A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED ACTIVE COMPARATOR, MULTICENTER STUDY TO COMPARE 5 DOSE REGIMENS OF CP-690,550 AND ADALIMUMAB VERSUS PLACEBO, ADMINISTERED FOR 6 MONTHS IN THETREATMENT OF SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS - not applicable
- Conditions
- Rheumatoid ArthritisMedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2007-002066-35-HU
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
1. Evidence of a signed and dated informed consent document(s) indicating that the subject has been informed of all pertinent aspects of the study.
2. Subjects must be at least 18 years of age.
3. 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, from the list of effective contraceptives found in Section 4.4
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 (ACR; formerly American Rheumatism Association) 1987 Revised Criteria5, 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 (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.
6. The subject has active disease at both Screening and Baseline, as defined by both:
a. =6 joints tender or painful on motion, AND
b. =6 joints swollen;
and fulfills 1 of the following 2 criteria at Screening:
i. Erythrocyte sedimentation rate (ESR) (Westergren method) above the upper limit of normal in the local laboratory
ii. 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 1).
8. 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, or as defined in Concomitant Medications (Section 5.5).
9. Subjects must have failed an adequate study of therapy with at least 1 DMARD due to lack of efficacy or toxicity. See inclusion criteria 10 and exclusion criteria 1 and 12.
10. Subjects having received the following treatment regimens are eligible, provided 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:
DMARDS – leflunomide (Arava® ) (see additional washout information for leflunomide in Appendix 10), auranofin (oral gold), injectable gold (aurothioglucose or aurothiomalate), methotrexate, sulfasalazine, and d-penicillamine, minocycline; etanercept (Enbrel®); anakinra (Kineret®);
Immunosuppressive/Immunomodulatory therapies -azathioprine,
cyclosporine, and PROSORBA® device/column;
NSAIDs - any experimental NSAIDs or experimental selective COX-2
inhibitors;
Other - herbal medications, immunization with any live virus vaccination (eg, FluMist™), intra-articular, intramuscular, or intravenous corticosteroids;
b. Within 8 weeks of first dose:
infl
1. Subjects who discontinued any previous TNFi therapy for either lack of efficacy or adverse events. Subjects who previously received adalimumab therapy for any reason are not allowed in the study.
2. Subjects with evidence of hematopoietic disorders:
a. Hemoglobin levels <9.0 gm/dL or hematocrit <30% at screening visit or within the 3 months prior to first study dose.
b. An absolute white blood cell count of <3.0 x 109/L or absolute neutrophil count of <1.2 X 109/L at screening visit or within the 3 months prior to first study dose.
c. Thrombocytopenia, as defined by a platelet count <100 x 109/L at screening visit or within the 3 months prior to first study dose.
3. Estimated GFR =50 ml/min based on Cockcroft-Gault calculation.
4. Pregnant or lactating women.
5. Total bilirubin, AST or ALT more than 2 times the upper limit of normal at screening visit.
6. Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
7. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
8. Current routine household contact with children who have received varicella or oral polio vaccine within 2 months prior to first study dose, or during the 24 weeks of treatment and for 4 weeks following completion of the study.
9. History of any lymphoproliferative disorder, history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease.
10. Evidence of active or latent infection with Mycobacterium tuberculosis, as defined by any of the following:
a. A subject has a positive Mantoux Purified Protein Derivative (PPD) skin test result of =5 mm of induration within the 3 months prior to screening, OR
b. A subject is immunoreactive for TB using an ex vivo method, OR
c. A subject has a chest radiograph that has changes suggestive of active TB infection.
11. Subjects with clinically significant infections currently or within 6 months of first dose of study drug (eg, those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections), 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 study or any infection requiring antimicrobial therapy within 2 weeks of screening.
12. Any prior treatment with lymphocyte-depleting agents/therapies (such as
CamPath®[alemtuzab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc). Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least 1 year prior to first dose (see Appendix 10 for wash out procedure).
13. Subjects with any condition possibly affecting oral drug absorption (eg,
bariatric/obesity surgery [such as gastric bypass or gastric banding], gastrectomy, or clinically significant diabetic gastroenteropathy).
14. History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug.
15. Screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results.
16. Donation of blood in excess of 500 mL within 2 months prior to first study dose.
17. Subjects
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