A PHASE 2B, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, MULTICENTER STUDY TO COMPARE 6 DOSE REGIMENS OF CP 690,550 VS. PLACEBO, EACH COMBINED WITH METHOTREXATE, ADMINISTERED FOR 6 MONTHS IN THE TREATMENT OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE ALONE. - N/A

• Conditions: Rheumatoid arthritis; MedDRA version: 8.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2006-005036-24-CZ
• Lead Sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-04
• Last Update Posted: 7 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 483

Inclusion Criteria

1.Evidence of a signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.

2.Subjects must be at least 18 years of age.

3.The subject is a sexually active woman of childbearing potential, she and any male partner are required to simultaneously use 2 effective contraceptive methods, from the list of effective contraceptives found in Section 4.4 of this protocol.

4.Non vasectomized men must be willing to abstain from sexual intercourse or willing to use a condom in addition to having their female partner use another form of contraception such as an IUD, barrier method with spermicide, oral contraceptive, injectable progesterone, sub dermal implant, or a tubal ligation, if the woman could become pregnant from the time of the first dose of study medication until completion of follow up procedures.

5.The subject has a diagnosis of RA based upon the American College of Rheumatology 1987 Revised Criteria ,ie, fulfilling at least 4 of the following 7 criteria for at least 6 consecutive months preceding randomization:

a.morning stiffness in and around any joint for more than 1 hour;
b.soft tissue swelling of 3 or more joint areas;
c.swelling of the proximal interphalangeal, metacarpophalangeal (MCP) or wrist joints;
d.symmetrical joint swelling;
e.rheumatoid nodules;
f.serum rheumatoid factor positive;
g.radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.

6.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:

•Erythrocyte sedimentation rate above the upper limit of normal in the local laboratory;
•C reactive protein (CRP) >7 mg/L in the central laboratory.

7.The subject meets ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II or III Appendix A.

8.Subjects must have been taking oral or parenteral methotrexate continuously for at least 4 months, and on a stable dosage of 7.5 to 25 mg weekly for at least 6 weeks prior to first dose of study drug. Stable weekly doses less than 15 mg are allowed only in the presence of documented intolerance to or toxicity from higher doses. Subjects must have an inadequate clinical response to MTX, defined, for the purpose of this study, by the Investigator’s and subject’s opinions that the subject did not experience adequate benefit from methotrexate plus the presence of sufficient residual disease activity to meet the entry criteria.

9.Folic acid must be dosed per local standards of care stably for at least 4 weeks before first study dose.

10.Subjects receiving non prohibited concomitant medications for any reason must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half lives (whichever is longer) prior to first study dose.

11.Subjects having received the following treatment regimens are eligible, providing the following discontinuation periods are observed. Note that none of these therapies should be discontinued by a subject to allow participation in this study if they are currently effective and tolerated.

a. Within 4 weeks of first dose of study drug:
•Biologics anakinra (Kineret®), etanercept (Enbrel®);

Exclusion Criteria

1.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 first study dose.
2.An absolute white blood cell (WBC) count of < 3.0E9/L or absolute neutrophil count of <1.2E9/L at screening visit or within the 3 months prior to first study dose.
3.Thrombocytopenia, as defined by a platelet count <100E9/L at screening visit or within the 3 months prior to first study dose.
4.Estimated GFR =50 ml/min based on Cockcroft Gault calculation.
5. Pregnant or lactating women.
6.Total bilirubin, AST or ALT more than 1.5 times the upper limit of normal at screening visit.
7.Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
8.History of an infected joint prosthesis at any time, with the prosthesis still in situ.
9.Current routine household contact with individuals who have received varicella or FluMist® vaccine within 4 weeks or oral polio vaccine within 8 weeks prior to first study dose, during the 24 weeks of treatment and for 8 weeks following completion of the study.
10.History of any lymphoproliferative disorder, history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease.
11.History of previously untreated infection with Mycobacterium tuberculosis or current treatment for same.
12.Subjects with clinically significant infections currently or within 6 months of first dose of study drug, or those with a history of more than one episode of herpes simplex or zoster, a history of disseminated zoster, a history of any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the trial or any infection requiring antimicrobial therapy within 2 weeks of screening.
13.Failure of prior treatment with 3 TNF inhibitors: etanercept, infliximab and adalimumab.
14.Any prior treatment with lymphocyte depleting agents/therapies. Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least one year prior to study baseline and have normal CD19/20+ counts by FACS analysis.
15.Subjects with any condition possibly affecting oral drug absorption, gastrectomy, or clinically significant diabetic gastroenteropathy.
16.History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug.
17.Screening 12 lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results.
18.Donation of blood in excess of 500 mL within 2 months prior to first study dose.
19.Subjects with an oral or tympanic temperature at Baseline visit of 38°C or higher at screening.
20.Subjects with a first degree relative with a hereditary immunodeficiency.
21.Subjects with malignancies or with a history of malignancies with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
22.Significant trauma or major surgery within 4 weeks of screening visit.
23.Subjects requiring prohibited concomitant medications listed in Appendix 5 or subjects unwilling to discontinue herbal medications for at least 4 weeks prior to the first dose of study drug. Subjects

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified