Methotrexate Withdrawal Study of Tofacitinib Modified Release Formulation in Subjects With Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: CP-690,550; Methotrexate; Placebo
Intervention description: During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose.
During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.; During the open-label run-in phase (Day 1 to Week 24), all subjects will receive one tablet open-label tofacitinib MR 11mg orally QD and open-label methotrexate capsule(s) orally every week at prior stabilized dose.
During the double-blind phase, subjects who are randomized to the treatment arm will receive the same dosage of tofacitinib and methotrexate as describe above.; During the double-blind phase, subjects who are randomized to the comparison arm will receive 11mg QD tofacitinib and the placebo capsules matching for methotrexate.
Intervention MeSH terms: Methotrexate; Tofacitinib
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 694.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; Tofacitinib; CP-690,550; Xeljanz; methotrexate withdrawal; withdrawal study

Summary:

      This study is designed to evaluate the efficacy and safety of tofacitinib modified release
      formulation (11mg QD) versus tofacitinib modified release formulation plus continued
      methotrexate treatment in subjects with moderate to severe rheumatoid arthritis who are
      insufficiently responding to their stable dose of methotrexate treatment.
    

Eligibility criteria:

        Key Inclusion Criteria

        - Must be 18 years of age or older.

        Have a score of 6 or greater on the 2010 American College of Rheumatology/European League
        Against Rheumatism Classification Criteria for Rheumatoid Arthritis at and/or prior to
        Screening Visit.

          -  Have ≥4 tender/painful joints on motion and ≥4 swollen joints (28 joint counts) at
             both Screening Visit and Baseline Visit (Visit 1).

          -  Have moderate to severe disease activity as defined by CDAI>10 and DAS28-4(ESR) ≥3.2
             at Baseline Visit.

          -  Have taken an oral MTX treatment regimen (15-25mg/week) continuously for at least 4
             months prior to the screening visit and has taken a stable weekly dose of oral MTX
             with supplemental folic acid or folinic acid for at least 4 weeks prior to the
             baseline visit (conversion from parenteral MTX to oral MTX will require stabilization
             of the treatment regimen for at least 1 month).

          -  Subjects must screen negative for active tuberculosis or inadequately treated
             tuberculosis infection (active or latent).

        Key Exclusion Criteria

          -  Pregnant female subjects; breastfeeding female subjects; male subjects with partners
             currently pregnant; male subjects able to father children and female subjects of
             childbearing potential who are unwilling or unable to use 2 highly effective methods
             of contraception as outlined in this protocol for the duration of the study and for at
             least 3 months after the last dose of investigational product.

          -  Subjects with infection or infection history; subjects with any current malignancy or
             a history of malignancy (except adequately treated or excised non-metastatic basal
             cell or squamous cell cancer of the skin or cervical carcinoma in situ); subjects with
             history of, or current evidence for, severe gastrointestinal narrowing (pathologic or
             iatrogenic); and subjects with history of documented diverticulitis.

          -  Subjects with a history of insufficient response to ≥2 biologics, regardless of the
             class.