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A Phase III Study of Abatacept (BMS-188667) in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Abatacept

Methotrexate

Placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Rheumatoid Arthritis (RA) for greater than 1 year from the time of initial diagnosis of RA. Participants must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Abatacept + Methotrexate

Placebo + Methotrexate

Abatacept + Methotrexate Open Label

Arm Description

Short Term: Abatacept was dosed by weight with participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. Participants continued treatment with methotrexate (MTX) either orally or parenterally at a minimum dose of 15 mg.

Short Term: Participants received a placebo solution intravenously and methotrexate at the dose employed prior to study enrollment and a minimum of 15 mg.

Open Label: Abatacept was dosed intravenously by weight at 10 mg/kg in the OL period under tiered dosing such that participants weighing < 60 kg received abatacept 500 mg; participants ≥ 60 kg and ≤ 100 kg received abatacept 750 mg; and participants > 100 kg received abatacept 1 g. MTX was continued at the dose used in the DB period.

Outcomes

Primary Outcome Measures

Number of American College of Rheumatology 20 (ACR 20) Responders at Day 169

ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) at Day 365

The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain dividied by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0. Clinically meaningful HAQ response was defined as an improvement of at least 0.3 units from baseline in HAQ DI.

Baseline and Mean Change From Baseline (BL) in Radiographic Erosion Score Results at Day 365

To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Change from baseline = Post-baseline - Baseline value

Participants With Deaths, Adverse Events (AEs) and SAEs in the Open-Label (OL) Period

AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

Participants With Hematology Values Meeting the Marked Abnormality Criteria in the OL Period

Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.

Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria in the OL Period

Participants With Electrolyte Values Meeting the Marked Abnormality Criteria in the OL Period

Sodium < 0.9 * LLN or > 1.05 * ULN or if BL < LLN then use < 0.95 * BL or > ULN or if BL > ULN then use >1.05 *BL or < LLN; Potassium: < 0.9 * LLN or > 1.1 * ULN or if BL < LLN then use < 0.9 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Chloride: < 0.9 * LLN or > 1.1 * ULN or if BL < LLN then use <0.9 * BL or >ULN or if BL > ULN then use > 1.1 * BL or < LLN; Calcium <0.8 * LLN or > 1.2 * ULN or if BL < LLN then use <0.67 * BL or > ULN or if BL > ULN then use > 1.3 * BL or < LLN.

Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting the Marked Abnormality Criteria in the OL Period

Glucose: < 65 mg/dL or > 220 mg/dL; Fasting Glucose: <0.8 * LLN or > 1.5 * ULN or if BL < LLN then use < 0.8 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Total protein: < 0.9 * LLN or 1.1 * ULN or if BL < LLN then use 0.9 * BL or > ULN or if BL > ULN then use 1.1 * BL or < LLN; Albumin: < 0.9 * LLN or if BL < LLN then use 0.75 * BL; Uric acid: > 1.5 * ULN or if BL > ULN then use > 2.0 * BL. All urinalysis abnormalities were defined as: if missing BL then use >= 2 or if value >=4, or if BL = 0 or 0.5 then use >= 2, or if BL = 1.0 then use >= 3, or if BL = 2.0 then use >=4.

Mean BL Immunoglobulins Over Time in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365, Day 729, and Day 1,093.

Mean Change From BL in Immunoglobulins in the OL Period

Participants With Immunogenicity to Abatacept in the Cumulative DB + OL Period

Participants with titers to abatacept in the DB and OL periods. Serum samples from abatacept-treated adult participants with active Rheumatoid Arthritis (RA) were screened for the presence of drug-specific antibodies using two validated direct-format enzyme-linked immunosorbent assays (ELISAs) to determine the presence of antibodies to abatacept and or CTLA4-T.

Number of Participants Experiencing Clinically Significant Changes in Vital Signs in the OL Period

Vital signs included body temperature, heart rate, and seated blood pressure. Clinically significant changes were defined as those that were not within the normal range for the participant.

Number of Participants Experiencing AEs of Special Interest in the OL Period

AEs were defined as any new untoward medical occurrence or worsening of a pre- existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest have been identified to be those which may be associated with the use of immunomodulatory agents or infusion of therapeutic proteins. Acute infusional AEs were defined as those that occurred within 1 hour after the start of the infusion.

Mean BL Hematocrit in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Participant Hematocrit in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL Platelet Count in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Participant Platelet Count in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL Hemoglobin, Total Protein, and Albumin in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Hemoglobin, Total Protein, and Albumin in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL White Blood Cells in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in White Blood Cells in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL Liver Function Parameters in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Liver Function Parameters in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL Select Laboratory Parameters in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Select Laboratory Parameters in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Mean BL Serum Electrolytes in the OL Period

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Mean Change From BL in Serum Electrolytes in the OL Period

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Secondary Outcome Measures

Mean Number of Tender Joints and Swollen Joints at DB BL

Mean DB BL Participant Physical Pain Assessment, Participant Global Assessment, and Physician Global Assessment

Participant physical pain assessment was determined at baseline on the Visual Analog Scale (VAS) of 0 mm to 100 mm where 0mm is no pain and 100mm is worst pain possible. The mean participant global assessment is a measure of overall disease burden and is a component of the ACR and evaluated using the VAS 100 mm. The physician global assessment is a measure of overall disease burden and is a component of the ACR and evaluated using the VAS 0mm to 100 mm with 0mm indicating no disease burden and 100mm indicating worse disease burden possible.

BL Rheumatoid Factor (RF) Status for Participants Continuing in the OL Period

This analysis determined whether participants in the OL period were RF positive or RF negative based on serum samples. A positive value for RF was > 20 IU/ml; a negative value for RF was ≤ 20 IU/mL.

ACR 20 Responders at Day 365

ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

ACR 20 Responders in the Double-Blind (DB) Period

ACR 50 Responders at Day 169

ACR 50 response requires a patient to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 50 response if the participant had ACR 50 observed for at least 2 consecutive study visits.

ACR 50 Responders at Day 365

ACR 50 Responders in the DB Period

ACR 70 Responders at Day 169

ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.

ACR 70 Responders at Day 365

ACR 70 Responders in the DB Period

Number of Participants Achieving Major Clinical Response By Day 365

A Major Clinical Response (MCR) is defined as maintenance of an ACR 70 response over a continuous 6-month period.

Mean BL and Disease Activity Score 28 (DAS-28; Erythrocyte Sedimentation Rate [ESR]) at Day 169 and Day 365

The DAS 28 is an assessment of disease activity measured on a visual analog scale (VAS)of 100 mm. The scale reports from 1 to 10, with increasing number indicating increasing extent of disease progression. Scores for disease activity are defined as high (>5.1); low (≤3.2); remission (<2.6). Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, Discontinuation Due to SAEs, AEs, Related AEs, or Discontinued Due to AEs in the DB Period

Mean DB BL and Mean Change From BL in Joint Space Narrowing (JSN) and Total Score (TS)

To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Change from baseline = Post-baseline - Baseline value.

Mean DB BL Physical Component Summary of Health-Related Quality of Life (SF-36)

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Adjusted Mean Change From BL in the Physical Component Summary of Health-Related Quality of Life (SF-36) in the DB Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Participants in the DB Period Achieving an Extended Major Clinical Response

An extended major clinical response (MCR) was defined as a continuous ACR 70 response over any nine month treatment period with study medications. ACR 70 response criteria requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score.

Mean BL DAS-28 C-Reactive Protein (CRP) and ESR in the DB Period

The mean baseline CRP and ESR in the DB period on Day 169 and Day 365 was evaluated for all treated participants. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Adjusted Mean Change From BL in DAS-28 CRP and ESR in the DB Period

The mean change from baseline in CRP and ESR in the DB period was evaluated for all treated participants. Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.

Mean BL Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period

The mean baseline sIL2-r in the DB period was evaluated from serum samples for all treated participants.

Mean Change From BL in Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period

The mean change from baseline in sIL2-r in the DB period was evaluated for all treated participants.

ACR Core Component: Mean Number of Tender Joints at All Post-BL Visits in the DB Period

Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

ACR Core Component: Mean Number of Swollen Joints at All Post-BL Visits in the DB Period

The mean number of swollen joints in the DB period was evaluated based on the swollen joint core component of the ACR scoring system where increasing score indicates increasing level of severity. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

ACR Core Component: Mean Participant Pain Assessment at All Post-BL Visits in the DB Period

Participant self-reported pain assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible.

ACR Core Component: Mean Participant Physical Function Assessment at All Post-BL Visits in the DB Period

ACR Core Component: Mean Participant Global Assessment at All Post-BL Visits in the DB Period

Participant self-reported global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing no pain and 100mm representing the most pain possible.

ACR Core Component: Mean Physician Global Assessment at All Post-BL Visits in the DB Period

Physician global RA assessment core component of the ACR scoring system where increasing score indicates increasing level of severity as indicated on a 100mm Visual Analog Scale (VAS) with 0mm representing very good global RA assessment and 100mm representing very poor global RA assessment.

ACR Core Component: Mean CRP at All Post-BL Visits in the DB Period

CRP core component of the ACR scoring system was evaluated from serum samples in which increasing levels indicate increasing level of disease.

Number of Participants Discontinuing in the DB Period

Participants that discontinued treatment during the DB period for any reason were evaluated after 6 months and 1 year of treatment.

Change From BL in Joint Narrowing Score (JSN), Erosion Score (ES), and Total Score (TS) by Category in the DB Period

To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Improvement=decreases from BL, stable=same as BL, worsening=increases from BL.

Participants Experiencing Clinically Significant Changes in Vital Signs in the DB Period

All changes in participant vital signs were monitored on each day of study drug administration prior to dosing and 60 minutes after dosing. Vital signs included body temperature, heart rate, and seated blood pressure. Clinical significance was defined as any change from baseline that resulted in a value outside the normal limits for the participant.

Participants Experiencing AEs of Special Interest in the DB Period

AEs were defined as any new untoward medical occurrence or worsening of a pre- existing medical condition which does not necessarily have a causal relationship with this treatment. AEs were identified as those which may be associated with the use of immunomodulatory agents or infusion of therapeutic proteins. Acute infusional AEs were defined as those that occurred within 1 hour after the start of the infusion.

Mean BL Individual Components of the HAQ DI at Day 169 and Day 365

Adjusted Mean Change From BL in Individual Components of the HAQ DI at Day 169

Adjusted Mean Change From BL in Individual Components of the HAQ DI at Day 365

Number of Participants With Immunogenicity to Abatacept in the DB Period

Participants with titers to abatacept in the DB period. Serum samples from abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using two validated direct-format enzyme-linked immunosorbent assays (ELISAs) to determine the presence of antibodies to abatacept and/or CTLA4-T.

Number of New Tender Joints and Number of New Swollen Joints in the DB Period

Tender joints and swollen joints are core components of the ACR 20, 50, and 70. The incidences of new tender joints and new swollen joints were evaluated in the DB period after 6 months and 1 year of treatment.

Number of Participants Experiencing a 100% Reduction in Tender Joints or 100% Reduction in Swollen Joints in the DB Period

Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria in the DB Period

Marked abnormality criteria were: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 c/uL; eosinophils: >0.750 * 10^3 c/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 c/uL/ >7.50 * 10^3 c/uL.

Number of Participants With Liver and Kidney Function Tests Meeting Marked Abnormality Criteria in the DB Period

Marked abnormality criteria were: Aspartate Aminotransferase (AST) >3 * ULN or if BL > ULN then use >4 *BL; Alanine Aminotransferase (ALT) >3 * ULN or if BL > ULN then use > 4 * BL; Creatinine > 1.5 * BL.

Mean BL ESR and CRP Levels in the OL Period

Mean baseline values are reported for each cohort at each time point.

Mean Change From BL in ESR in the OL Period

Serum samples were evaluated from study participants to determine the mean change from baseline in ESR values.

Participant RF Seroconversion in the OL Period

This analysis determined participant RF status (positive or RF negative) based on serum samples at each specified timepoint. A positive value for RF was > 20 IU/ml; a negative value for RF was ≤ 20 IU/mL.

Number of ACR 20 Responders in the DB and OL Periods

ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, CRP or ESR, and degree of disability in HAQ score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

Number of ACR 50 Responders in the DB and OL Periods

Number of ACR 70 Responders in the DB and OL Periods

ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, CRP or ESR, and degree of disability in HAQ score. A participant achieved a sustained ACR 70 response if the participant had ACR 70 observed for at least 2 consecutive study visits.

Number of Participants Continuing in the OL Period With DAS-28 Remission or Low DAS-28 Activity Over Time

The DAS 28 is a continuous measure evaluating extent of disease activity in RA, and is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, erythrocyte sedimentation rate (ESR) and participant assessment of disease activity measure on a visual analog scale (VAS) of 100 mm. The scale reports from 1 to 10, with increasing number indicating increasing extent of disease progression. Scores for disease activity are defined as high (> 5.1); low (≤ 3.2); remission (< 2.6).

Mean BL DAS-28 CRP Over Time for Participants Continuing in the OL Period

Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL in DAS-28 CRP Over Time for Participants Continuing in the OL Period

Change from baseline in participant were calculated at all study visits in the DB and OL periods.

Mean BL DAS-28 ESR Over Time in the OL Period

Mean baseline values are reported for each cohort at each time point. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL in DAS-28 ESR Over Time in the OL Period

Change from baseline in participant serum values of ESR were calculated at all study visits in the OL period.

Number of Participants Achieving HAQ Response Over Time for Participants Continuing in the OL Period

BL and Mean Change From BL in Radiographic Erosion, Joint Space Narrowing (JSN), and Total Scores (TS) in the OL Period

Change from baseline in the Genant-modified Sharp erosion score, JSN, TS were evaluated for all participants at the end of the OL period. The total Genant-modified Sharp score (TS) ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145).Higher scores indicated more damage. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean BL Physical Component Summary of the SF-36 by Visit in the OL Period

Mean Change From BL by Visit in the Physical Component Summary of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Mental Component Summary of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Mental Component Summary of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Physical Function Component of the SF-36 by Visit in the OL Period

Mean Change From BL by Visit in the Physical Function Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Role-Physical Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Role-Physical Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Bodily Pain Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Bodily Pain Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL General Health Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the General Health Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Social Functioning Component of the SF-36 by Visit in the OL Period

Mean Change From BL by Visit in the Social Functioning Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Role-Emotional Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Role-Emotional Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Vitality Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Vitality Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Mental Health Component of the SF-36 by Visit in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL by Visit in the Mental Health Component of the SF-36 in the OL Period

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Mean BL Fatigue in the OL Period

Mean baseline values are reported for each cohort at each time point using the VAS 100 mm where 0= no fatigue to 100 = the worst fatigue imaginable. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL in Fatigue in the OL Period

The mean change from baseline in fatigue was measured on the VAS 100 mm where 0= no fatigue to 100 = the worst fatigue imaginable.

Mean BL Sleep Quality in the OL Period

Mean baseline values are reported for each cohort at each time point using the Medical Outcomes Study Sleep scale (MOS-sleep [assesses the extent of sleep problems and measures six dimensions of sleep on a 12-item participant-reported measure]). An overall Sleep Problems Index (SPI) was generated as a summary measure of different types of sleep problems (sleep disturbance, sleep quantity, sleep adequacy, etc.). The score ranges from 0 to 100, with 0 = no problems with sleep and 100 = the most severe problems with sleep. The mean score of the SPI in a population with chronic conditions is 29.

Mean Change From BL in Sleep Quality in the OL Period

The mean change from baseline in sleep quality was assessed on the Medical Outcomes Study Sleep scale (MOS-sleep [assesses the extent of sleep problems and measures six dimensions of sleep on a 12-item participant-reported measure]). An overall Sleep Problems Index (SPI) was generated as a summary measure of different types of sleep problems (sleep disturbance, sleep quantity, sleep adequacy, etc.). The score ranges from 0 to 100, with 0 = no problems with sleep and 100 = the most severe problems with sleep. The mean score of the SPI in a population with chronic conditions is 29.

