1.1	97.4 ± 1.1	97.3 ± 1.2

No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

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End point title

Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

End point description

ACR50 was defined as >=50% improvement, in: SJC and TJC and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	12.3	28.4	25.9	40.5

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.013

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.9

upper limit

28.2

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.03

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

13.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

25.3

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

28.2

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

41.1

Secondary: Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

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End point title

Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

End point description

ACR70 was defined as >=70% improvement, in: SJC and TJC and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	3.7	12.3	10.6	13.9

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.079

Method

Fisher exact

Parameter type

Percent difference

Point estimate

8.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

16.9

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.133

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

14.6

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.026

Method

Fisher exact

Parameter type

Percent difference

Point estimate

10.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

18.9

Secondary: American College of Rheumatology (ACRn) Score at Day 169

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End point title

American College of Rheumatology (ACRn) Score at Day 169

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 mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: units on a scale
arithmetic mean (standard error)	13.25 ± 4.63	29.04 ± 3.828	30.24 ± 3.623	40.72 ± 3.644

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.009

Method

Repeated measures model

Parameter type

Adjusted Mean difference

Point estimate

15.79

Confidence interval

level

95%

sides

2-sided

lower limit

3.96

upper limit

27.61

Variability estimate

Standard error of the mean

Dispersion value

6.007

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

16.99

Confidence interval

level

95%

sides

2-sided

lower limit

5.42

upper limit

28.56

Variability estimate

Standard error of the mean

Dispersion value

5.879

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

27.47

Confidence interval

level

95%

sides

2-sided

lower limit

15.87

upper limit

39.07

Variability estimate

Standard error of the mean

Dispersion value

5.892

Secondary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169

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 >1.2 with baseline DAS28 (CRP) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (CRP) >=3.2 to less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (CRP) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (CRP) >5.1. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)
No response	65.4	30.9	28.2	19
Moderate response	25.9	35.8	40	41.8
Good response	8.6	33.3	31.8	39.2

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Proportional odds analysis

Parameter type

Odds ratio (OR)

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.56

upper limit

8.8

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Proportional odds analysis

Parameter type

Odds ratio (OR)

Point estimate

4.81

Confidence interval

level

95%

sides

2-sided

lower limit

2.64

upper limit

8.92

Statistical analysis 3

Statistical analysis description

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Proportional odds analysis

Parameter type

Odds ratio (OR)

Point estimate

7.11

Confidence interval

level

95%

sides

2-sided

lower limit

3.85

upper limit

13.4

Secondary: Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169

Top of page

End point title

Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169

End point description

DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. Remission was defined as less than 2.6 DAS28 (CRP) score. Low disease activity was defined as less than 3.2 DAS28 (CRP) score. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)
DAS28 (CRP) Remission	4.9	21	17.6	19
Low Disease Activity	8.6	33.3	31.8	41.8

Statistical analysis 1

Statistical analysis description

DAS28 (CRP) remission: p-value estimated from fisher's exact test when number of placebo or active responders was less than 5.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

26.1

Statistical analysis 2

Statistical analysis description

DAS28 (CRP) remission: p-value estimated from fisher's exact test when number of placebo or active responders was less than 5.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.014

Method

Fisher exact

Parameter type

Percent difference

Point estimate

12.7

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

22.1

Statistical analysis 3

Statistical analysis description

DAS28 (CRP) remission: p-value estimated from fisher's exact test when number of placebo or active responders was less than 5.

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.007

Method

Fisher exact

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

23.9

Statistical analysis 4

Statistical analysis description

The analysis reported DAS28 (CRP) low disease activity response.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

24.7

Confidence interval

level

95%

sides

2-sided

lower limit

12.7

upper limit

36.6

Statistical analysis 5

Statistical analysis description

The analysis reported DAS28 (CRP) low disease activity response.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

23.1

Confidence interval

level

95%

sides

2-sided

lower limit

11.5

upper limit

34.8

Statistical analysis 6

Statistical analysis description

The analysis reported DAS28 (CRP) low disease activity response.

