Safety and Efficacy of Pf-06650833 In Subjects With Rheumatoid Arthritis, With An Inadequate Response To Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: PF-06650833; Placebo; Tofacitinib
Intervention description: Investigational; Placebo; Investigational
Intervention MeSH terms: Tofacitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 269.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and
      active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at
      Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to
      MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting
      conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered
      orally BID for 12 weeks in a blinded fashion.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female (including WOCBP) subjects between the ages of 18 and 75 years,
             inclusive.

          2. Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European
             League Against Rheumatism (EULAR) classification criteria for RA with a Total Score
             ≥6/10.

          3. The subject has active disease at both Screening and Baseline, as defined by both:

               -  6 joints tender or painful on motion, AND

               -  6 joints swollen; and fulfills 1 of the following 2 criteria at Screening:

               -  High sensitivity C reactive protein (hsCRP) >7 mg/L at screening

               -  Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;

          4. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status
             in RA.

          5. Subjects must be ACPA positive between screening and randomization.

          6. Subjects must have been taking oral MTX for at least 3 months at an adequate dose to
             determine that the subject had an inadequate response to MTX

          7. Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting
             biologic agent administered that was inadequately effective and/or not tolerated. The
             anti-TNF biologic could also have been discontinued due to lack of continued access.

        Exclusion Criteria:

          1. Subjects with a known immunodeficiency disorder or a first degree relative with a
             hereditary immunodeficiency.

          2. Subjects with any of the following infections or infections history:

               1. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).

               2. Any infection requiring hospitalization, parenteral antimicrobial therapy within
                  60 days, or as otherwise judged to be an opportunistic infection or clinically
                  significant by the investigator, within the past 6 months.

               3. Infected joint prosthesis at any time with the prosthesis still in situ.

               4. Recurrent (more than one episode) herpes zoster or disseminated (a single
                  episode) herpes zoster or disseminated (a single episode) herpes simplex.

               5. Subjects will be screened for HIV. Subjects who test positive for HIV will be
                  excluded from the study.

               6. Subjects will be screened for hepatitis B virus infection and will be excluded if
                  positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative
                  testing but who test positive for hepatitis B core antibody (HBcAb) must have
                  further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative,
                  the subject will be excluded from the study.

               7. Subjects with clinically significant active hepatic disease or hepatic impairment
                  by laboratory assessment.

               8. Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive
                  HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only
                  subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.

          3. Evidence of active or latent, untreated or inadequately treated infection with
             Mycobacterium tuberculosis (TB)

          4. Pre-existing chronic autoimmune disease.