A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Efficacy and Safety of CAM-3001 in Subjects With Rheumatoid Arthritis

The primary objectives of this study is to assess the safety, tolerability and efficacy of multiple doses of the mavrilimumab (CAM-3001) administered subcutaneously in subjects with moderately active Rheumatoid Arthritis (RA).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Mavrilimumab 10 mg; Biological: Mavrilimumab 30 mg; Biological: Mavrilimumab 50 mg; Biological: Mavrilimumab 100 mg; Other: Placebo

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of multiple doses of the mavrilimumab (CAM-3001) (10 milligram [mg], 30 mg, 50 mg, and 100 mg) administered subcutaneously in adult subjects with moderately active RA.

• Study Type: Interventional
• Enrollment (Actual): 516
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Varna, Bulgaria
    • Research Site
• Czechia
  • Bruntal, Czechia
    • Research Site
  • Ostrava - Trebovice, Czechia
    • Research Site
  • Praha 2, Czechia
    • Research Site
  • Praha 4, Czechia
    • Research Site
  • Praha 4 - Nusle, Czechia
    • Research Site
  • Uherske Hradiste, Czechia
    • Research Site
  • Zlin, Czechia
    • Research Site
• Estonia
  • Tallinn, Estonia
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
  • Sopron, Hungary
    • Research Site
  • Zalaegerszeg, Hungary
    • Research Site
• Japan
  • Chiba-shi, Japan
    • Research Site
  • Chiyoda-ku, Japan
    • Research Site
  • Fukui-shi, Japan
    • Research Site
  • Fukuoka-shi, Japan
    • Research Site
  • Goshogawara-shi, Japan
    • Research Site
  • Hamamatsu-shi, Japan
    • Research Site
  • Iizuka-shi, Japan
    • Research Site
  • Kagoshima-shi, Japan
    • Research Site
  • Kasama-shi, Japan
    • Research Site
  • Kitakyushu-shi, Japan
    • Research Site
  • Nagano-Shi, Japan
    • Research Site
  • Nagoya-shi, Japan
    • Research Site
  • Okayama-shi, Japan
    • Research Site
  • Omura-shi, Japan
    • Research Site
  • Sagamihara-shi, Japan
    • Research Site
  • Sasebo-shi, Japan
    • Research Site
  • Shinjuku-ku, Japan
    • Research Site
• Latvia
  • Liepaja, Latvia
    • Research Site
  • Riga, Latvia
    • Research Site
  • Valmiera, Latvia
    • Research Site
• Lithuania
  • Klaipeda, Lithuania
    • Research Site
  • Vilnius, Lithuania
    • Research Site
• Poland
  • Bialystok, Poland
    • Research Site
  • Bydgoszcz, Poland
    • Research Site
  • Katowice, Poland
    • Research Site
  • Legnica, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Poznan, Poland
    • Research Site
  • Torun, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
• Romania
  • Bucuresti, Romania
    • Research Site
  • Ploiesti, Romania
    • Research Site
  • Targu Mures, Romania
    • Research Site
• Russian Federation
  • Barnaul, Russian Federation
    • Research Site
  • Kazan, Russian Federation
    • Research Site
  • Kemerovo, Russian Federation
    • Research Site
  • Novosibirsk, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
  • Yaroslavl, Russian Federation
    • Research Site
• Ukraine
  • Donetsk, Ukraine
    • Research Site
  • Kiev, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 through 80 years (20 to 75 years in Japan)
• Written consent
• Diagnosis of adult onset Rheumatoid Arthritis (RA) of at least 3 months duration as defined by the 1987 American College of Rheumatology (ACR) classification criteria (Arnett et al, 1988)
• Treatment with methotrexate at a stable and tolerated doses
• Positive anti-cyclic citrullinated peptide (CCP) immuno-globulin G antibodies (more than [>] 5 international unit per milliliter [IU/mL]) and/or rheumatoid factor (RF >14 IU/mL) at screening
• Received more than or equal to (>=) 5 milligram (mg) per week folic acid as a single or divided dose during the study.

Exclusion Criteria:

• A rheumatic autoimmune disease other than RA
• A history of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder
• Subjects at a high risk of infection
• Subjects (male and female) of reproductive potential who are not willing to use contraception from screening through the end date of the trial
• History of methotrexate or any drug-induced lung fibrosis or pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mavrilimumab 10 mg; Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.	Biological: Mavrilimumab 10 mg; Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks.; Other Names: CAM-3001
EXPERIMENTAL: Mavrilimumab 30 mg; Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.	Biological: Mavrilimumab 30 mg; Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks.; Other Names: CAM-3001
EXPERIMENTAL: Mavrilimumab 50 mg; Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.	Biological: Mavrilimumab 50 mg; Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks.; Other Names: CAM-3001
EXPERIMENTAL: Mavrilimumab 100 mg; Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.	Biological: Mavrilimumab 100 mg; Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks.; Other Names: CAM-3001
PLACEBO_COMPARATOR: Placebo; Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.	Other: Placebo; Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85	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.	Day 85
Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region	DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. DAS28 (CRP) response at Day 85 for the European and Japanese regions were reported.	Day 85
Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85	DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85.	Day 85
Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region	DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. DAS28 (ESR) response at Day 85 for the European and Japanese regions were reported.	Day 85
Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85	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.	Day 85
Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region	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 =< 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. DAS28 (CRP) response by EULAR category at Day 85 for the European and Japanese regions were reported.	Day 85
Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85	DAS28 (ESR) 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 (ESR) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (ESR) >=3.2 to =< 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (ESR) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (ESR) >5.1.	Day 85
Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region	DAS28 (ESR) 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 (ESR) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (ESR) >=3.2 to =< 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (ESR) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (ESR) >5.1. DAS28 (ESR) response by EULAR category at Day 85 for the European and Japanese regions were reported.	Day 85
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up Day 169 that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to Day 169 (follow-up)
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)	Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported.	Baseline up to Day 169 (follow-up)
Number of Participants With Abnormal Electrocardiogram (ECG) Results	12-lead ECG was recorded and corrected QT (QTc) interval was measured with the participant in a rested supine position for at least 10 minutes. Any ECG abnormality deemed clinically significant as per investigator's discretion were reported.	Baseline up to Day 169 (follow-up)
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85	FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.	Day 85
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region	FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC at Day 85 for the European and Japanese regions were reported.	Day 85
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85	FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.	Baseline and Day 85
Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85	DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide.	Day 85
Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region	DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported.	Day 85
Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85	DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide.	Baseline and Day 85
Dyspnea Score at Day 85	Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing.	Day 85
Change From Baseline in Dyspnea Score at Day 85	Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing.	Baseline and Day 85
Categorized Dyspnea Score at Day 85	Modified Borg dyspnea scale is a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The modified BORG dyspnea scale was categorized as - no/slight (0 to 2), moderate (3 and 4), severe (5 and 6) and very severe breathlessness (7 and above).	Day 85
Oxygen Saturation Level at Day 85	Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.	Day 85
Oxygen Saturation Level at Day 85 by Region	Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported.	Day 85
Change From Baseline in Oxygen Saturation Level at Day 85	Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.	Baseline and Day 85
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)	Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, reticulocytes, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration); serum chemistry (creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamyl transferase, CRP, ESR, albumin, total cholesterol, triglycerides, rheumatoid factor and anti-cyclic citrullinated peptide antibodies); urinalysis (albumin, glucose, protein, blood, nitrite).	Baseline up to Day 169 (follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission.	Baseline and Day 85
Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported.	Baseline and Day 85
Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score.	Day 85
Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported.	Day 85
Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score.	Baseline up to Day 169 (follow-up)
Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. Time to response for DAS28 (CRP) and DAS28 (ESR) by region were reported. Time to remission for DAS28 (CRP) and DAS28 (ESR) by region were not analyzed because time to remission for the overall study population could not be achieved.	Baseline up to Day 169 (follow-up)
Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission	DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. Expected duration of response (DOR) was calculated as response rate (in percentage) multiplied by mean DOR (in days) by using Weibull Model. Duration of DAS28 (CRP) and DAS28 (ESR) remission were not analyzed because very few participants achieved remission in the overall study population.	Baseline up to Day 169