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Percent difference

Point estimate

33.1

Confidence interval

level

95%

sides

2-sided

lower limit

20.7

upper limit

45.6

Secondary: Mean Change From Baseline in Swollen and Tender Joint Count at Day 169

Top of page

End point title

Mean Change From Baseline in Swollen and Tender Joint Count at Day 169

End point description

Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1. Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: joint count
arithmetic mean (standard error)
SJC: Baseline (n=81,81,85,79)	14.44 ± 0.765	17.8 ± 1.126	16.82 ± 0.93	15.72 ± 0.795
SJC: Change at Day 169 (n=40,65,73,74)	-4.97 ± 0.932	-10.65 ± 0.809	-11.18 ± 0.771	-11.96 ± 0.787
TJC: Baseline (n=81,81,85,79)	26.26 ± 1.25	27.48 ± 1.553	26.96 ± 1.544	26.7 ± 1.284
TJC: Change at Day 169 (n=40,65,73,74)	-7.9 ± 1.447	-15.14 ± 1.265	-16.35 ± 1.207	-18.32 ± 1.234

Statistical analysis 1

Statistical analysis description

Analysis reported for change from baseline in swollen joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-5.68

Confidence interval

level

95%

sides

2-sided

lower limit

-8.12

upper limit

-3.24

Variability estimate

Standard error of the mean

Dispersion value

1.237

Statistical analysis 2

Statistical analysis description

Analysis reported for change from baseline in swollen joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-6.21

Confidence interval

level

95%

sides

2-sided

lower limit

-8.6

upper limit

-3.82

Variability estimate

Standard error of the mean

Dispersion value

1.211

Statistical analysis 3

Statistical analysis description

Analysis reported for change from baseline in swollen joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

-4.59

Variability estimate

Standard error of the mean

Dispersion value

1.219

Statistical analysis 4

Statistical analysis description

Analysis reported for change from baseline in tender joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-7.24

Confidence interval

level

95%

sides

2-sided

lower limit

-11.02

upper limit

-3.45

Variability estimate

Standard error of the mean

Dispersion value

1.922

Statistical analysis 5

Statistical analysis description

Analysis reported for change from baseline in tender joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-8.45

Confidence interval

level

95%

sides

2-sided

lower limit

-12.16

upper limit

-4.74

Variability estimate

Standard error of the mean

Dispersion value

1.884

Statistical analysis 6

Statistical analysis description

Analysis reported for change from baseline in tender joint count at Day 169.

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-10.42

Confidence interval

level

95%

sides

2-sided

lower limit

-14.17

upper limit

-6.67

Variability estimate

Standard error of the mean

Dispersion value

1.901

Secondary: Mean Change From Baseline in Patient Assessment of Pain at Day 169

Top of page

End point title

Mean Change From Baseline in Patient Assessment of Pain at Day 169

End point description

Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: mm
arithmetic mean (standard error)
Baseline (n=81, 81, 85, 79)	62.16 ± 2.093	62.65 ± 2.11	63.58 ± 2.034	62.35 ± 2.217
Change at Day 169 (n=40, 65, 73, 74)	-15.2 ± 3.006	-23.14 ± 2.563	-23.31 ± 2.446	-26.53 ± 2.483

