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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01050998
First Posted: January 18, 2010
Last Update Posted: February 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
MedImmune Ltd
Information provided by (Responsible Party):
MedImmune LLC
  Purpose
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).

Condition Intervention Phase
Rheumatoid Arthritis Biological: Mavrilimumab 10 mg Biological: Mavrilimumab 30 mg Biological: Mavrilimumab 50 mg Biological: Mavrilimumab 100 mg Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 [ Time Frame: 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.

  • Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region [ Time Frame: Day 85 ]
    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.

  • Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 [ Time Frame: 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.

  • Percentage of Participants Who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region [ Time Frame: 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. DAS28 (ESR) response at Day 85 for the European and Japanese regions were reported.

  • Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 [ Time Frame: 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.

  • Percentage of Participants Who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region [ Time Frame: 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 =< 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.

  • Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 [ Time Frame: 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.

  • Percentage of Participants Who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region [ Time Frame: 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. DAS28 (ESR) response by EULAR category at Day 85 for the European and Japanese regions were reported.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Baseline up to Day 169 (follow-up) ]
    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.

  • Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 169 (follow-up) ]
    Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported.

  • Number of Participants With Abnormal Electrocardiogram (ECG) Results [ Time Frame: Baseline up to Day 169 (follow-up) ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 [ Time Frame: 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.

  • Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region [ Time Frame: 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. FEV1 and FVC at Day 85 for the European and Japanese regions were reported.

  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 [ Time Frame: Baseline and 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.

  • Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 [ Time Frame: Day 85 ]
    DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide.

  • Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region [ Time Frame: Day 85 ]
    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.

  • Change From Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 [ Time Frame: Baseline and Day 85 ]
    DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide.

  • Dyspnea Score at Day 85 [ Time Frame: 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.

  • Change From Baseline in Dyspnea Score at Day 85 [ Time Frame: Baseline and 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.

  • Categorized Dyspnea Score at Day 85 [ Time Frame: 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).

  • Oxygen Saturation Level at Day 85 [ Time Frame: Day 85 ]
    Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

  • Oxygen Saturation Level at Day 85 by Region [ Time Frame: Day 85 ]
    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.

  • Change From Baseline in Oxygen Saturation Level at Day 85 [ Time Frame: Baseline and Day 85 ]
    Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

  • Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 169 (follow-up) ]
    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).


Secondary Outcome Measures:
  • Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 [ Time Frame: Baseline and 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.

  • Change From Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region [ Time Frame: Baseline and 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. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported.

  • Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 [ Time Frame: 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.

  • Percentage of Participants Who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region [ Time Frame: 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. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported.

  • Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission [ Time Frame: Baseline up to Day 169 (follow-up) ]
    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 Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region [ Time Frame: Baseline up to Day 169 (follow-up) ]
    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.

  • Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission [ Time Frame: Baseline up to Day 169 ]
    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.

  • Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 [ Time Frame: 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).

  • Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region [ Time Frame: Day 85 ]
    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.

  • Number of Participants Who Achieved ACR Categorical Responses [ Time Frame: Day 85 ]
    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".

  • Continuous ACR (ACRn) Score [ Time Frame: Day 85 ]
    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.

  • Continuous ACR (ACRn) Score by Region [ Time Frame: Day 85 ]
    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.

  • Swollen and Tender Joint Count [ Time Frame: Day 85 ]
    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.

  • Swollen and Tender Joint Count by Region [ Time Frame: Day 85 ]
    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.

  • Physician Global Assessment of Disease Activity Score [ Time Frame: Day 85 ]
    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.

  • Physician Global Assessment of Disease Activity Score by Region [ Time Frame: Day 85 ]
    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.

  • Patient Global Assessment of Disease Activity Score [ Time Frame: Day 85 ]
    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.

  • Patient Global Assessment of Disease Activity Score by Region [ Time Frame: Day 85 ]
    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.

  • Patient Pain Assessment Score [ Time Frame: Day 85 ]
    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.

  • Patient Pain Assessment Score by Region [ Time Frame: Day 85 ]
    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.

  • Health Assessments Questionnaire-Disability Index (HAQ-DI) Score [ Time Frame: Day 85 ]
    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.

  • Health Assessments Questionnaire-Disability Index (HAQ-DI) Score by Region [ Time Frame: Day 85 ]
    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.

  • Health Assessments Questionnaire (HAQ) Pain Score [ Time Frame: Day 85 ]
    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.

  • Health Assessments Questionnaire (HAQ) Pain Score by Region [ Time Frame: Day 85 ]
    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.

  • Serum Concentration of C-Reactive Protein (CRP) [ Time Frame: Day 85 ]
    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.

  • Serum Concentration of C-Reactive Protein (CRP) by Region [ Time Frame: Day 85 ]
    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.

  • Serum Concentration of Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Day 85 ]
    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.

  • Serum Concentration of Erythrocyte Sedimentation Rate (ESR) by Region [ Time Frame: Day 85 ]
    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.

  • Serum Concentration of Rheumatoid Factor (RF) [ Time Frame: Day 85 ]
  • Serum Concentration of Anti-Citrullinated-Peptide-Antibody (ACPA) [ Time Frame: Day 85 ]
  • Number of Participants Who Had Additional Medications [ Time Frame: Baseline up to Day 169 ]
    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.

  • Number of Participants With Change in Methotrexate (MTX) and Corticosteroid (CST) Dose [ Time Frame: Baseline, Day 1 to 85, Day 86 to 169 ]
    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.

  • Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After First Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After First Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After First Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Maximum Observed Serum Concentration (Cmax) for Mavrilimumab After Last Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Time to Reach Maximum Observed Serum Concentration (Tmax) for Mavrilimumab After Last Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Mavrilimumab After Last Dose by Region [ Time Frame: 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 ]
    Data for European and Japanese regions were reported.

  • Terminal Phase Elimination Half-Life (t1/2) for Mavrilimumab After Last Dose by Region [ Time Frame: 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 ]
    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.

  • Accumulation Ratio for Mavrilimumab After Last Dose by Region [ Time Frame: 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 was calculated as ratio of AUCtau after last dose and AUCtau after first dose. Data for European and Japanese regions were reported.

  • Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab at Any Visit [ Time Frame: Day 1 up to Day 169 ]
    ADA detection measured by using electrochemiluminescence assays.


Enrollment: 516
Study Start Date: January 2010
Study Completion Date: July 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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.

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01050998


  Show 56 Study Locations
Sponsors and Collaborators
MedImmune LLC
MedImmune Ltd
Investigators
Study Director: Marius Albulescu MedImmune Ltd
  More Information

Additional Information:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01050998     History of Changes
Other Study ID Numbers: MI-CP219
First Submitted: January 15, 2010
First Posted: January 18, 2010
Results First Submitted: September 15, 2016
Results First Posted: February 16, 2017
Last Update Posted: February 16, 2017
Last Verified: December 2016

Keywords provided by MedImmune LLC:
Rheumatoid Arthritis
Mavrilimumab
CAM-3001

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs