Rheumatoid Arthritis MedDRA version: 7.1 Level: LLT Classification code 10039073
Conditions
Interventions
Product Name: CP690,550
Product Code: CP690,550
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: CP690,550
Other descriptive name: (3R,4R)-4-methyl-3-(methyl-
Sponsors
Pfizer Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - The subject can give written informed consent. - Male or female subjects at least 18 years of age. However, for subjects >70 years old, the site must discuss subject eligibility with the study team to ensure that these subjects are sufficiently healthy to participate. - If the subject is a sexually active woman of childbearing potential, she and any male partner are required to simultaneously use 2 effective contraceptive methods, one of which must be a barrier (condoms, diaphragm or cervical cap) with spermicide. The other may be an oral or other acceptable contraceptive, which includes, but is not limited to: injectable, implanted or patch hormone therapy, IUD, or documented surgical sterilization for at least 4 weeks before screening, or partner vasectomy. She and any male partner must be willing to continue all of these contraceptive methods for 6 months after receiving study treatment. Within these limits, the specific forms of contraception employed are left to the discretion of the subject, the principal investigator, and/or the subject’s physician. - 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. - The subject has a diagnosis of RA based upon the American College of Rheumatology (ACR; formerly American Rheumatism Association) 1987 Revised Criteria,9 ie, fulfilling at least 4 of the following 7 criteria for at least 6 consecutive months preceding participation: 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 (PIP), 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. - The subject has active disease at both Screening and Baseline, as defined by both: · =9 joints tender or painful on motion, AND · =6 joints swollen; and fulfills 2 of the following 3 criteria at Screening: · at least 45 minutes duration of morning stiffness, · at least 28 mm/hour erythrocyte sedimentation rate (ESR) (Westergren method), · at least 10 mg/L C-reactive protein (CRP). - The subject meets ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II or III (Appendix A protocol). - Subjects must have had an inadequate response to, or discontinued for unacceptable toxicity to, either methotrexate, etanercept, infliximab, or adalimumab, according to the following criteria: · For methotrexate: an inadequate clinical response to doses of at least 15 mg weekly for at least 3 months, unless lower doses can be justified due to documented unacceptable toxicity. · For etanercept, infliximab, or adalimumab: either inadequate clinical response to an approved dose/regimen for at least 3 months or discontinuation for documented unacceptable toxicity. - The subject has discontinued all DMARD and immunosuppressive/immunomodulatory therapy for at least 4 weeks prior to first dose of study drug: · DMARDs: auranofin (oral gold), injectable gold (aurothioglucose or aurothio
Exclusion criteria
Exclusion criteria: - Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels <10 gm/dL or hematocrit <32% at screening visit or within the 3 months prior to randomization. - An absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3) at screening visit. - Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit. - Estimated GFR= 60 ml/min based on Cockcroft-Gault calculation (Appendix D). - Pregnant or lactating women. - Total bilirubin, AST or ALT more than 1.2 times the upper limit of normal at screening visit. - Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease. - History of an infected joint prosthesis at any time, with the prosthesis still in situ. - Current immunization with any live virus vaccine (eg, FluMist™) or history of immunization with any live virus vaccine within 1 month of randomization, or during the 6 weeks of treatment and the first 4 weeks of the follow-up period. - Current routine household contact with children who have received varicella or oral polio vaccine within 2 months of randomization, or during the 6 weeks of treatment and the first 4 weeks of the follow-up period. - History of any lymphoproliferative disorder (such as EBV-related lymphoproliferative disorder, as reported in some subjects on other immunosuppressive drugs), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease. - History of previously untreated infection with Mycobacterium tuberculosis (TB) or current treatment for same, as defined by any of the following: · A positive Mantoux Purified Protein Derivative (PPD) skin test, within the 3 months prior to randomization or · Chest radiograph, within the 3 months prior to randomization, that has changes suggestive of active TB infection - Subjects with clinically significant infections currently or within the past 6 months. - A subject who has received any experimental therapy for RA (within or outside a clinical trial) within 6 months prior to randomizations. However, subjects who have received an experimental NSAID or selective COX-2 inhibitor may participate once they have stopped the experimental therapy for more than 30 days. - Any prior treatment with lymphocyte-depleting agents/therapies. - Subjects with any condition possibly affecting oral drug absorption. - History of alcohol abuse with less than 6 months of sobriety. - History of drug abuse within 3 years. - Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect subject safety or interpretation of study results. - Unwillingness to refrain from consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication until the end of the treatment period. - Donation of blood in excess of 500 mL within 56 days prior to dosing. - Subjects with an oral temperature at Baseline visit of 38°C or higher. - Subjects with a first-degree relative with a hereditary immunodeficiency. - 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. - Recent (within 1 month of screening) significant trauma or major surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the efficacy of 3 dose levels of oral CP 690,550 monotherapy (5 mg, 15 mg, and 30 mg twice daily [BID]) versus placebo administered over 6 weeks for the treatment of the signs and symptoms of subjects with active RA.;Secondary Objective: The secondary objectives of this study are: -To evaluate the safety and tolerability over 12 weeks of CP 690,550 administered for 6 weeks, plus 6 weeks post-dosing follow up, to subjects with active RA. - To evaluate the pharmacokinetics of CP 690,550 and its correlation with clinical responses and with biomarkers of inflammation and immunosuppression. - To evaluate health status and functional status.;Primary end point(s): The primary endpoint is the American College of Rheumatology 20 (ACR 20) Responder rate at the Week 6 visit | — |
Countries
Germany, Italy, Spain
Outcome results
None listed