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.045

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-7.94

Confidence interval

level

95%

sides

2-sided

lower limit

-15.72

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

3.95

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.004

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-11.32

Confidence interval

level

95%

sides

2-sided

lower limit

-19

upper limit

-3.65

Variability estimate

Standard error of the mean

Dispersion value

3.899

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.037

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-8.11

Confidence interval

level

95%

sides

2-sided

lower limit

-15.73

upper limit

-0.48

Variability estimate

Standard error of the mean

Dispersion value

3.876

Secondary: Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169

Top of page

End point title

Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169

End point description

Participants responded to a question, "Considering all the ways your arthritis affects you, how are you feeling today?" by using a 0 - 100 millimeter (mm) VAS, where 0 = very well and 100 = very poorly. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: mm
arithmetic mean (standard error)
Baseline (n=81, 81, 85, 79)	64.86 ± 1.892	63.79 ± 2.074	63.71 ± 1.957	62.39 ± 2.099
Change at Day 169 (n=40, 65, 73, 74)	-20.21 ± 3.148	-21.06 ± 2.685	-22.4 ± 2.56	-25.69 ± 2.6

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.837

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-8.99

upper limit

7.29

Variability estimate

Standard error of the mean

Dispersion value

4.137

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.589

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-2.19

Confidence interval

level

95%

sides

2-sided

lower limit

-10.18

upper limit

5.79

Variability estimate

Standard error of the mean

Dispersion value

4.058

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.18

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-5.48

Confidence interval

level

95%

sides

2-sided

lower limit

-13.52

upper limit

2.55

Variability estimate

Standard error of the mean

Dispersion value

4.083

Secondary: Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169

Top of page

End point title

Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169

End point description

Physician Global Assessment of Arthritis was measured by asking the physician to assess the participant's current arthritis disease activity by placing a vertical line on a 0 to 10 centimeter (cm) VAS, where 0 cm = very good and 10 cm = very bad. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: cm
arithmetic mean (standard error)
Baseline (n=81, 81, 85, 79)	6.6 ± 0.168	6.6 ± 0.162	6.81 ± 0.144	6.42 ± 0.166
Change at Day 169 (n=40, 65, 73, 74)	-2.39 ± 0.305	-3.81 ± 0.254	-3.85 ± 0.241	-3.95 ± 0.243

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.41

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

-0.63

Variability estimate

Standard error of the mean

Dispersion value

0.397

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.46

Confidence interval

level

95%

sides

2-sided

lower limit

-2.23

upper limit

-0.69

Variability estimate

Standard error of the mean

Dispersion value

0.389

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-1.56

Confidence interval

level

95%

sides

2-sided

lower limit

-2.33

upper limit

-0.79

Variability estimate

Standard error of the mean

Dispersion value

0.391

Secondary: Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169

Top of page

End point title

Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169

End point description

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range from 0 to 3; where 0 = least difficulty and 3 = extreme difficulty. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: units on a scale
arithmetic mean (standard error)
Baseline (n=81, 80, 85, 79)	1.63 ± 0.054	1.52 ± 0.07	1.58 ± 0.056	1.58 ± 0.059
Change at Day 169 (n=40, 65, 73, 74)	-0.29 ± 0.081	-0.37 ± 0.072	-0.46 ± 0.068	-0.55 ± 0.069

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.479

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.108

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.124

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.16

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.106

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.017

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.107

Secondary: Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169

Top of page

End point title

Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169

End point description

CRP is a substance produced by the liver that increases in the presence of inflammation in the body. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in underlying disease. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "N" (Number of participants analyzed) signifies those participants who were evaluable for this measure.

End point type

Secondary

End point timeframe

Baseline, Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	38	63	72	74
Units: ratio
geometric mean (geometric coefficient of variation)	1.2971 ± 83.3	0.8784 ± 102.8	0.5197 ± 287.4	0.5856 ± 153.3

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.017

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.92

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

112

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

0.63

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.66

Secondary: Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169

Top of page

End point title

Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169

End point description

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. The farther the red blood cells have descended, the greater the inflammatory response. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "N" (Number of participants analyzed) signifies those participants who were evaluable for this measure.

