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Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Abatacept

Methotrexate

Abatacept placebo

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

Key Inclusion Criteria:

Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
Onset of persistent symptoms ≤ 2 years prior to screening
Positive test result for anticyclic citrullinated peptides 2
Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
Biologic naive, including no treatment with an investigational biologic prior to screening
Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
Able to undergo magnetic resonance imaging

Key Exclusion Criteria:

Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
Scheduled for or anticipating joint replacement surgery
Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
History of malignancy in the last 5 years
Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
At risk for tuberculosis
Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Abatacept, 125 mg, plus methotrexate, 2.5 mg

Methotrexate, 2.5 mg, plus abatacept placebo

Abatacept, 125 mg, plus methotrexate placebo

Arm Description

Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period

Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period

Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

DAS28-CRP remission defined as <2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Secondary Outcome Measures

Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population

TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18

TP=treatment period; WP=withdrawal period. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18

TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity. TJC is assessed and recorded at each visit, with no swelling=0, swelling=1. SJC is assessed through identification of joints that are painful under pressure or to passive motion. TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1. Higher score indicates greater affection due to disease activity.

Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time

TP=treatment period; WP=withdrawal period. The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SJC is assessed and recorded at each visit, with no swelling=0, swelling=1 (higher score indicates greater swelling). TJC is assessed at each visit through identification of joints that are painful under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity)..

Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time

HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.

Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time

The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.

Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)

TP=treatment period; WP=withdrawal period. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.

Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)

TP=treatment period; WP=withdrawal period. Change from Baseline=Postbaseline-baseline value. MRI was used to assess joint damage progression at Months 6, 12, and 18. If >20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing. If ≤20% of joints had a missing score for a parameter, the MRI score for that parameter from the missing joints was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline. MRI total score ranged from 0 (best outcome) to 4 (worst outcome). A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized patients at 5 points. The hand/wrist assessed to have more synovitis was selected initially and used for all subsequent evaluations. The MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis.

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period

Adverse Events (AEs) of Interest During the Treatment Period

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period

Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX). Criteria for marked abnormality: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.

Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12

WP=withdrawal period. Remission defined as DAS28-CRP<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.). Percentage= number of participants with remission divided by number of participants who were analyzed (all treated participants who were in remission at end of treatment period and entered the Withdrawal Period)

Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Includes data up to last active dose date +56 days if the participant discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for participants discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for participants who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for participants entering the Re-exposure Period.

Adverse Events (AEs) of Interest During the Withdrawal Period

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period. Treatment groups represent treatment received during the Treatment Period.

Adverse Events (AEs) of Interest During the Re-exposure Period

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase (GGT) (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.

Full Information

NCT ID

NCT01142726

First Posted

June 3, 2010

Last Updated

December 9, 2015

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01142726

Brief Title

Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

Official Title

A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

December 2010 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.

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

511 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Abatacept, 125 mg, plus methotrexate, 2.5 mg

Arm Type

Active Comparator

Arm Description

Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period

Arm Title

Methotrexate, 2.5 mg, plus abatacept placebo

Arm Type

Active Comparator

Arm Description

Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period

Arm Title

Abatacept, 125 mg, plus methotrexate placebo

Arm Type

Active Comparator

Arm Description

Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period

Intervention Type

Drug

Intervention Name(s)

Abatacept

Other Intervention Name(s)

Orencia, BMS 188667

Intervention Description

Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

Rheumatrex

Intervention Description

Tablets, oral, 2.5 mg, once weekly, 12 months

Intervention Type

Drug

Intervention Name(s)

Abatacept placebo

Intervention Description

Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months

Intervention Type

Drug

Intervention Name(s)

Methotrexate placebo

Intervention Description

Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

Description

Time Frame

Randomization to Months 12 and 18

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18

Description

Time Frame

Randomization to Months 12 and 18

Title

Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population

Description

Time Frame

Randomization to Month 24

Title

Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18

Description

Time Frame

Baseline to Month 18

Title

Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18

Description

Time Frame

Randomization to Month 18

Title

Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time

Description

Time Frame

Randomization to Month 18

Title

Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time

Description

Time Frame

Randomization to Month 24

Title

Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time

Description

Time Frame

Randomization to Month 18

Title

Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)

Description

Time Frame

Randomization to Months 6, 12, and 18

Title

Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)

Description

Time Frame

Randomization to Month 18

Title

Description

Time Frame

Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period

Title

Adverse Events (AEs) of Interest During the Treatment Period

Description

Time Frame

Day 1 to 56 days following last dosing day (Day 365)

Title

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period

Description

Time Frame

Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)

Title

Description

Time Frame

End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)

Title

Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period

Description

Time Frame

Randomization to Month 24

Title

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)

Description

Time Frame

Day 1 to 56 days post last dose in the study, up to Month 30

Title

Adverse Events (AEs) of Interest During the Withdrawal Period

Description

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period. Treatment groups represent treatment received during the Treatment Period.

Time Frame

Last dose in TP + 57 days, up to Month 24

Title

Adverse Events (AEs) of Interest During the Re-exposure Period

Description

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AEs of special interest are events potentially associated with the drug or disease under study. Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.

