Trial Outcomes & Findings for A Study of Mavrilimumab in Subjects With Moderate-to-Severe Rheumatoid Arthritis (NCT NCT01706926)

Last Updated: 2016-09-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

420 participants

Primary outcome timeframe

Baseline and Day 85

Results posted on

2016-09-27

Participant Flow

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

Participant milestones

Participant milestones
Measure	Placebo 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.	Mavrilimumab 30 mg 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 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 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.
Overall Study STARTED	81	81	85	79
Overall Study COMPLETED	75	77	79	74
Overall Study NOT COMPLETED	6	4	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	Mavrilimumab 30 mg 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 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 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.
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Withdrawal by Subject	2	0	1	2
Overall Study Other	4	4	4	3

Baseline Characteristics

A Study of Mavrilimumab in Subjects With Moderate-to-Severe Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.	Total n=326 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 10.6 • n=5 Participants	51.2 years STANDARD_DEVIATION 11.6 • n=7 Participants	50.8 years STANDARD_DEVIATION 11.9 • n=5 Participants	52.6 years STANDARD_DEVIATION 10.3 • n=4 Participants	51.8 years STANDARD_DEVIATION 11.1 • n=21 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	70 Participants n=7 Participants	70 Participants n=5 Participants	67 Participants n=4 Participants	282 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants	12 Participants n=4 Participants	44 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Day 85

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85 Baseline (n=81, 81, 85, 79)	5.78 units on a scale Standard Error 0.090	5.73 units on a scale Standard Error 0.104	5.91 units on a scale Standard Error 0.096	5.67 units on a scale Standard Error 0.086
Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 85 Change at Day 85 (n=77, 76, 79, 78)	-0.68 units on a scale Standard Error 0.136	-1.37 units on a scale Standard Error 0.136	-1.64 units on a scale Standard Error 0.132	-1.90 units on a scale Standard Error 0.136

PRIMARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169	24.7 percentage of participants	50.6 percentage of participants	61.2 percentage of participants	73.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 169

Population: The safety population included all participants who received any dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	46.9 percentage of participants	50.6 percentage of participants	42.4 percentage of participants	54.4 percentage of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	1.2 percentage of participants	4.9 percentage of participants	5.9 percentage of participants	2.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 169

Population: The safety population included all participants who received any dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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 Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Anemia	1 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Eosinophilia	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Leukocytosis	2 participants	0 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Lymphopenia	0 participants	0 participants	0 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Neutropenia	1 participants	0 participants	0 participants	3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Alanine aminotransferase increased	0 participants	1 participants	1 participants	1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Aspartate aminotransferase increased	0 participants	1 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Gamma-glutamyltransferase increased	0 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertransaminasaemia	0 participants	0 participants	2 participants	2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Dislipidaemia	0 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hypercholesterolaemia	1 participants	0 participants	1 participants	0 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hyperlipidaemia	0 participants	2 participants	0 participants	3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) Hyperkalaemia	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline up to Day 169

Population: The safety population included all participants who received any dose of investigational product.

Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiration rate. Vital signs abnormalities reported as TEAEs were reported.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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 Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Pyrexia	0 participants	1 participants	0 participants	0 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Hypertension	2 participants	4 participants	4 participants	3 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Weight increased	1 participants	1 participants	1 participants	0 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) Hot flush	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 169

Population: 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.

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 six 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 percent (%), more than (\>) 15 to =\<20%, and \>20%.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV1 =<15% (n=42,67,75,75)	97.6 percent of pulmonary test values	98.5 percent of pulmonary test values	96.0 percent of pulmonary test values	89.3 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV1 >15 to 20% (n=42,67,75,75)	0.0 percent of pulmonary test values	0.0 percent of pulmonary test values	1.3 percent of pulmonary test values	6.7 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV1 >20% (n=42,67,75,75)	2.4 percent of pulmonary test values	1.5 percent of pulmonary test values	2.7 percent of pulmonary test values	4.0 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV6 =<15% (n=41,66,71,68)	97.6 percent of pulmonary test values	97.0 percent of pulmonary test values	94.4 percent of pulmonary test values	89.7 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV6 >15 to 20% (n=41,66,71,68)	0.0 percent of pulmonary test values	1.5 percent of pulmonary test values	1.4 percent of pulmonary test values	1.5 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FEV6 >20% (n=41,66,71,68)	2.4 percent of pulmonary test values	1.5 percent of pulmonary test values	4.2 percent of pulmonary test values	8.8 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FVC =<15% (n=42,67,75,75)	97.6 percent of pulmonary test values	98.5 percent of pulmonary test values	94.7 percent of pulmonary test values	94.7 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FVC >15 to 20% (n=42,67,75,75)	0.0 percent of pulmonary test values	0.0 percent of pulmonary test values	1.3 percent of pulmonary test values	2.7 percent of pulmonary test values
Percentage of Pulmonary Function Test Values Below Threshold Values at Day 169 FVC >20% (n=42,67,75,75)	2.4 percent of pulmonary test values	1.5 percent of pulmonary test values	4.0 percent of pulmonary test values	2.7 percent of pulmonary test values