End point type

Secondary

End point timeframe

Baseline, Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	40	64	73	74
Units: ratio
geometric mean (geometric coefficient of variation)	0.89 ± 57	0.67 ± 56.4	0.62 ± 55.3	0.58 ± 61

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.003

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.89

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

113

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.84

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

114

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Repeated measures model

Parameter type

Adjusted geometric mean ratio

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.75

Secondary: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169

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End point title

Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169

End point description

The SDAI was the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 - 10 cm VAS; and C-reactive protein (CRP) (milligram per deciliter [mg/dL]). The SDAI total score ranges from 0 to 86, where higher scores indicates greater affection due to disease activity. SDAI remission was defined as a score less than or equal to 3.3. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	1.2	6.2	2.4	5.1

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.21

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

10.7

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 1

Method

Fisher exact

Parameter type

Percent difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

5.1

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.207

Method

Fisher exact

Parameter type

Percent difference

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

9.2

Secondary: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169

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End point title

Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169

End point description

The CDAI was the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 - 10 cm VAS. The CDAI total score ranges from 0 to 76 where higher scores indicates greater affection due to disease activity. CDAI remission was defined as a score less than or equal to 2.8. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	1.2	6.2	3.5	7.6

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.21

Method

Fisher exact

Parameter type

Percent difference

Point estimate

4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

10.7

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.621

Method

Fisher exact

Parameter type

Percent difference

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

6.9

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.062

Method

Fisher exact

Parameter type

Percent difference

Point estimate

6.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

12.7

Secondary: Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169

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End point title

Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169

End point description

ACR/EULAR remission was defined as swollen joint count (0-66), tender joint count (0-68), CRP (mg/dL) and participant global assessment (0-10) all less than or equal to one. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.

End point type

Secondary

End point timeframe

Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	0	3.7	1.2	1.3

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.245

Method

Fisher exact

Parameter type

Percent difference

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

7.8

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 1

Method

Fisher exact

Parameter type

Percent difference

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

3.5

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.494

Method

Fisher exact

Parameter type

Percent difference

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

3.7

Secondary: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169

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End point title

Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169

End point description

FACIT-F is a 13-item questionnaire questionnaire to measure the degree of fatigue experiences by participants in the previous 7 days. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant’s response to the questions (with the exception of 2 negatively stated), greater was the participant’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score) where higher sore represent less fatigue. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. 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 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: units on a scale
arithmetic mean (standard error)
Baseline (n=79, 80, 84, 79)	26.75 ± 0.824	28.91 ± 1.078	28.45 ± 0.998	27.82 ± 0.95
Change at Day 169 (n=40, 65, 73, 74)	4.53 ± 1.225	5.72 ± 1.039	6.8 ± 0.988	8.45 ± 0.997

Statistical analysis 1

Comparison groups

Placebo v Mavrilimumab 30 mg

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.463

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.99

upper limit

4.35

Variability estimate

Standard error of the mean

Dispersion value

1.608

Statistical analysis 2

Comparison groups

Placebo v Mavrilimumab 100 mg

Number of subjects included in analysis

166

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.151

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

2.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

5.37

Variability estimate

Standard error of the mean

Dispersion value

1.574

Statistical analysis 3

Comparison groups

Placebo v Mavrilimumab 150 mg

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.014

Method

Repeated measures model

Parameter type

Adjusted mean difference

Point estimate

3.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

7.02

Variability estimate

Standard error of the mean

Dispersion value

1.578

Secondary: Serum Concentrations of Mavrilimumab

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End point title

Serum Concentrations of Mavrilimumab ^[1]

End point description

Serum concentrations after multiple subcutaneous doses of mavrilimumab were calculated for each cohort (30mg, 100mg and 150mg). In the below table, '99999' indicates data was not reported for the geometric coefficient of variation for the respective timepoint. The pharmacokinetic (PK) population included all participants who received mavrilimumab and for whom serum concentrations of mavrilimumab were available for PK data analyses. Here "n" signifies participants who were evaluable for the specified time point for each arm, respectively.

End point type

Secondary

End point timeframe

Baseline, Day 8, 15, 29, 85, 141, and 169

Notes
[1] - 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: Placebo-treated subjects (N=81) were excluded from the pharmacokinetic analysis.