Mean BL Limitations on Activities of Daily Living in the OL Period

Mean baseline values are reported for each cohort at each time point. Activity limitation was measured by the number of days in the past 30 days a participant was unable to perform usual activities due to RA. Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean Change From BL in Limitations on Activities of Daily Living in the OL Period

The mean change from baseline in limitations on activities of daily living in the OL period. Activity limitation was measured by the number of days in the past 30 days a participant was unable to perform usual activities due to RA.

Mean BL Interleukin-6 (IL-6), SIL-2R, and Tumor Necrosis Alpha (TNF-Alpha) in the DB Period

Mean Change From BL in Interleukin-6 (IL-6), SIL-2R, and Tumor Necrosis Alpha (TNF-Alpha) in the DB Period

The mean change from baseline in potential biomarkers of disease (IL-6, SIL-3R, and TNF-Alpha were determined for all participants.

Mean Change From BL in RF in the DB Period

The mean change from baseline in participant rheumatoid factor was determined after 6 months and 1 year of treatment relative to baseline. Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Mean BL E-Selectin, SICAM-1, and MMP3 in the DB Period

Mean Change From BL in E-Selectin, SICAM-1, and MMP3 in the DB Period

The mean change from basline in particpant biomarkers of RA disease (E-Selectin, SICAM-1, and MMP3) after 6 months and 1 year of treatment, relative to baseline, were evaluated.

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) for the Day 365 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 365 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) for the Day 449 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 449 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) for the Day 533 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 533 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 617 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 617 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 729 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 729 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 813 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 813 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 897 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 897 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 981 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 981 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,093 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,093 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,177 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,177 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,261 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,261 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,345 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,345 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,457 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,457 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,625 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,625 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,821 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,821 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 1,989 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 1,989 for Participants Continuing in the OL Period

Mean BL HAQ-DI Score and HAQ-DI Individual Component Scores at BL (Day 0) of the Day 2,185 Cohort of Participants Continuing in the OL Period

Mean Change From BL in HAQ-DI Score and HAQ-DI Individual Component Scores at Day 2,185 for Participants Continuing in the OL Period

Full Information

NCT ID

NCT00048568

First Posted

November 2, 2002

Last Updated

October 26, 2011

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00048568

Brief Title

A Phase III Study of Abatacept (BMS-188667) in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

Official Title

A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study and Open-Label Study to Evaluate the Efficacy and Safety of Abatacept in Combination Therapy With Methotrexate Versus Methotrexate Alone in Subjects With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

Study Type

Interventional

2. Study Status

Record Verification Date

October 2011

Overall Recruitment Status

Completed

Study Start Date

December 2002 (undefined)

Primary Completion Date

October 2009 (Actual)

Study Completion Date

October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

5. Study Description

Brief Summary

Short Term: The purpose of this clinical research study is to learn if abatacept (BMS-188667) in combination with methotrexate is better than methotrexate alone in participants that have active rheumatoid arthritis and are not responding to methotrexate. The safety of this treatment will also be studied. Long Term Extension: The purpose of this amendment is to provide participants who have completed the initial 12-month double-blind treatment period the opportunity to receive open label treatment with active drug treatment until abatacept is approved in the local country or until clinical development has been discontinued.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1250 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Abatacept + Methotrexate

Arm Type

Experimental

Arm Description

Arm Title

Placebo + Methotrexate

Arm Type

Active Comparator

Arm Description

Short Term: Participants received a placebo solution intravenously and methotrexate at the dose employed prior to study enrollment and a minimum of 15 mg.

Arm Title

Abatacept + Methotrexate Open Label

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Abatacept

Other Intervention Name(s)

BMS-188667

Intervention Description

Intravenous (IV) Solution, - Weight Titered (500 mg < 60 kg); (750 mg 60-100 kg), )1 gram > 100 kg), Day 1, Day 15, Day 29; every 28 days thereafter, 1 year

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

MTX

Intervention Description

Tablets, Oral, >= 15 mg, weekly, 1 year

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

IV solution, Intravenous, D5W, Day 1, Day 15, Day 29; every 28 days thereafter, 1 year

Primary Outcome Measure Information:

