Abatacept With Methotrexate- Phase IIB
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Abatacept (BMS-188667); Abatacept (BMS-188667); Abatacept (BMS-188667); Placebo
Intervention description: IV, 10 mg/Kg, monthly, for the duration of the trial; Intravenous (IV) infusion, 2 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months; Intravenous (IV) infusion, 10 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months; Intravenous (IV) infusion, 0 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 524.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study was conducted to assess the safety and tolerability of Abatacept combined with
      Methotrexate in participants with active rheumatoid arthritis (RA). The secondary objectives
      were to assess efficacy, pharmacodynamic marker activity, and immunogenicity of Abatacept
      combined with Methotrexate.
    

Eligibility criteria:

        Inclusion Criteria:

        Double blind study phase:

          1. Males or females (not nursing and not pregnant), at least 18 years of age. Women of
             child bearing potential (WOCBP) are eligible if they are practicing effective
             contraceptive measures

          2. 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

          3. Subjects have been taking Methotrexate (10-30 mg weekly) for at least 6 months, and at
             a stable dose for 28 days prior to treatment

          4. Washout/drug stabilization requirements (except Methotrexate) [Informed consent must
             be signed before making any changes in RA therapy if those changes are solely for the
             purpose of this study].

               -  Leflunomide or Infliximab have already been discontinued at least 60 days prior
                  to enrollment (prior to signing of informed consent) and a total of 90 days prior
                  to treatment. All other Disease Modifying Anti-Rheumatic Drugs (DMARDs) (except
                  Methotrexate) have been withdrawn at least 28 days prior to treatment

               -  Oral corticosteroid treatment has been reduced to the equivalent of 10 mg or less
                  prednisone daily and stabilized for at least 28 days prior to enrollment

          5. Eligibility of subjects for the study is based on their disease activity and
             anti-rheumatic treatment at the initial visit:

               -  Methotrexate monotherapy: Subject is receiving only Methotrexate, steroids,
                  Non-steroidal anti-inflammatory drugs (NSAIDs) and will not require washout

               -  Combination therapy: Subject is receiving Methotrexate in combination with
                  another DMARD(s) and will require washout

             At entry, Methotrexate monotherapy must have a disease activity:

               -  10 or more swollen joints (66 joint count)

               -  12 or more tender joints (68 joint count)

               -  C reactive protein (CRP) ≥.1 mg/dL (10 mg/L) at "Screening" visit

             At entry, combination therapy must have a disease activity (if subject does not
             satisfy the above):

               -  6 or more swollen joints (66 joint count)

               -  8 or more tender joints (68 joint count)

               -  No restriction on C-reactive protein (CRP)

             In addition

             All subjects who were on combination therapy at entry must undergo a 28 day washout
             period of DMARDs other than Methotrexate. After the washout/drug stabilization and
             prior to randomization such subjects must have:

               -  10 or more swollen joints (66 joint count)

               -  12 or more tender joints (68 joint count)

               -  C reactive protein (CRP) ≥ 1 mg/dL (10 mg/L)

          6. Subject is willing to participate in the study and willing to sign the informed
             consent

        Open label study phase:

          -  Participants that have completed the initial short term portion (double blind) of the
             study

        Exclusion Criteria:

        Double blind study phase:

          1. Subjects who have at any time received treatment with BMS-188667 (Abatacept)

          2. Subjects who within 30 days of the Day 1 visit have received treatment with any
             investigational drug

          3. Subjects with active vasculitis of a major organ system (except for subcutaneous
             rheumatoid nodules)

          4. Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
             hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral
             disease. Concomitant medical conditions that in the opinion of the investigator might
             place the subject at unacceptable risk for participation in this study

          5. Mammogram requiring further investigation or biopsies leading to the diagnosis of a
             clinically significant abnormality. Complete evaluation of lesion is required before
             initiation of dosing

          6. Subjects with a history of cancer within the last five years (other than non-melanoma
             skin cell cancers cured by local resection)

          7. Subjects who have a history of clinically significant drug or alcohol abuse, or admit
             to consumption of more than 1 alcoholic drink per day

          8. Subjects with evidence (as assessed by the investigator) of active or latent bacterial
             or viral infections at the time of potential enrollment, including subjects with
             evidence of Human Immunodeficiency Virus (HIV) infection, or hepatitis B or C
             infection

          9. Subjects with any serious or chronic infections such as pneumonia, pyelo-nephritis,
             renal infection, chest infection with bronchiectasis, or sinusitis in the previous 3
             months

         10. Subjects with active tuberculosis requiring treatment within the previous 3 years

         11. Subjects with any opportunistic infections such as herpes zoster or cytomegalovirus
             (CMV) within the previous 2 months

         12. Subjects with severe asthma defined as > 3 emergency room admissions in the last year
             or > 3 treatments with oral steroids for asthma in the last year

         13. A history of either angioedema or anaphylaxis that was associated with a reaction to a
             drug

         14. Subjects with the following laboratory values:

               -  Hemoglobin < 8.5 g/dL

               -  White blood cells < 3000/mm3

               -  Platelets < 100,000/mm3

               -  Serum creatinine > 2 times upper limit of normal

               -  Serum Alanine aminotransferase (ALAT) or Aspartate aminotransferase (ASAT) > 2
                  times upper limit of normal

               -  Any other lab values that in the opinion of the investigator might place the
                  subject at unacceptable risk for participation in this study

        Open label study phase:

          -  Participants must continue to meet inclusion/exclusion criteria as in the short term
             (double blind) phase of the protocol except subjects who have receiving other than
             Abatacept