End point values	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	85	79
Units: nanogram per milliliter
geometric mean (geometric coefficient of variation)
Baseline (n=80, 85, 79)	0 ± 894.4	0 ± 99999	0 ± 862
Day 8 (n=78, 83, 78)	617.49 ± 111.8	3563.31 ± 49.3	6087.06 ± 43.4
Day 15 (n=78, 84, 78)	154.6 ± 194.2	2479.96 ± 52.1	4616.35 ± 42.6
Day 29 (n=77, 85, 76)	217.67 ± 248.3	4503.97 ± 54.8	7843.66 ± 42.9
Day 85 (n=74, 81, 77)	201.57 ± 162.8	6538.22 ± 52.7	13213.93 ± 50.1
Day 141 (n=67, 75, 71)	258.77 ± 136.9	2932.8 ± 75.6	9241.31 ± 52.1
Day 169 (n=63, 73, 74)	348.97 ± 141.2	5282.37 ± 62	9178.47 ± 56.6

No statistical analyses for this end point

Secondary: Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at any Visit

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End point title

Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at any Visit

End point description

Immunogenicity assessment included determination of anti-drug (mavrilimumab) antibodies in serum samples. ADA detection measured by using electrochemiluminescence assays. The immunogenicity population included all participants who received at least 1 dose of mavrilimumab and for whom at least one serum sample for immunogenicity testing was available.

End point type

Secondary

End point timeframe

Day 1 to Day 169

End point values	Placebo	Mavrilimumab 30 mg	Mavrilimumab 100 mg	Mavrilimumab 150 mg
Number of subjects analysed	81	81	85	79
Units: percentage of participants
number (not applicable)	2.5	16	3.5	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to Day 169