SECONDARY outcome

Timeframe: Day 169

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants 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.	Mavrilimumab 30 mg n=65 Participants 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 n=73 Participants 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 n=74 Participants 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.
Dyspnea Score at Day 169	0.38 units on a scale Standard Deviation 0.62	0.22 units on a scale Standard Deviation 0.54	0.32 units on a scale Standard Deviation 0.73	0.28 units on a scale Standard Deviation 0.64

SECONDARY outcome

Timeframe: Day 169

Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants 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.	Mavrilimumab 30 mg n=65 Participants 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 n=73 Participants 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 n=74 Participants 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.
Oxygen Saturation Level at Day 169	97.4 percent saturation Standard Deviation 1.4	97.4 percent saturation Standard Deviation 1.1	97.4 percent saturation Standard Deviation 1.1	97.3 percent saturation Standard Deviation 1.2

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169	12.3 percentage of participants	28.4 percentage of participants	25.9 percentage of participants	40.5 percentage of participants

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169	3.7 percentage of participants	12.3 percentage of participants	10.6 percentage of participants	13.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 169

Population: 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 participants who were evaluable for this measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants 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.	Mavrilimumab 30 mg n=63 Participants 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 n=72 Participants 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 n=74 Participants 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.
Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169	13.25 units on a scale Standard Error 4.630	29.04 units on a scale Standard Error 3.828	30.24 units on a scale Standard Error 3.623	40.72 units on a scale Standard Error 3.644

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169 No response	65.4 percentage of participants 0.090	30.9 percentage of participants 0.104	28.2 percentage of participants 0.096	19.0 percentage of participants 0.086
Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169 Moderate response	25.9 percentage of participants 0.136	35.8 percentage of participants 0.136	40.0 percentage of participants 0.132	41.8 percentage of participants 0.136
Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169 Good response	8.6 percentage of participants	33.3 percentage of participants	31.8 percentage of participants	39.2 percentage of participants

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169 DAS28 (CRP) Remission	4.9 percentage of participants	21.0 percentage of participants	17.6 percentage of participants	19.0 percentage of participants
Percentage of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169 Low Disease Activity	8.6 percentage of participants	33.3 percentage of participants	31.8 percentage of participants	41.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 169

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Swollen and Tender Joint Count at Day 169 SJC: Baseline (n=81,81,85,79)	14.44 joint count Standard Error 0.765	17.80 joint count Standard Error 1.126	16.82 joint count Standard Error 0.930	15.72 joint count Standard Error 0.795
Mean Change From Baseline in Swollen and Tender Joint Count at Day 169 SJC: Change at Day 169 (n=40,65,73,74)	-4.97 joint count Standard Error 0.932	-10.65 joint count Standard Error 0.809	-11.18 joint count Standard Error 0.771	-11.96 joint count Standard Error 0.787
Mean Change From Baseline in Swollen and Tender Joint Count at Day 169 TJC: Baseline (n=81,81,85,79)	26.26 joint count Standard Error 1.250	27.48 joint count Standard Error 1.553	26.96 joint count Standard Error 1.544	26.70 joint count Standard Error 1.284
Mean Change From Baseline in Swollen and Tender Joint Count at Day 169 TJC: Change at Day 169 (n=40,65,73,74)	-7.90 joint count Standard Error 1.447	-15.14 joint count Standard Error 1.265	-16.35 joint count Standard Error 1.207	-18.32 joint count Standard Error 1.234

SECONDARY outcome

Timeframe: Baseline and Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Patient Assessment of Pain at Day 169 Baseline (n=81, 81, 85, 79)	62.16 mm Standard Error 2.093	62.65 mm Standard Error 2.110	63.58 mm Standard Error 2.034	62.35 mm Standard Error 2.217
Mean Change From Baseline in Patient Assessment of Pain at Day 169 Change at Day 169 (n=40, 65, 73, 74)	-15.20 mm Standard Error 3.006	-23.14 mm Standard Error 2.563	-23.31 mm Standard Error 2.446	-26.53 mm Standard Error 2.483

SECONDARY outcome

Timeframe: Baseline and Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169 Baseline (n=81, 81, 85, 79)	64.86 mm Standard Error 1.892	63.79 mm Standard Error 2.074	63.71 mm Standard Error 1.957	62.39 mm Standard Error 2.099
Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169 Change at Day 169 (n=40, 65, 73, 74)	-20.21 mm Standard Error 3.148	-21.06 mm Standard Error 2.685	-22.40 mm Standard Error 2.560	-25.69 mm Standard Error 2.600

SECONDARY outcome

Timeframe: Baseline and Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169 Baseline (n=81, 81, 85, 79)	6.60 cm Standard Error 0.168	6.60 cm Standard Error 0.162	6.81 cm Standard Error 0.144	6.42 cm Standard Error 0.166
Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169 Change at Day 169 (n=40, 65, 73, 74)	-2.39 cm Standard Error 0.305	-3.81 cm Standard Error 0.254	-3.85 cm Standard Error 0.241	-3.95 cm Standard Error 0.243

SECONDARY outcome

Timeframe: Baseline and Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169 Baseline (n=81, 80, 85, 79)	1.63 units on a scale Standard Error 0.054	1.52 units on a scale Standard Error 0.070	1.58 units on a scale Standard Error 0.056	1.58 units on a scale Standard Error 0.059
Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169 Change at Day 169 (n=40, 65, 73, 74)	-0.29 units on a scale Standard Error 0.081	-0.37 units on a scale Standard Error 0.072	-0.46 units on a scale Standard Error 0.068	-0.55 units on a scale Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline, Day 169

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants 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.	Mavrilimumab 30 mg n=63 Participants 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 n=72 Participants 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 n=74 Participants 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.
Ratio of Change From Baseline in C-Reactive Protein (CRP) at Day 169	1.2971 ratio Geometric Coefficient of Variation 83.3	0.8784 ratio Geometric Coefficient of Variation 102.8	0.5197 ratio Geometric Coefficient of Variation 287.4	0.5856 ratio Geometric Coefficient of Variation 153.3

SECONDARY outcome

Timeframe: Baseline, Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants 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.	Mavrilimumab 30 mg n=64 Participants 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 n=73 Participants 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 n=74 Participants 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.
Ratio of Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Day 169	0.89 ratio Geometric Coefficient of Variation 57.0	0.67 ratio Geometric Coefficient of Variation 56.4	0.62 ratio Geometric Coefficient of Variation 55.3	0.58 ratio Geometric Coefficient of Variation 61.0

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Day 169	1.2 percentage of participants 0.054	6.2 percentage of participants 0.070	2.4 percentage of participants 0.056	5.1 percentage of participants 0.059

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169	1.2 percentage of participants 0.054	6.2 percentage of participants 0.070	3.5 percentage of participants 0.056	7.6 percentage of participants 0.059

SECONDARY outcome

Timeframe: Day 169

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169	0.0 percentage of participants 0.054	3.7 percentage of participants 0.070	1.2 percentage of participants 0.056	1.3 percentage of participants 0.059

SECONDARY outcome

Timeframe: Baseline and Day 169

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169 Baseline (n=79, 80, 84, 79)	26.75 units on a scale Standard Error 0.824	28.91 units on a scale Standard Error 1.078	28.45 units on a scale Standard Error 0.998	27.82 units on a scale Standard Error 0.950
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-fatigue) at Day 169 Change at Day 169 (n=40, 65, 73, 74)	4.53 units on a scale Standard Error 1.225	5.72 units on a scale Standard Error 1.039	6.80 units on a scale Standard Error 0.988	8.45 units on a scale Standard Error 0.997

SECONDARY outcome

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

Population: 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.