Time Frame

First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days

Title

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period

Description

Time Frame

Last dose in TP + 57 days, up to Month 24

Title

Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period

Description

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN, or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.

Time Frame

Start of re-exposure period to 56 days post last dose, up to Month 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening Onset of persistent symptoms ≤ 2 years prior to screening Positive test result for anticyclic citrullinated peptides 2 Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit Biologic naive, including no treatment with an investigational biologic prior to screening Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks Able to undergo magnetic resonance imaging Key Exclusion Criteria: Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus) Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization Scheduled for or anticipating joint replacement surgery Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator History of malignancy in the last 5 years Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection At risk for tuberculosis Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Rheumatology Associates Of North Alabama, P.C.

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35801

Country

United States

Facility Name

St. Joseph'S Mercy Clinic

City

Hot Springs

State/Province

Arkansas

ZIP/Postal Code

71913

Country

United States

Facility Name

Sarasota Arthritis Research Center

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34239

Country

United States

Facility Name

Coeur D'Alene Arthrit Clin

City

Coeur D Alene

State/Province

Idaho

ZIP/Postal Code

83814

Country

United States

Facility Name

Johns Hopkins University Division Of Rheumatology

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21224

Country

United States

Facility Name

Clinical Pharmacology Study Group

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01605

Country

United States

Facility Name

Arthritis Associates Of Mississippi

City

Jackson

State/Province

Mississippi

ZIP/Postal Code

39202

Country

United States

Facility Name

Physician Research Collaboration, Llc

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

Facility Name

Piedmont Rheumatology, Pa

City

Hickory

State/Province

North Carolina

ZIP/Postal Code

28602

Country

United States

Facility Name

Carolina Arthritis Associates

City

Wilmington

State/Province

North Carolina

ZIP/Postal Code

28401

Country

United States

Facility Name

Metrohealth Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44109

Country

United States

Facility Name

Isam A. Diab, Md

City

Middleburg

State/Province

Ohio

ZIP/Postal Code

44130

Country

United States

Facility Name

Alan J. Kivitz, Md, Cpi

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

Mitchell C. Feinman, Md

City

Orangeburg

State/Province

South Carolina

ZIP/Postal Code

29118

Country

United States

Facility Name

Kurt Oelke, Md

City

Glendale

State/Province

Wisconsin

ZIP/Postal Code

53217

Country

United States

Facility Name

Local Institution

City

Cairns

State/Province

Queensland

ZIP/Postal Code

4870

Country

Australia

Facility Name

Local Institution

City

Maroochydore

State/Province

Queensland

ZIP/Postal Code

4558

Country

Australia

Facility Name

Local Institution

City

Woodville

State/Province

South Australia

ZIP/Postal Code

5011

Country

Australia

Facility Name

Local Institution

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

Local Institution

City

Malvern

State/Province

Victoria

ZIP/Postal Code

3144

Country

Australia

Facility Name

Local Institution

City

Victoria Park

State/Province

Western Australia

ZIP/Postal Code

6100

Country

Australia

Facility Name

Local Institution

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Local Institution

City

Kortrijk

ZIP/Postal Code

8500

Country

Belgium

Facility Name

Local Institution

City

Merksem

ZIP/Postal Code

2170

Country

Belgium

Facility Name

Local Institution

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 4N1

Country

Canada

Facility Name

Local Institution

City

Laval

State/Province

Quebec

ZIP/Postal Code

H7T 2P5

Country

Canada

Facility Name

Local Institution

City

Hjorring

ZIP/Postal Code

9800

Country

Denmark

Facility Name

Local Institution

City

Helsinki

ZIP/Postal Code

00290

Country

Finland

Facility Name

Local Institution

City

Tampere

ZIP/Postal Code

33521

Country

Finland

Facility Name

Local Institution

City

Chambray Les Tours

ZIP/Postal Code

37170

Country

France

Facility Name

Local Institution

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

Local Institution

City

Paris Cedex 14

ZIP/Postal Code

75679

Country

France

Facility Name

Local Institution

City

Poitiers

ZIP/Postal Code

86021

Country

France

Facility Name

Local Institution

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Local Institution

City

Berlin

ZIP/Postal Code

14059

Country

Germany

Facility Name

Local Institution

City

Hildesheim

ZIP/Postal Code

31134

Country

Germany

Facility Name

Local Institution

City

Muenchen

ZIP/Postal Code

80336

Country

Germany

Facility Name

Local Institution

City

Muenchen

ZIP/Postal Code

80639

Country

Germany

Facility Name

Local Institution

City

Muenchen

