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:

* Patients with established adult rheumatoid arthritis currently on Methotrexate for at least 3 months

Exclusion Criteria:

* All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
* Previous clinical trials participation and previous biological therapy that could interfere with the results of the present clinical trial
B: Inclusion Criteria:

* Subjects with a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 3 months duration but no longer than 15 years
* Subjects with an active adult Rheumatoid Arthritis disease
* Subjects who have been on Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy for at least 12 weeks

Exclusion Criteria:

* Subject must not have a secondary, non-inflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject's primary diagnosis of Rheumatoid Arthritis (RA)
* Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis)
* Subject must not have a history of an infected joint prosthesis at any time with prosthesis still in situ
* Subject must not have received more than 1 biological agent
* Subject must not have a history of lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time
* Subject with known Tuberculosis (TB) disease, high risk of acquiring TB infection or latent TB infection
* Subject must not have a known hypersensitivity to any components of the investigational medicinal product
* Subject must not have contraindications for Magnetic Resonance Image (MRI) and contrast agent
* Subject must not have any other condition which, in the investigator's judgement, would make them unsuitable for inclusion in the study
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:

1. Patients (more than 18 years) with rheumatoid arthritis according to the ACR classification criteria (1) who have had the diagnose \< 6 months.

2. Moderate to severe rheumatoid arthritis defined as DAS28 (CRP-based) \> 3.2.

3. Negative pregnancy test (serum HCG) for women of childbearing potential prior to trial start. (Non-fertile women are defined as postmenopausal for at least 1 year or surgical sterilisation (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Fertile women included in the trial should use contraception during the entire trial period (i.e. one of the following methods: Oral contraception, intrauterine device (IUD), depot injection of progesterone, subdermal implantation, contraceptive vaginal ring, transdermal depot plaster). In addition, contraception should be used for a period of 150 days after any discontinuation of trial medicine.

4. Ability and willingness to inject the sc. injections him/herself or to have an assistant give the injections.

5. Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion Criteria:

1. Persons with latent TB defined with a positive Mantoux test (\>12 mm for vaccinated and 6 mm for non-vaccinated), positive cultivation of mycobacteria in tissue samples, chest X-ray indicating TB,or other risk factors for activation of untreated latent TB, and persons not been given adequate TB prophylaxis according to the instructions of the department.

2. Active or recurrent infections or severe infections requiring hospitalization or treatment with i.v. antibiotics within the last 30 days or oral antibiotics within the last 14 days prior to inclusion

3. Positive serology for Hepatitis B or C indicating active infection.

4. Medical history with a positive HIV status (Check of HIV test upon suspicion).

5. Medical history with histoplasmosis or listeriosis.

6. Previous cancer or lymph proliferative disease except cases teated radically and have been without relapse for a minimum of 5 years.

Patients with previous squamous cell carcinoma, basal cell skin carcinoma or cervical dysplasia, who have been treated successfully and radically can be included.

7. Previous diagnosis or signs of demyelinized disease in the CNS system (e.g. optic neuritis, visual disorder, disturbed gait, facial paralysis, apraxia).

8. Severe renal insufficiency (creatinine clearance \< 35 ml/min - nomogram).

9. Affected liver function: Liver enzymes \> 2 x above normal limit value.

10. Clinical significant drug or alcohol abuse during the past year and/or current daily alcohol consumption.

11. Unstable diabetes, unstable ischemic heart disease, heart insufficiency (NYHA III-IV), active chronic inflammatory intestinal disease, recent cerebral apoplexia (within 3 months), chronic leg ulcer or any other condition (e.g. kateter a demeure)which according to the investigator imposes an increased risk to the subject, if he/she participates in the protocol.

12. Anticoagulant therapy.

13. Pregnancy or breast-feeding.

14. Other inflammatory rheumatic diseases.

15. Aggressive parvovirus B19 infection.

16. Previous treatment with one or more DMARDs.

17. Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids).

18. Contraindications for trial medicine.

Answer: C