Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Exploratory Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess The Pharmacodynamics Of CP-690,550, Administered Orally Twice Daily (BID) For 4 Weeks, In Subjects With Active Rheumatoid Arthritis
Brief Summary: To explore the effect of CP-690,550 on blood and synovial markers in subjects with rheumatoid arthritis. To evaluate the safety, tolerability and efficacy of CP-690,550.


Options:
A: Inclusion Criteria:

* adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
* inadequate response to a stable dose of MTX;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
* prior treatment failure with an anti-tumor necrosis factor agent;
* women who are pregnant or breast-feeding.
B: Inclusion Criteria:

* Diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al, 1988). The disease should have been diagnosed at least 6 months prior to screening.
* Active disease at the time of screening and pre-infusion as defined by:

  * \>=6 swollen joints
  * \>=6 tender joints and 2 of the following:

    * morning stiffness \>=45 min
    * ESR \>=28 mm/h
    * CRP \>=20 mg/L
* Men and women, \>=18 to \<=75 years of age
* Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, IUD, barrier method with spermicide or, surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion.
* Patients must have been using oral or parenteral MTX for at least 3 months with no break(s) in treatment of more than 2 weeks total during this period. Patients must have been on a stable dose of \>=12.5 mg/wk (maximum 20mg/wk) for at least 4 weeks prior to screening.
* Patients must be on a stable dose of folic acid prophylaxis for at least 4 weeks prior to screening.
* Patients using oral corticosteroids, must have been on a stable dose of \<=10 mg/day for at least 4 weeks prior to screening. If currently not using corticosteroids the patient must have not received corticosteroids for at least 4 weeks prior to screening.
* If using NSAIDs, patients should have been on a stable dose for at least 4 weeks prior to screening. If currently not using NSAIDs the patient must have been off for at least 4 weeks prior to screening.
* The screening laboratory tests must meet the following criteria:

  * Hemoglobin \>=5.3 mmol/L (\>=8.5 g/dL), providing a low hemoglobin level is not due to nutritional deficiencies or due to diseases other than chronic RA
  * WBC \>=3.5 x 10\^9/L
  * Neutrophils \>=1.5 x 10\^9/L
  * Platelets \>=100 x 10\^9/L
  * Serum transaminase \<=2 times the upper limit of normal
  * Alkaline phosphatase levels \<=2 times the upper limit of normal
  * Serum creatinine \<=150 µmol/L (\<=1.7 mg/dL)
* Patient must be able to adhere to the study visit schedule and other protocol requirements.
* Patient must be capable of giving informed consent and the consent must have been obtained prior to any study procedures including wash-out period.

Exclusion Criteria:

* Pregnant women, nursing mothers or a planned pregnancy within 1.5 years of enrollment.
* Patients who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.
* Patients who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from the Infliximab therapy, eg Lyme disease, or a rheumatic disease other than RA.
* Use of DMARDs other than MTX within 4 weeks prior to screening. (If a patient had prior exposure to leflunomide within the past 6 months, cholestyramine 8 g should be given 3 times daily for 11 days to rapidly lower the plasma level of leflunomide.)
* Use of intra-articular, i.m. or i.v. corticosteroids (including i.m. ACTH) within 4 weeks prior to screening.
* Have been previously treated with infliximab or genetic recombinant therapy with RA (e.g. etanercept, adalimumab).
* Treatment with any other therapeutic agent targeted at reducing TNF (eg, pentoxifylline or thalidomide) within the previous 3 months.
* Treatment with any investigational drug within the previous 3 months.
* Prior use of cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
* Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.
* History of infected joint prosthesis within previous 5 years.
* Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months.
* Chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis.
* Have active TB. Also excluded are patients who have evidence of latent TB (positive PPD skin test or a history of latent TB) without adequate therapy for TB initiated prior to first infusion of study drug. Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy, if they will not be treated with antitubercular therapy during the trial. Patients with a current close contact with an individual with active TB will also be excluded. Additionally, patients who have completed treatment for active TB within the previous 2 years are now explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrollment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies. Also excluded are patients with opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, or atypical mycobacterial infection, etc, within the previous 6 months.
* Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
* History of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or splenomegaly.
* Any current known malignancy or history of malignancy within the previous 5 years, except for squamous or basal cell carcinoma of the skin that have been treated with no evidence of recurrence.
* Patients with moderate or severe heart failure (NYHA class III/IV)
* Patients with pre-existing or recent onset of central nervous system demyelinating disorders
* Known recent substance abuse (drug or alcohol).
* Patients in whom multiple venipunctures are not feasible due to poor tolerability or lack of easy access.
* Have a known infection with HIV or known active hepatitis B/C infection (including associated chronic active hepatitis).
C: Inclusion Criteria:

* Subject must have a diagnosis of rheumatoid arthritis based on the American College of Rheumatology Association
* The subject has active disease at both Screening and Baseline, as defined:

  * ≥4 joints tender or painful on motion, AND
  * ≥4 joints swollen;
* The subject must have at least one knee, one elbow, one wrist or two metacarpophalangeal joints with active synovitis suitable for biopsy by the shaver technique

Exclusion Criteria:

* No arthroscopy should have been performed in the past 3 months in the same joint that is to be biopsied in this study.
* No intra-articular steroids should have been injected in the joint to be biopsied in this study in the previous 3 months.
* Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels \< 9.0 gm/dL or hematocrit \< 30 % at screening visit or within the 3 months prior to baseline synovial biopsy.
* An absolute white blood cell (WBC) count of \< 3.0 x 109/L (\<3000/mm3) or absolute neutrophil count of \<1.2 X 109/L (\<1200/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
* Thrombocytopenia, as defined by a platelet count \<100 x 109/L (\< 100,000/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
* Estimated GFR less than 40 ml/min based on Cockcroft Gault calculation .
D: Inclusion Criteria:

* The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
* The patient must have had an inadequate response to methotrexate and have active disease, 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: 1.ESR (Westergren method) \>28 mm in the local laboratory. 2. CRP \>7 mg/L in the central laboratory.
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
* The patient must have been on a stable dose of 7.5 mg to 25 mg weekly of methotrexate and washed out of all other DMARDs.

Exclusion Criteria:

* Blood dyscrasias including confirmed: 1. Hemoglobin \<9 g/dL or Hematocrit \<30%; 2. White blood cell count \<3,000 cu.mm. Absolute neutrophil count \<1,200 cu.mm; 4. Platelet count \<100,000/L
* History of any other autoimmune rheumatic disease other than Sjogren's syndrome
* No malignancy or history of malignancy.
* History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug
* Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event.
* Patients who have previously received adalimumab therapy for any reason.
* Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label.
* Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure

Answer: C