Serum concentrations after multiple subcutaneous doses of mavrilimumab were calculated for each cohort (30mg, 100mg and 150mg). Geometric coefficient of variation at Baseline for cohorts 30mg and 150mg were calculated as the negligible mean value was observed.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=85 Participants 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 n=79 Participants 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 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.
Serum Concentrations of Mavrilimumab Baseline (n=80, 85, 79)	0.00 nanogram per milliliter Geometric Coefficient of Variation 894.4	0.00 nanogram per milliliter Geometric Coefficient of Variation NA Geometric coefficient of variation could not be calculated as mean and geometric mean were zero at this time point.	0.00 nanogram per milliliter Geometric Coefficient of Variation 862.0	—
Serum Concentrations of Mavrilimumab Day 8 (n=78, 83, 78)	617.49 nanogram per milliliter Geometric Coefficient of Variation 111.8	3563.31 nanogram per milliliter Geometric Coefficient of Variation 49.3	6087.06 nanogram per milliliter Geometric Coefficient of Variation 43.4	—
Serum Concentrations of Mavrilimumab Day 15 (n=78, 84, 78)	154.60 nanogram per milliliter Geometric Coefficient of Variation 194.2	2479.96 nanogram per milliliter Geometric Coefficient of Variation 52.1	4616.35 nanogram per milliliter Geometric Coefficient of Variation 42.6	—
Serum Concentrations of Mavrilimumab Day 29 (n=77, 85, 76)	217.67 nanogram per milliliter Geometric Coefficient of Variation 248.3	4503.97 nanogram per milliliter Geometric Coefficient of Variation 54.8	7843.66 nanogram per milliliter Geometric Coefficient of Variation 42.9	—
Serum Concentrations of Mavrilimumab Day 85 (n=74, 81, 77)	201.57 nanogram per milliliter Geometric Coefficient of Variation 162.8	6538.22 nanogram per milliliter Geometric Coefficient of Variation 52.7	13213.93 nanogram per milliliter Geometric Coefficient of Variation 50.1	—
Serum Concentrations of Mavrilimumab Day 141 (n=67, 75, 71)	258.77 nanogram per milliliter Geometric Coefficient of Variation 136.9	2932.80 nanogram per milliliter Geometric Coefficient of Variation 75.6	9241.31 nanogram per milliliter Geometric Coefficient of Variation 52.1	—
Serum Concentrations of Mavrilimumab Day 169 (n=63, 73, 74)	348.97 nanogram per milliliter Geometric Coefficient of Variation 141.2	5282.37 nanogram per milliliter Geometric Coefficient of Variation 62.0	9178.47 nanogram per milliliter Geometric Coefficient of Variation 56.6	—

SECONDARY outcome

Timeframe: Day 1 to Day 169

Population: 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.

Immunogenicity assessment included determination of anti-drug (mavrilimumab) antibodies in serum samples. ADA detection measured by using electrochemiluminescence assays.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	Mavrilimumab 30 mg n=81 Participants 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 n=85 Participants 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 n=79 Participants 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.
Percentage of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit	2.5 percentage of participants	16.0 percentage of participants	3.5 percentage of participants	0.0 percentage of participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Mavrilimumab 30 mg

Serious events: 4 serious events

Other events: 41 other events

Deaths: 0 deaths

Mavrilimumab 100 mg

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

Mavrilimumab 150 mg

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=81 participants at risk 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.	Mavrilimumab 30 mg n=81 participants at risk 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 n=85 participants at risk 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 n=79 participants at risk 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.
Cardiac disorders Atrial tachycardia	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Cardiac disorders Supraventricular tachycardia	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Gastrointestinal disorders Dyspepsia	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Hepatobiliary disorders Cholelithiasis	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Infections and infestations Pneumonia	0.00% 0/81 • Baseline up to Day 169	1.2% 1/81 • Number of events 1 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/81 • Baseline up to Day 169	1.2% 1/81 • Number of events 1 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/81 • Baseline up to Day 169	1.2% 1/81 • Number of events 1 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.2% 1/81 • Number of events 1 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of the cervix	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	1.2% 1/85 • Number of events 1 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	1.3% 1/79 • Number of events 1 • Baseline up to Day 169
Reproductive system and breast disorders Cystocele	0.00% 0/81 • Baseline up to Day 169	1.2% 1/81 • Number of events 1 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	0.00% 0/79 • Baseline up to Day 169
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/81 • Baseline up to Day 169	0.00% 0/81 • Baseline up to Day 169	0.00% 0/85 • Baseline up to Day 169	1.3% 1/79 • Number of events 1 • Baseline up to Day 169

Other adverse events

Additional Information

Marius Albulescu, Associate Medical Director

MedImmune, LLC

Phone: 301-398-0000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Publication restrictions are in place

Restriction type: OTHER