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

PLACEBO

Reporting group description

Reporting group title

MAVRILIMUMAB 100MG

Reporting group description

Reporting group title

MAVRILIMUMAB 150MG

Reporting group description

Reporting group title

MAVRILIMUMAB 30MG

Reporting group description

Serious adverse events	PLACEBO	MAVRILIMUMAB 100MG	MAVRILIMUMAB 150MG	MAVRILIMUMAB 30MG
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 81 (1.23%)	5 / 85 (5.88%)	2 / 79 (2.53%)	4 / 81 (4.94%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of the cervix
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Lower limb fracture
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial tachycardia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dyspepsia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cystocele
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	PLACEBO	MAVRILIMUMAB 100MG	MAVRILIMUMAB 150MG	MAVRILIMUMAB 30MG
Total subjects affected by non serious adverse events
subjects affected / exposed	38 / 81 (46.91%)	33 / 85 (38.82%)	42 / 79 (53.16%)	38 / 81 (46.91%)
Vascular disorders
Haematoma
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Hot flush
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Hypertension
subjects affected / exposed	2 / 81 (2.47%)	4 / 85 (4.71%)	3 / 79 (3.80%)	4 / 81 (4.94%)
occurrences all number	2	5	3	4
Venous insufficiency
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Feeling hot
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Influenza like illness
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	0	0	1	1
Injection site erythema
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	3	0
Injection site haematoma
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Injection site swelling
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	1	0	2	2
Injection site reaction
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Oedema peripheral
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Pyrexia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Immune system disorders
Allergy to arthropod bite
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Drug hypersensitivity
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	2 / 79 (2.53%)	1 / 81 (1.23%)
occurrences all number	1	0	2	1
Hypersensitivity
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Endometriosis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Uterine polyp
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Vaginal discharge
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Bronchospasm
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Cough
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Obstructive airways disorder
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Pleural effusion
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Pulmonary mass
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Rhinorrhoea
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Depression
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	2 / 81 (2.47%)
occurrences all number	0	0	1	2
Dyssomnia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Insomnia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	0	1	1	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	1
Blood pressure increased
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Weight increased
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	1	0	1
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Animal bite
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Bone contusion
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Chemical poisoning
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Clavicle fracture
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Contusion
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0
Epicondylitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Fall
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Injection related reaction
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Laceration
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Limb injury
subjects affected / exposed	0 / 81 (0.00%)	2 / 85 (2.35%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	2	0	0
Muscle contusion
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0
Cardiac disorders
Arrhythmia supraventricular
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Cardiac failure
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Cardiovascular insufficiency
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	2 / 81 (2.47%)	4 / 85 (4.71%)	6 / 79 (7.59%)	5 / 81 (6.17%)
occurrences all number	2	4	8	5
Intercostal neuralgia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Sciatica
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	0	0	1
Eosinophilia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Leukocytosis
subjects affected / exposed	2 / 81 (2.47%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0
Lymphopenia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Neutropenia
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	3 / 79 (3.80%)	0 / 81 (0.00%)
occurrences all number	1	0	4	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	1
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 81 (0.00%)	2 / 85 (2.35%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	2	0	0
Keratitis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	1	0	1	0
Abdominal pain upper
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Cheilitis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Constipation
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Dental caries
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0
Diarrhoea
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	2 / 79 (2.53%)	1 / 81 (1.23%)
occurrences all number	0	0	2	1
Dyspepsia
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0
Gastritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	2 / 79 (2.53%)	0 / 81 (0.00%)
occurrences all number	0	0	2	0
Gingival swelling
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Haemorrhoids
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Mouth cyst
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Nausea
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	1	0	1	0
Vomiting
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	0 / 81 (0.00%)	2 / 85 (2.35%)	2 / 79 (2.53%)	0 / 81 (0.00%)
occurrences all number	0	2	2	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Dermatitis contact
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Erythema
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Hyperhidrosis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Intertrigo
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Pruritus
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	2 / 79 (2.53%)	0 / 81 (0.00%)
occurrences all number	0	0	2	0
Rash
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0
Urticaria
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Renal colic
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Joint swelling
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Osteoarthritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Rheumatoid arthritis
subjects affected / exposed	4 / 81 (4.94%)	2 / 85 (2.35%)	0 / 79 (0.00%)	2 / 81 (2.47%)
occurrences all number	6	2	0	3
Rheumatoid nodule
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	1
Sjogren's syndrome
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Spinal osteoarthritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Spinal pain
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Tendonitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Infections and infestations
Body tinea
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Cellulitis
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	1	0	1	0
Bronchitis
subjects affected / exposed	6 / 81 (7.41%)	1 / 85 (1.18%)	4 / 79 (5.06%)	3 / 81 (3.70%)
occurrences all number	6	1	4	3
Cystitis
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	1
Ear infection
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Fungal skin infection
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	0	0	1	1
Gastroenteritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	2 / 79 (2.53%)	1 / 81 (1.23%)
occurrences all number	0	0	2	1
Gastrointestinal viral infection
subjects affected / exposed	2 / 81 (2.47%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	2	0	1	0
Gingivitis
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Herpes simplex
subjects affected / exposed	2 / 81 (2.47%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0
Influenza
subjects affected / exposed	0 / 81 (0.00%)	3 / 85 (3.53%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	0	3	1	1
Lyme disease
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Nasopharyngitis
subjects affected / exposed	6 / 81 (7.41%)	3 / 85 (3.53%)	6 / 79 (7.59%)	4 / 81 (4.94%)
occurrences all number	6	4	6	5
Omphalitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Periodontitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	0 / 79 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	1 / 81 (1.23%)
occurrences all number	0	0	1	1
Pneumonia
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0
Rhinitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	2 / 79 (2.53%)	2 / 81 (2.47%)
occurrences all number	0	0	2	2
Sinusitis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Skin infection
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Tinea pedis
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Tinea versicolour
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Tonsillitis
subjects affected / exposed	1 / 81 (1.23%)	0 / 85 (0.00%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	1 / 79 (1.27%)	2 / 81 (2.47%)
occurrences all number	1	1	1	2
Viral upper respiratory tract infection
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	1 / 79 (1.27%)	2 / 81 (2.47%)
occurrences all number	0	1	1	2
Urinary tract infection
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	1 / 79 (1.27%)	2 / 81 (2.47%)
occurrences all number	1	1	1	2
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	0 / 81 (0.00%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0
Hypercholesterolaemia
subjects affected / exposed	1 / 81 (1.23%)	1 / 85 (1.18%)	0 / 79 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0
Hyperkalaemia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	1 / 79 (1.27%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0
Hyperlipidaemia
subjects affected / exposed	0 / 81 (0.00%)	0 / 85 (0.00%)	3 / 79 (3.80%)	2 / 81 (2.47%)
occurrences all number	0	0	3	2

More information

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Were there any global substantial amendments to the protocol? Yes

10 Dec 2010

The anticipated number of study centers was increased from 90 to 100. The maximum duration of the study was corrected from 40 weeks to 44 weeks. Reference to the data safety monitoring board (DSMB) was removed from the Study-stopping Criteria section of the protocol. A section describing un-blinding in the event of a suspected unexpected serious adverse reaction (SUSAR) was added to the protocol. Language in the protocol was clarified to state that investigational product was not to be removed from the storage area until all protocol-specific assessments were completed and the subject was ready for dosing. Instructions relating to the preparation of placebo were added to the protocol. In the case of a clinically significant pulmonary abnormality, the language in the protocol was clarified to make it clear that the investigator was the responsible person, in collaboration with the sponsor, to make the decision to resume administration of investigational product. Changes in eligibility criteria. A diffusing capacity for carbon monoxide (DLCO) assessment was added to the protocol. The need for a sample collection for anti-drug antibodies (ADA) analysis in the event of a severe hypersensitivity reaction was removed from the protocol.

Were there any global interruptions to the trial? No

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

Non-compartmental analyses was not performed for pharmacokinetics parameters due to limited sampling schedule

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Clinical trials

Clinical Trial Results: A Phase 2b Study to Evaluate the Efficacy and Safety of Mavrilimumab in Subjects with Moderate-to-Severe Rheumatoid Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85

Primary: Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85

Primary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

Primary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

Secondary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Secondary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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

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

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

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

Secondary: Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169

Secondary: Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169

Secondary: Dyspnea Score at Day 169

Secondary: Dyspnea Score at Day 169

Secondary: Oxygen Saturation Level at Day 169

Secondary: Oxygen Saturation Level at Day 169

Secondary: Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

Secondary: Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

Secondary: Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

Secondary: Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

Secondary: American College of Rheumatology (ACRn) Score at Day 169

Secondary: American College of Rheumatology (ACRn) Score at Day 169

Secondary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169

Secondary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169

Secondary: Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169

Secondary: Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169

Secondary: Mean Change From Baseline in Swollen and Tender Joint Count at Day 169

Secondary: Mean Change From Baseline in Swollen and Tender Joint Count at Day 169

Secondary: Mean Change From Baseline in Patient Assessment of Pain at Day 169

Secondary: Mean Change From Baseline in Patient Assessment of Pain at Day 169

Secondary: Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169

Secondary: Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169

Secondary: Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169

Secondary: Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169

Secondary: Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169

Secondary: Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169

Secondary: Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169

Secondary: Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169

Secondary: Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169

Secondary: Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169

Secondary: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169

Secondary: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169

Secondary: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169

Secondary: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169

Secondary: Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169

Secondary: Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169

Secondary: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169

Secondary: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169

Secondary: Serum Concentrations of Mavrilimumab

Secondary: Serum Concentrations of Mavrilimumab

Secondary: Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at any Visit

Secondary: Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at any Visit

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2b Study to Evaluate the Efficacy and Safety of Mavrilimumab in Subjects with Moderate-to-Severe Rheumatoid Arthritis