None listed
Conditions
Interventions
Group 1 Type of group
Oral tablets administered at 5 mg BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period. CP-690,550: Oral tablets administered at 5 mg BID daily through the end of the study during the double-blind, active-extension period.
Group name:Group 4 Type of group
Oral placebo tablets administered BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period. CP-690,550: Oral tablets administered at 10 mg BID daily through the end of the study during the double-blind, active-extension period.
Sponsors
PFIZER S.A.,
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Active, moderate to severe, rheumatoid arthritis with joint erosions or positive IgM Rheumatoid Factor or antibodies to cyclic citrullinated peptide • Be on an adequate and stable dose of methotrexate • Meet all eligibility criteria outlined below. • Meet the ACR classification criteria for the diagnosis of RA by satisfying at least four of the seven criteria. • Have at least three distinct joint erosions on posteroanterior (PA) hand and wrist or anteroposterior (AP) foot radiographs OR if this is not available, must have a positive IgM rheumatoid factor OR antibodies to cyclic citrullinated peptide • The patient must have active disease at both screening and baseline, as defined by having both =6 tender/painful joints on motion, and; =6 swollen joints. • At screening must have either Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr or C reactive protein (CRP) >7 mg/L • The patient must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA. • Must have taken oral or parenteral methotrexate continuously for at least 4 months and be on a stable weekly dose for at least 6 weeks. Weekly doses less than 15 mg are allowed only in the presence of intolerance or toxicity or where higher doses violate the local label. Doses higher than 25 mg weekly are not permitted. • Be on a stable dose of folic acid not less than 5 mg weekly, unless higher doses would violate the local label, for at least 4 weeks. • Must have an inadequate clinical response to methotrexate defined as the presence of sufficient residual disease activity to meet the entry criteria.
Exclusion criteria
Exclusion criteria: • Pregnancy or currently lactating. • Blood dyscrasias, including confirmed: a. Hemoglobin <9 g/dL or Hematocrit <30%; b. White blood cell count <3.0 x 10 to the power of 9/L; c. Absolute neutrophil count <1.2 x 10 to the power of 9/L; d. Platelet count <100 x 10to the power of 9/L. • Estimated GFR <40 ml/min based on Cockcroft Gault calculation. • AST or ALT greater than 1.5 times the upper limit of normal at screening or any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the patient’s participation in the study. • Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, metabolic, pulmonary, cardiac, or neurological disease. • History of any other rheumatic autoimmune disease, other than Sjogren’s syndrome • History of an infected joint prosthesis at any time, with the prosthesis still in situ. • History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease. • History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex. • History of any infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug. • History of any infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study drug. • Any prior treatment with non B cell specific lymphocyte depleting agents/therapies [eg, alemtuzumab (Campath®), alkylating agents (eg, cyclophosphamide or chlorambucil), total lymphoid irradiation, etc]. Patients who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline and have normal CD 19/20+ counts by FACS analysis. • Any patient who has been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study drug or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks following discontinuation of study drug. • A patient with any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary. • History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study drug. • Screening 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety. • A patient with a first degree relative with a hereditary immunodeficiency. • A patient with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. • Significant trauma or surgery procedure within 1 month prior to first dose of study drug. • A patient requiring prohibited concomitant medications including prohibited dietary
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis. Measure:Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 6 Timepoints:Month 6 ; Outcome name:mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis. Measure:Changes From Baseline in Modified Total Sharp Score (mTSS) at Month 6 Timepoints:Baseline, Month 6 ; Outcome name:HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom, arise, eat, walk, reach, grip, hygiene and common activities over past week. Each item scored on 4-point scale, 0 to 3: 0=no difficulty; 1=some difficulty;2=much difficulty; 3=unable to do. Overall score was computed as sum of domain sc ores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:ACR20 response: >=20% improvement in tender joint count; >=20% improvement in swollen joint count; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) at Month 1, 3, 9, 12, 15, 18, 21 and 24 Timepoints:Month 1, 3, 9, 12, 15, 18, 21, 24 ; Outcome name:ACR50 response: greater than or equal to >=50% improvement in tender joint count; >=50% improvement in swollen joint count; and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) at Month 1, 3, 6, 9, 12, 15, 18, 21 and 24 Timepoints:Month 1, 3, 6, 9, 12, 15, 18, 21 and 24 ; Outcome name:ACR70 response: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) at Month 1, 3, 6, 9, 12, 15, 18, 21 and 24 Timepoints:Month 1, 3, 6, 9, 12, 15, 18, 21 and 24 ; Outcome name:DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) =3.2 to 5.1 indicated moderate to high disease activity and 3.2 to 5 | — |
Countries
Australia, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Greece, India, Japan, Korea South, Mexico, Poland, Taiwan, Ukraine, United States, Venezuela
Contacts
Public ContactPatricia Rodriguez
PFIZER S.A.
Outcome results
None listed