ZIP/Postal Code

81541

Country

Germany

Facility Name

Local Institution

City

Ancona

ZIP/Postal Code

60055

Country

Italy

Facility Name

Local Institution

City

Siena

ZIP/Postal Code

53100

Country

Italy

Facility Name

Local Institution

City

Daegu

ZIP/Postal Code

705-718

Country

Korea, Republic of

Facility Name

Local Institution

City

Daejeon

ZIP/Postal Code

302-799

Country

Korea, Republic of

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

133-791

Country

Korea, Republic of

Facility Name

Local Institution

City

Seoul

ZIP/Postal Code

137-701

Country

Korea, Republic of

Facility Name

Local Institution

City

Metepec

State/Province

Estado De Mexico

ZIP/Postal Code

52140

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44500

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44690

Country

Mexico

Facility Name

Local Institution

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64020

Country

Mexico

Facility Name

Local Institution

City

Merida

State/Province

Yucatan

ZIP/Postal Code

97000

Country

Mexico

Facility Name

Local Institution

City

Chihuahua

ZIP/Postal Code

31000

Country

Mexico

Facility Name

Local Institution

City

Queretaro

ZIP/Postal Code

76178

Country

Mexico

Facility Name

Local Institution

City

San Luis Potosi

ZIP/Postal Code

78240

Country

Mexico

Facility Name

Local Institution

City

Lublin

ZIP/Postal Code

20-954

Country

Poland

Facility Name

Local Institution

City

Poznan

ZIP/Postal Code

60-218

Country

Poland

Facility Name

Local Institution

City

Torun

ZIP/Postal Code

87100

Country

Poland

Facility Name

Local Institution

City

Warszawa

ZIP/Postal Code

01-157

Country

Poland

Facility Name

Local Institution

City

Warszawa

ZIP/Postal Code

01-868

Country

Poland

Facility Name

Local Institution

City

Wroc#aw

ZIP/Postal Code

50-088

Country

Poland

Facility Name

Local Institution

City

Moscow

ZIP/Postal Code

117049

Country

Russian Federation

Facility Name

Local Institution

City

Moscow

ZIP/Postal Code

129327

Country

Russian Federation

Facility Name

Local Institution

City

Tver

ZIP/Postal Code

170036

Country

Russian Federation

Facility Name

Local Institution

City

Kempton Park

State/Province

Gauteng

ZIP/Postal Code

1619

Country

South Africa

Facility Name

Local Institution

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0083

Country

South Africa

Facility Name

Local Institution

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0084

Country

South Africa

Facility Name

Local Institution

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0181

Country

South Africa

Facility Name

Local Institution

City

Durban

State/Province

Kwa Zulu Natal

ZIP/Postal Code

4001

Country

South Africa

Facility Name

Local Institution

City

Panorama

State/Province

Western Cape

ZIP/Postal Code

7500

Country

South Africa

Facility Name

Local Institution

City

Goteborg

ZIP/Postal Code

413 45

Country

Sweden

Facility Name

Local Institution

City

Linkoping

ZIP/Postal Code

581 85

Country

Sweden

Facility Name

Local Institution

City

Malmo

ZIP/Postal Code

205 02

Country

Sweden

Facility Name

Local Institution

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Local Institution

City

Uppsala

ZIP/Postal Code

751 85

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

35172859

Citation

Ahmad HA, Baker JF, Conaghan PG, Emery P, Huizinga TWJ, Elbez Y, Banerjee S, Ostergaard M. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022 Feb 16;24(1):47. doi: 10.1186/s13075-022-02735-8.

Results Reference

derived

PubMed Identifier

31819995

Citation

Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.

Results Reference

derived

PubMed Identifier

31278695

Citation

Ahmad HA, Baker JF, Ostergaard M, Ye J, Emery P, Conaghan PG. Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial. Adv Ther. 2019 Sep;36(9):2384-2393. doi: 10.1007/s12325-019-01020-6. Epub 2019 Jul 5.

Results Reference

derived

PubMed Identifier

30997151

Citation

Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Maldonado MA, Huizinga TW. Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study. RMD Open. 2019 Feb 8;5(1):e000840. doi: 10.1136/rmdopen-2018-000840. eCollection 2019.

Results Reference

derived

PubMed Identifier

30341453

Citation

Bykerk VP, Burmester GR, Combe BG, Furst DE, Huizinga TWJ, Ahmad HA, Emery P. On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis. Rheumatol Int. 2018 Dec;38(12):2225-2231. doi: 10.1007/s00296-018-4173-3. Epub 2018 Oct 20. Erratum In: Rheumatol Int. 2019 Feb 5;:

Results Reference

derived

PubMed Identifier

26865601

Citation

Peterfy C, Burmester GR, Bykerk VP, Combe BG, DiCarlo JC, Furst DE, Huizinga TW, Wong DA, Conaghan PG, Emery P. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1501-5. doi: 10.1136/annrheumdis-2015-208258. Epub 2016 Feb 10.

Results Reference

derived

PubMed Identifier

25367713

Citation

Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E, Karyekar CS, Wong DA, Huizinga TW. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015 Jan;74(1):19-26. doi: 10.1136/annrheumdis-2014-206106. Epub 2014 Nov 3.

Results Reference

derived

Links:

URL

http://www.bms.com/studyconnect/Pages/home.aspx

Description

BMS clinical trial educational resource

Learn more about this trial

Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

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Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial