A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO COMPARE 3 DOSE LEVELS OF CP 690,550 VERSUS PLACEBO, ADMINISTERED ORALLY TWICE DAILY (BID) FOR 6 WEEKS, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS - N/A
- Conditions
- Rheumatoid ArthritisMedDRA version: 7.1Level: LLTClassification code 10039073
- Registration Number
- EUCTR2004-002846-36-DE
- Lead Sponsor
- Pfizer Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 312
- 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
- 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method