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85	ACR20, ACR50, and ACR70, were defined as greater than or equal to (>=) 20 percent (%),>=50%, or >=70% improvement, respectively, in: swollen joint count and tender joint count and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).	Day 85
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region	ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Data for the European and Japanese regions were reported.	Day 85
Number of Participants Who Achieved ACR Categorical Responses	ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. ACR responses were categorized as "No response", "ACR20 but not ACR50", "ACR50 but not ACR70", and "ACR70".	Day 85
Continuous ACR (ACRn) Score	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.	Day 85
Continuous ACR (ACRn) Score by Region	ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. Data for European and Japanese regions were reported.	Day 85
Swollen and Tender Joint Count	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.	Day 85
Swollen and Tender Joint Count by Region	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. Data for the European and Japanese regions were reported.	Day 85
Physician Global Assessment of Disease Activity Score	Physician Global Assessment of Arthritis was measured on a 0 to 10 centimeter (cm) Visual Analogue Scale (VAS), where 0 cm = very good and 10 cm = very bad.	Day 85
Physician Global Assessment of Disease Activity Score by Region	Physician Global Assessment of Arthritis was measured on a 0 to 10 cm VAS, where 0 cm = very good and 10 cm = very bad. Data for European and Japanese regions were reported.	Day 85
Patient Global Assessment of Disease Activity Score	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.	Day 85
Patient Global Assessment of Disease Activity Score by Region	Participants responded to a question, "Considering all the ways your arthritis affects you, how are you feeling today?" by using a 0 - 100 mm VAS, where 0 = very well and 100 = very poorly. Data for European and Japanese regions were reported.	Day 85
Patient Pain Assessment Score	Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.	Day 85
Patient Pain Assessment Score by Region	Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain. Data for European and Japanese regions were reported.	Day 85
Health Assessments Questionnaire-Disability Index (HAQ-DI) Score	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 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 0-3 where 0 = least difficulty and 3 = extreme difficulty.	Day 85
Health Assessments Questionnaire-Disability Index (HAQ-DI) Score by Region	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 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 0-3 where 0 = least difficulty and 3 = extreme difficulty. Data for European and Japanese regions were reported.	Day 85
Health Assessments Questionnaire (HAQ) Pain Score	Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain.	Day 85
Health Assessments Questionnaire (HAQ) Pain Score by Region	Participants were asked to assess the severity of pain in the past week on a 100 VAS with 0 being no pain and 100 being severe pain. Data for European and Japanese regions were reported.	Day 85
Serum Concentration of C-Reactive Protein (CRP)	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.	Day 85
Serum Concentration of C-Reactive Protein (CRP) by Region	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. Data for European and Japanese regions were reported.	Day 85
Serum Concentration of Erythrocyte Sedimentation Rate (ESR)	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.	Day 85
Serum Concentration of Erythrocyte Sedimentation Rate (ESR) by Region	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. Data for European and Japanese regions were reported.	Day 85
Serum Concentration of Rheumatoid Factor (RF)		Day 85
Serum Concentration of Anti-Citrullinated-Peptide-Antibody (ACPA)		Day 85
Number of Participants Who Had Additional Medications	Additional medication included concomitant medication (medication used for purposes other than managing rheumatoid arthritis [RA]) and RA medication (for managing RA). Number of participants who used concomitant medication and RA medication was reported by anatomical therapeutic chemical (ATC) classification system.	Baseline up to Day 169
Number of Participants With Change in Methotrexate (MTX) and Corticosteroid (CST) Dose	Participants received MTX at stable and tolerated dose during baseline were categorized as "low dose (<12.5 mg per week [mg/wk])", "medium dose (>=12.5 - <20 mg/wk)", and "high dose (>=20 mg/wk)". Participants received oral CST at stable dose during baseline were categorized as "low dose (<5 mg/day)", and "high dose (>=5 mg/day)". Change in MTX and CST dose from baseline between Day 1-85 and Day 86-169 were categorized as follows: 'Increased', 'no change' and 'decreased'. Participants were counted once with dose increases counted first, followed by no change and then dose decreases.	Baseline, Day 1 to 85, Day 86 to 169
Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After First Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After First Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After First Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After Last Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After Last Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After Last Dose by Region	Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Terminal Phase Elimination Half-Life (t1/2) for Mavrilimumab After Last Dose by Region	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Accumulation Ratio for Mavrilimumab After Last Dose by Region	Accumulation ratio was calculated as ratio of AUCtau after last dose and AUCtau after first dose. Data for European and Japanese regions were reported.	Blood samples were collected at pre-dose on Days 1, 4, 8, 15, 29, 57, and 85 as well as during follow up on Days 88, 99, 113 and 169
Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit	ADA detection measured by using electrochemiluminescence assays.	Day 1 up to Day 169

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: MedImmune Ltd

Publications and helpful links

General Publications

• Burmester GR, Weinblatt ME, McInnes IB, Porter D, Barbarash O, Vatutin M, Szombati I, Esfandiari E, Sleeman MA, Kane CD, Cavet G, Wang B, Godwood A, Magrini F; EARTH Study Group. Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis. 2013 Sep 1;72(9):1445-52. doi: 10.1136/annrheumdis-2012-202450. Epub 2012 Dec 12.

Helpful Links

• CAM-3001_CP-219_Redacted_4Mar13

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 5, 2010
• Primary Completion (ACTUAL): June 9, 2011
• Study Completion (ACTUAL): July 27, 2012

Study Registration Dates

• First Submitted: January 15, 2010
• First Submitted That Met QC Criteria: January 15, 2010
• First Posted (ESTIMATE): January 18, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2018
• Last Update Submitted That Met QC Criteria: March 23, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Mavrilimumab; CAM-3001
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Immunologic Factors; Antibodies, Monoclonal; Mavrilimumab
• Other Study ID Numbers: MI-CP219