Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Fostamatinib disodium (R935788); Placebo
Intervention description: R935788 100 mg tablet, orally, twice-a-day; Placebo, orally, twice-a-day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 219.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) Inhibitor,
      R935788 (R788) at a dose of 100 mg, tablet, orally, twice-a-day is effective in the treatment
      of Rheumatoid Arthritis in patients who have 'failed' a biologic therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must give written informed consent by signing an IRB/EC-approved Informed
             Consent Form (ICF) prior to admission to this study.

          -  Males and females, 18 years of age or older, with active RA for at least 12 months
             prior to Day 1 dosing

          -  Are currently receiving or previously had received a biologic therapy with an
             inhibitor of TNF, rituximab, abatacept, or anakinra at an approved labeled dose for ≥3
             months prior to Day 1 dosing and are designated as biologic therapy failures for lack
             of efficacy, safety, or tolerability.

          -  Patients may receive stable doses of methotrexate (MTX), azathioprine (not in
             combination with MTX), leflunomide (not in combination with MTX), sulfasalazine,
             chloroquine, hydroxychloroquine, gold, NSAIDs (including COX2 inhibitors),
             minocycline, or doxycycline. The dose must have been stable for at least 30 days prior
             to Day 1 dosing and must not be changed during the washout, screening and treatment
             periods, unless dictated by tolerability requirements. Patients who are taking MTX
             must have been receiving weekly MTX doses (7.5-25 mg/week) for a minimum of 3 months
             prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in
             route, for the previous 6 weeks prior to Day 1 dosing. Patients who are receiving MTX
             must also be receiving folic or folinic acid supplementation at a stable dose for at
             least 6 weeks prior to Day 1 dosing.

          -  Females of childbearing potential must be fully informed of the potential for R788 to
             adversely affect the fetus and, if sexually active, must agree to use a well
             established method of birth control during the study (oral contraceptive, mechanical
             barrier, long acting hormonal agent). These patients must not be lactating and must
             have a negative urine pregnancy test at the time of randomization and at each
             laboratory determination.

          -  The patient must otherwise be in good health as determined by the Investigator on the
             basis of medical history, physical examination, and laboratory screening tests during
             the screening period. See exclusion criteria for specific exclusions.

          -  In the Investigator's opinion, the patient has the ability to understand the nature of
             the study and any hazards of participation, and to communicate satisfactorily with the
             Investigator and to participate in, and to comply with, the requirements of the entire
             protocol.

        Exclusion Criteria:

          -  The patient has a history of, or a concurrent, clinically significant illness, medical
             condition (other than arthritis) or laboratory abnormality that, in the Investigator's
             opinion, could affect the conduct of the study. Specifically, excluded are patients
             with the following:

               1. uncontrolled or poorly controlled hypertension;

               2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder)
                  or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);

               3. recent serious surgery or infectious disease;

               4. recent history ( of, or treatment for, a malignancy other than nonmelanomatous
                  skin cancer, or any history of lymphoma;

               5. Hepatitis B;

               6. Hepatitis C;

               7. interstitial pneumonitis or active pulmonary infection on chest x-ray

               8. Tuberculosis (TB)

               9. known laboratory abnormalities

          -  The patient has a history of substance abuse, drug addiction or alcoholism. Patients
             may consume up to 4 units of alcohol per week; however, alcohol should be avoided in
             the 72 hours prior to lab assessments. Patients who cannot reliably comply with this
             should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355
             mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled
             spirits= 1.5 oz or 44 mL.

          -  The patient has been treated previously treated with R788 under a different protocol.

          -  The patient has a pacemaker, aneurysm clip or other contraindication to MRI.