Clinical trial NCT00254293: Study to Assess Steady-State Trough Concentrations, Safety, and Immunogenicity of Abatacept After Subcutaneous (SC) Administration to Subjects With Rheumatoid Arthritis (RA)
Official title: A Study to Assess the Steady-State Trough Serum Concentration, Safety, and Immunogenicity of Abatacept (BMS-188667) Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Who Are Receiving Disease Modifying Ant-Rheumatic Drugs (DMARDs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-11-16
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to study serum levels of Abatacept after subcutaneous dosing in subjects with RA.


Eligibility criteria: Inclusion Criteria:

* Meet ARA criteria for diagnosis of RA with active disease.
* RA diagnosis for at least 1 year.
* \> = 6 swollen joints.
* \> = 8 tender joints.
* Taking methotrexate (MTX) or MTX plus not more than 1 added oral DMARD for \> = 3 months and stable for 28 days prior to dosing.

Exclusion Criteria:

* Serious acute or bacterial infection in last 3 months.
* Chronic or recurrent bacterial infections.
* History of TB within previous 3 years or old TB not adequately treated.
* Specific lab test abnormalities
* History of cancer within 5 years.
* Exposure to CTLA4Ig (Cytotoxic T-lymphocyte (T-cell)-associated antigen 4Ig), belatacept, rituximab, efalizumab, alefacept, or other investigational drug or biologic.
* Treatment with hydroxychloroquine, azathioprine, leflunomide, immunoadsorption columns, mycophenolate mofetil, cyclosporine, D-Penicillamine or calcineurin inhibitors.
* Exposure to live vaccines.

Primary outcomes:
measure: Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS)
timeFrame: Days 71 to 85
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE)
timeFrame: Day 85 to 56 days post last dose
measure: Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE)
timeFrame: Day 85 to Day 533
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing)
timeFrame: Day 533 to 56 Days Post last dose
Secondary outcomes:
measure: Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Day 71 to Day 78
measure: Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Day 71 to Day 78
measure: Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85)
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Day 1 to Day 85 (or early termination)
measure: Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Screening to Day 85 (or early termination)
measure: Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS
timeFrame: Screening to Day 85 (or early termination)
measure: Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies
timeFrame: ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: New Orleans
country: United States
facility: New Orleans Center For Clinical Research
state: Louisiana
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
city: Charlotte
country: United States
facility: The Arthritis Clinic & Carolina Bone & Joint
state: North Carolina
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Westhovens R, Kremer JM, Moreland LW, Emery P, Russell AS, Li T, Aranda R, Becker JC, Qi K, Dougados M. Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study. J Rheumatol. 2009 Apr;36(4):736-42. doi: 10.3899/jrheum.080813. Epub 2009 Feb 27.