Title

Number of American College of Rheumatology 20 (ACR 20) Responders at Day 169

Description

Time Frame

Day 169

Title

Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ) at Day 365

Description

Time Frame

Day 365

Title

Baseline and Mean Change From Baseline (BL) in Radiographic Erosion Score Results at Day 365

Description

Time Frame

BL (Day 0), Day 365

Title

Participants With Deaths, Adverse Events (AEs) and SAEs in the Open-Label (OL) Period

Description

Time Frame

Day 365 to Day 2,185

Title

Participants With Hematology Values Meeting the Marked Abnormality Criteria in the OL Period

Description

Time Frame

Day 365 to Day 2,185

Title

Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria in the OL Period

Description

Time Frame

Day 365 to Day 2,185

Title

Participants With Electrolyte Values Meeting the Marked Abnormality Criteria in the OL Period

Description

Time Frame

Day 365 to Day 2,185

Title

Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting the Marked Abnormality Criteria in the OL Period

Description

Time Frame

Day 365 to Day 2,185

Title

Mean BL Immunoglobulins Over Time in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365, Day 729, and Day 1,093.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093

Title

Mean Change From BL in Immunoglobulins in the OL Period

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093

Title

Participants With Immunogenicity to Abatacept in the Cumulative DB + OL Period

Description

Time Frame

Day 1 to Day 1,821

Title

Number of Participants Experiencing Clinically Significant Changes in Vital Signs in the OL Period

Description

Vital signs included body temperature, heart rate, and seated blood pressure. Clinically significant changes were defined as those that were not within the normal range for the participant.

Time Frame

Day 365 to Day 1,821. All changes in participant vital signs were monitored on each day of study drug administration prior to dosing and 60 minutes after dosing.

Title

Number of Participants Experiencing AEs of Special Interest in the OL Period

Description

Time Frame

Day 365 to Day 2,185

Title

Mean BL Hematocrit in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

Baseline (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Participant Hematocrit in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL Platelet Count in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Participant Platelet Count in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL Hemoglobin, Total Protein, and Albumin in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Hemoglobin, Total Protein, and Albumin in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL White Blood Cells in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in White Blood Cells in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL Liver Function Parameters in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Liver Function Parameters in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL Select Laboratory Parameters in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Select Laboratory Parameters in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean BL Serum Electrolytes in the OL Period

Description

Mean baseline values are those that are reported for each cohort at each time point on Day 365 to Day 2,185.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Title

Mean Change From BL in Serum Electrolytes in the OL Period

Description

All changes in participant laboratory parameters were monitored on each day of study drug administration.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,905, Day 1,989, Day 2,073, Day 2,185

Secondary Outcome Measure Information:

Title

Mean Number of Tender Joints and Swollen Joints at DB BL

Time Frame

BL (Day 0)

Title

Mean DB BL Participant Physical Pain Assessment, Participant Global Assessment, and Physician Global Assessment

Description

Time Frame

BL (Day 0)

Title

BL Rheumatoid Factor (RF) Status for Participants Continuing in the OL Period

Description

Time Frame

BL (Day 365)

Title

ACR 20 Responders at Day 365

Description

ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in HAQ score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

Time Frame

Day 365

Title

ACR 20 Responders in the Double-Blind (DB) Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR 50 Responders at Day 169

Description

Time Frame

Day 169

Title

ACR 50 Responders at Day 365

Description

Time Frame

Day 365

Title

ACR 50 Responders in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR 70 Responders at Day 169

Description

Time Frame

Day 169

Title

ACR 70 Responders at Day 365

Description

Time Frame

Day 365

Title

ACR 70 Responders in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

Number of Participants Achieving Major Clinical Response By Day 365

Description

A Major Clinical Response (MCR) is defined as maintenance of an ACR 70 response over a continuous 6-month period.

Time Frame

Day 1 to Day 365. Data were collected monthly during the first 6 months and then every other month (with the exception of Day 337) during the second 6 months of the DB period.

Title

Mean BL and Disease Activity Score 28 (DAS-28; Erythrocyte Sedimentation Rate [ESR]) at Day 169 and Day 365

Description

Time Frame

BL (Day 0), Day 169, Day 365, Day 169, Day 365

Title

Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, Discontinuation Due to SAEs, AEs, Related AEs, or Discontinued Due to AEs in the DB Period

Description

Time Frame

Day 1 to Day 365

Title

Mean DB BL and Mean Change From BL in Joint Space Narrowing (JSN) and Total Score (TS)

Description

Time Frame

BL (Day 0), Day 365

Title

Mean DB BL Physical Component Summary of Health-Related Quality of Life (SF-36)

Description

Time Frame

BL (Day 0), Day 169, Day 365

Title

Adjusted Mean Change From BL in the Physical Component Summary of Health-Related Quality of Life (SF-36) in the DB Period

Description

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Time Frame

BL (Day 0), Day 169, Day 365

Title

Participants in the DB Period Achieving an Extended Major Clinical Response

Description

Time Frame

Day 1 to Day 365

Title

Mean BL DAS-28 C-Reactive Protein (CRP) and ESR in the DB Period

Description

Time Frame

BL (Day 0), Day 169, Day 365

Title

Adjusted Mean Change From BL in DAS-28 CRP and ESR in the DB Period

Description

The mean change from baseline in CRP and ESR in the DB period was evaluated for all treated participants. Adjustment based on ANCOVA model with treatment as factor and baseline value as covariate.

Time Frame

BL (Day 0), Day 169, Day 365

Title

Mean BL Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period

Description

The mean baseline sIL2-r in the DB period was evaluated from serum samples for all treated participants.

Time Frame

BL (Day 0), Day 169, Day 365

Title

Mean Change From BL in Soluble Interleukin-2 Receptors (sIL2-r) in the DB Period

Description

The mean change from baseline in sIL2-r in the DB period was evaluated for all treated participants.

Time Frame

BL (Day 0), Day 169, Day 365

Title

ACR Core Component: Mean Number of Tender Joints at All Post-BL Visits in the DB Period

Description

Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean Number of Swollen Joints at All Post-BL Visits in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean Participant Pain Assessment at All Post-BL Visits in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean Participant Physical Function Assessment at All Post-BL Visits in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean Participant Global Assessment at All Post-BL Visits in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean Physician Global Assessment at All Post-BL Visits in the DB Period

Description

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

ACR Core Component: Mean CRP at All Post-BL Visits in the DB Period

Description

CRP core component of the ACR scoring system was evaluated from serum samples in which increasing levels indicate increasing level of disease.

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365

Title

Number of Participants Discontinuing in the DB Period

Description

Participants that discontinued treatment during the DB period for any reason were evaluated after 6 months and 1 year of treatment.

Time Frame

Day 1 to Day 169, Day 170 to Day 365

Title

Change From BL in Joint Narrowing Score (JSN), Erosion Score (ES), and Total Score (TS) by Category in the DB Period

Description

To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Improvement=decreases from BL, stable=same as BL, worsening=increases from BL.

Time Frame

BL (Day 0), Day 365

Title

Participants Experiencing Clinically Significant Changes in Vital Signs in the DB Period

Description

Time Frame

Day 1 to Day 365

Title

Participants Experiencing AEs of Special Interest in the DB Period

Description

AEs were defined as any new untoward medical occurrence or worsening of a pre- existing medical condition which does not necessarily have a causal relationship with this treatment. AEs were identified as those which may be associated with the use of immunomodulatory agents or infusion of therapeutic proteins. Acute infusional AEs were defined as those that occurred within 1 hour after the start of the infusion.

Time Frame

Day 1 to Day 365

Title

Mean BL Individual Components of the HAQ DI at Day 169 and Day 365

Description

Time Frame

BL (Day 0), Day 169, Day 365

Title

Adjusted Mean Change From BL in Individual Components of the HAQ DI at Day 169

Description

Time Frame

Day 169

Title

Adjusted Mean Change From BL in Individual Components of the HAQ DI at Day 365

Description

Time Frame

Day 365

Title

Number of Participants With Immunogenicity to Abatacept in the DB Period

Description

Time Frame

Day 1 to Day 365

Title

Number of New Tender Joints and Number of New Swollen Joints in the DB Period

Description

Time Frame

Day 169, Day 365

Title

Number of Participants Experiencing a 100% Reduction in Tender Joints or 100% Reduction in Swollen Joints in the DB Period

Time Frame

Day 169, Day 365

Title

Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria in the DB Period

Description

Time Frame

Day 1 to Day 365

Title

Number of Participants With Liver and Kidney Function Tests Meeting Marked Abnormality Criteria in the DB Period

Description

Time Frame

Day 1 to Day 365

Title

Mean BL ESR and CRP Levels in the OL Period

Description

Mean baseline values are reported for each cohort at each time point.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,989, Day 2,185

Title

Mean Change From BL in ESR in the OL Period

Description

Serum samples were evaluated from study participants to determine the mean change from baseline in ESR values.

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 1,989, Day 2,185

Title

Participant RF Seroconversion in the OL Period

Description

Time Frame

Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821, Day 2,185

Title

Number of ACR 20 Responders in the DB and OL Periods

Description

ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, CRP or ESR, and degree of disability in HAQ score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

Time Frame

Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,083, Day 1,177, Day 1,261, Day 1,345, Day 1,497, Day 1,625, Day 1,821

Title

Number of ACR 50 Responders in the DB and OL Periods

Description

Time Frame

Title

Number of ACR 70 Responders in the DB and OL Periods

Description

ACR 70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five parameters: physician global assessment of disease, patient global assessment of disease, patient assessment of pain, CRP or ESR, and degree of disability in HAQ score. A participant achieved a sustained ACR 70 response if the participant had ACR 70 observed for at least 2 consecutive study visits.

Time Frame

Title

Number of Participants Continuing in the OL Period With DAS-28 Remission or Low DAS-28 Activity Over Time

Description

Time Frame

Title

Mean BL DAS-28 CRP Over Time for Participants Continuing in the OL Period

Description

Time-matched BL (Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Time Frame

BL(Day 0), Day 15, Day 29,Day 57,Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,083, Day 1,177, Day 1,261, Day 1,345, Day 1,497, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Mean Change From BL in DAS-28 CRP Over Time for Participants Continuing in the OL Period

Description

Change from baseline in participant were calculated at all study visits in the DB and OL periods.

Time Frame

BL(Day 0),Day 15,Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 225, Day 281, Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,083, Day 1,177, Day 1,261, Day 1,345, Day 1,497, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Mean BL DAS-28 ESR Over Time in the OL Period

Description

Time Frame

BL (Day 0), Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,083, Day 1,177, Day 1,261, Day 1,345, Day 1,497, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Mean Change From BL in DAS-28 ESR Over Time in the OL Period

Description

Change from baseline in participant serum values of ESR were calculated at all study visits in the OL period.

Time Frame

BL (Day 0), Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,083, Day 1,177, Day 1,261, Day 1,345, Day 1,497, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Number of Participants Achieving HAQ Response Over Time for Participants Continuing in the OL Period

Description

Time Frame

Title

BL and Mean Change From BL in Radiographic Erosion, Joint Space Narrowing (JSN), and Total Scores (TS) in the OL Period

Description

Time Frame

BL (Day 0), Day 365, Day 729, Day 1,093, Day 1,457, Day 1,821

Title

Mean BL Physical Component Summary of the SF-36 by Visit in the OL Period

Description

Time Frame

BL (Day 0), Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,093, Day 1,177, Day 1,261, Day 1,345, Day 14,57, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Mean Change From BL by Visit in the Physical Component Summary of the SF-36 in the OL Period

Description

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.

Time Frame

BL (Day 0), Day 365, Day 449, Day 533, Day 617, Day 729, Day 813, Day 897, Day 981, Day 1,093, Day 1,177, Day 1,261, Day 1,345, Day 14,57, Day 1,625, Day 1,821, Day 1,989, Day 2,185

Title

Mean BL Mental Component Summary of the SF-36 by Visit in the OL Period

Description

The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of > 3 points were considered clinically meaningful.Time-matched BL(Day 0) values and post-BL vales were presented for each post-BL visit and represent only that cohort of participants with measurements available at that post-BL assessment.

Time Frame