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Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00124449
First received: June 30, 2005
Last updated: July 28, 2010
Last verified: November 2009
  Purpose

The purpose of this study is to assess if Abatacept given for six months will prevent rheumatoid arthritis (RA) in patients who are at risk for the development of RA in comparison to placebo. High risk patients are defined as those having a positive laboratory test for anti-cyclic citrullinated peptide (anti-CCP2).


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Abatacept
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Phase II Study of Abatacept Versus Placebo to Assess the Prevention of Rheumatoid Arthritis (RA) in Adult Patients With Undifferentiated Arthritis Who Are at High Risk for the Development of RA

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With a Diagnosis of Rheumatoid Arthritis (RA) by American Rheumatism Association (ARA) Criteria and/or Discontinued Due to Lack of Efficacy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    ARA criteria is a 7-item tool for RA classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting primary endpoint also.


Secondary Outcome Measures:
  • Number of Participants With a Diagnosis of RA by 1987 ARA Criteria and/or Discontinued Due to Lack of Efficacy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    ARA criteria is a 7-item tool for classification purposes; a patient is said to have RA (meeting endpoint) if he or she has satisfied at least 4 of the 7 criteria. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.

  • Number of Participants With Undifferentiated Inflammatory Arthritis (UA) Who Develop Another Rheumatic Disease [ Time Frame: 12 months, 24 months ] [ Designated as safety issue: No ]
    Clinical diagnosis of other rheumatic diseases at 12 and 24 months. If a participant discontinued due to lack of efficacy, he/she was regarded as meeting endpoint also.

  • Change From Baseline in Radiographic Erosion and Joint Space Narrowing Score at 6 Months, 12 Months, and 24 Months [ Time Frame: Baseline, 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    Mean change from baseline using the Genant-Modified Sharp Score. Erosion score=assessment of 14 sites in each hand and wrist + 6 joints in each foot, using an 8-point scale from 0 (no erosions) to 3.5 (erosions of 100% or articular surfaces). Joint score= assessment of 13 sites in each wrist and hand + 6 sites in each foot using a 9-point scale from 0 (normal) to 4.0 (definite ankylosis). As-observed data. Change from Baseline=postbaseline score at timepoint (6 or 12 or 24 months) minus baseline score; a lower value signifies improvement.

  • Change From Baseline in Total Erosion, Edema, Synovitis Scores at 6 Months, 12 Months, and 24 Months [ Time Frame: Baseline, 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    Mean change from baseline. Degree of synovitis and structural joint damage (erosion, edema) of the carpal and metacarpophalangeal joints, as measured by magnetic resonance imaging (MRI) scores using the European League Against Rheumatism (EULAR)-Outcome Measures in Rheumatology Clinical Trials (OMERACT) assessment. Edema scale=0 (no bone involved) to 3 (67% to 100% of bone involved). Synovitis scale=0 (normal) and 1-3 (mild, moderate, severe. Bone erosion scale=0 (0% of bone involved) to 10 (91% to 100% of bone involved). Change from baseline=postbaseline score at timepoint - baseline score.

  • Number of Participants With Persistent Symptomatic Clinical Synovitis [ Time Frame: 6, 12, and 24 months ] [ Designated as safety issue: No ]
    Synovitis, assessed by clinical signs and symptoms

  • Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) Scores - Mean Change From Baseline [ Time Frame: 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    SF-36, a 36-item instrument that covers 8 quality of life domains, which were used to derive the physical and mental component summary scores, which ranged from 0 to 100, with higher scores indicating a better quality of life. Change from baseline=postbaseline - baseline value; a higher value signifies improvement.

  • Change From Baseline in Cytokine Levels and Second Generation Anti-cyclic Citrullinated Peptide (Anti-CCP2) Antibodies at 6 Months, 12 Months, and 24 Months [ Time Frame: Baseline, 6 Months, 12 months, 24 months ] [ Designated as safety issue: No ]
    To assess pharmacodynamic effect of abatacept on serum levels of autoantibodies, mean change from baseline in cytokines (interleukin-6 [IL-6], interleukin-1B [IL-1B], tumor necrosis factor Alpha [TNF-Alpha], Matrix Metalloproteinase 3T [MMP3T], and anti-CCP2), as measured by standard laboratory investigations, were assessed. Change from baseline=postbaseline value at timepoint (6 or 12 or 24 months) minus baseline value; a lower value signifies improvement.

  • Number of Participants With Anti-CCP2 Positive and/or Rheumatoid Factor (RF) Positive Over Time [ Time Frame: Day 1, 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, number of participants with Anti-CCP2 Positive of Rheumatoid Factor (RF) positive

  • Frequency of Human Leukocyte Antigen (HLA) Typing [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    To assess the pharmacodynamic effect of abatacept on serum levels of autoantibodies, a blood sample was obtained for HLA typing to determine the presence or absence of alleles associated with RA susceptibility and severity (shared epitope alleles HLA-DRB10401 and HLA-DRB10404).

  • DAS 28 C Reactive Protein (CRP) Score - Mean Change From Baseline [ Time Frame: 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    The DAS 28 (CRP) is a composite of 4 variables: 28 tender joint count, 28 swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Change from Baseline=postbaseline score-baseline score; a lower value signifies improvement.

  • Number of Participants With a DAS 28 (CRP) Score of ≤3.2 (Low Disease Activity) or <2.6 (in Remission) [ Time Frame: 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    The DAS 28 (CRP) is a composite of 4 variables: tender joint count, swollen joint count, CRP, and subject assessment of disease activity measure on a VAS of 100 mm. Scores for disease activity are defined as low (≤ 3.2) and in remission (< 2.6).

  • Number of Subjects With Health Assessment Questionnaire (HAQ) Disability Index Response [ Time Frame: 6 months, 12 months, 24 months ] [ Designated as safety issue: No ]
    This questionnaire includes 20 questions assessing physical function in 8 domains. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. Higher scores indicate greater dysfunction. HAQ response =improvement of at least 0.3 units from baseline.

  • Overall Safety - Adverse Events (AEs), Serious AEs, and Deaths [ Time Frame: Throughout the treatment period (6 months) ] [ Designated as safety issue: Yes ]
    AEs were monitored at all scheduled visits of the study drug treatment and observation periods and at the follow-up visits performed 28, 56, and 85 days after the last infusion of study medication for participants who were withdrawn prematurely

  • Number of Participants With Positive Responses for Serum Levels of Abatacept-specific Antibodies [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Immunogenicity, as measured by the number of positive repsonses for serum levels of abatacept-specific antibodies measured by enzyme-linked immunosorbent assays (ELISA). Postive response for whole molecule assessment was a value of > 400 and for tip assessment was ≥25.


Enrollment: 56
Study Start Date: February 2005
Study Completion Date: April 2008
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Abatacept

solution, intravenous injection, monthly, 169 days

weight based:

<60 kg = 500 mg

60 to 100 kg = 750 mg

>100 kg = 1 g

Other Name: Orencia
Placebo Comparator: 2 Drug: placebo
solution, intravenous injection, 0 mg, monthly, 169 days

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of undifferentiated arthritis
  • Clinical synovitis of two or more joints
  • At least one but not more than three of the criteria for diagnosis of RA (1987).
  • No prior disease modifying anti-rheumatic drugs (DMARDs)/biologics.
  • Duration of disease must be 18 months or less.
  • Positive for antibodies against cyclic citrullinated peptides.

Exclusion Criteria:

  • Women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy.
  • Active vasculitis of a major organ system.
  • Severe or recurrent bacterial infection.
  • History of cancer in the last five years except certain skin cancers.
  • Herpes zoster that resolved less than 2 months prior to enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124449

  Show 48 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00124449     History of Changes
Other Study ID Numbers: IM101-046
Study First Received: June 30, 2005
Results First Received: May 21, 2009
Last Updated: July 28, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Abatacept
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014