Rheumatoid Arthrithis, Nos
Conditions
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * Subject is willing to participate in the study and signed the informed consent. * Subjects must meet the criteria of the American Rheumatism Association (1987) for the diagnosis of rheumatoid arthritis and the American College of Rheumatology (1991) functional Classes I, II, or III. (Refer to protocol appendices 1 and 2.) * Subjects must have been taking methotrexate for at least 3 months at a weekly dose of at least 15 mg, and at a stable dose for 28 days prior to treatment (Day 1) * Men and women, ages 18 = 75 years old. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures. * Methotrexate alone: Subjects who are treated only with methotrexate will not require washout. * Methotrexate plus other DMARDs: Subjects who are treated with methotrexate in combination with another anti-rheumatic treatment (DMARD) will require washout of the other DMARD. * Drug stabilization requirements (except methotrexate) a) All DMARDs (except methotrexate) should be discontinued at least 28 days prior to treatment (Day 1). i) In the case of leflunomide, the subject can be washed out with cholestyramine according to manufacturer recommendations. b) Oral corticosteroid treatment must have been reduced to the equivalent of 10 mg prednisone daily for 28 days and stabilized for at least 25 out of 28 days prior to treatment (Day 1). For Subjects Receiving Methotrexate Alone: At randomization (Day 1), subjects must have the following disease activity: a) 10 or more swollen joints (66 joint count) and b) 12 or more tender joints (68 joint count) and c) C-reactive protein (CRP) = 1 mg/dL (Result used from screening visit) For Subjects Receiving Other DMARDs Plus Methotrexate: At screening visit, subjects must have the following disease activity: a) 6 or more swollen joints (66 joint count) and b) 8 or more tender joints (68 joint count) and c) No restriction on CRP IN ADDITION All subjects who are receiving other DMARDs plus methotrexate therapy at the screening visit must undergo a 28 day washout period of their other anti-rheumatic treatment (DMARD) (other than methotrexate). After washout at randomization (Day 1), subjects must have the following disease activity: a) 10 or more swollen joints (66 joint count) and b) 12 or more tender joints (68 joint count) and c) C reactive protein (CRP) = 1 mg/dL. (Result used from Day -3 visit). Long-Term Extension (Protocol Amendment 03) Subjects must be willing to participate in the long term extension and sign consent. Subjects who enter the long term extension must continue to meet Inclusion/ Exclusion criteria as outlined in Protocol IM101043 and/or all subsequent amendments, with the exception of tender and swollen joint counts, CRP, dose of methotrexate, PPD skin testing, and male contraception use requirement. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last infusion of abatacept * Any previous or current medical conditions that are contraindications to the use of TNF blocking agents. (Please refer to Appendix 11 and 12 Remicade Labels) * Subjects who have previously received treatment with an approved biologic RA therapy (Infliximab, Etanercept, Anakinra, Adalimumab). * Subjects who have failed more than 4 DMARDs (including methotrexate) due to lack of efficacy (DMARDs approved for the treatment of RA include methotrexate,hydroxycholoroquine, sulfasalzine, leflunomide, azathioprine, and gold). * Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules). * Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease. * Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations * Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. * Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years. Subjects with a positive PPD at screening will not be eligible for the study unless active TB infection has been ruled out, they have initiated treatment for latent TB for at least 4 weeks prior to dosing of study drug, and they have a negative chest x-ray at enrollment. * Hepatitis B surface antigen-positive subjects. * Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive. * Subjects with any of the following laboratory values: • Hgb 2 times upper limit of normal. • Serum ALT or AST > 2 times upper limit of normal.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that the abatacept in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months (Day 197). Long-Term extension (amendment 03) To assess the safety and long-term tolerability of abatacept in subjects who have completed the initial 12-month double-blind treatment period. Secondary objectives will be to assess efficacy and immunogenicity of abatacept in combination with background DMARDs during this long-term extension phase (see protocol amendment 03 - section 2.2). Long-Term extension (amendment 05) to assess the safety and long-term tolerability of abatacept in subjects who will continue in the long-term extension. Secondary objectives will be to assess the immunogenicity of abatacept in combination with methotrexate.;Secondary Objective: * To demonstrate that infliximab in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months. * Compare the reduction in disease activity over time as measured by the DAS28 area under the curve (DAS28AUC) over 12 months in subjects receiving abatacept versus infliximab in combination with methotrexate. * Assess the change in physical function and the subject’s health-related quality of life as measured by the disability index of the HAQ and the SF-36 questionnaire respectively, in subjects receiving placebo, abatacept, or infliximab in combination with methotrexate at 6 months and 12 months * Determine the proportion of subjects treated with abatacept or infliximab at 12 months who demonstrate a good, moderate or no response according to the EULAR response criteria. (see protocol for additional secondary objectives).;Primary end point(s): The primary end point will be the comparison of abatacept versus placebo for changes f | — |
Countries
Czech Republic, Denmark, Spain, Sweden
Outcome results
None listed