None listed
Conditions
Interventions
Group 1 Type of group
CP-690,550 5 mg 2 v / d + placebo in injection s.c. in alternate weeks
Group name:Group 5 Type of group
Placebo tablets 2 v / d + adalimumab injection 40 mg every two weeks
Sponsors
PFIZER S.A.,
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Rheumatoid arthritis with evidence of disease activity by joint counts and laboratory markers of inflammation as described in Section 4.1.1. • Ongoing treatment with an adequate and stable dose of 7.5 to 25 mg weekly of methotrexate, inclusive • Meet all eligibility criteria for ACR classification for RA as specified in the protocol • The patient must have active disease at both screening and baseline, as defined by having both: =6 tender/painful joints on motion (out of 68 joints assessed); and; =6 swollen joints (out of 66 joints assessed). • The patient must also have active disease, as defined by one of the following criteria at screening: a. Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr; or b. C reactive protein (CRP) >7 mg/L in the central laboratory. • The patient must meet Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.. • Background Methotrexate:All local standard of care practices for the administration of methotrexate, including laboratory testing, follow up care, contraindications, and folic acid administration should be performed according to local standards of care guidelines for methotrexate and folic acid therapy during study: • The patient must have taken oral or parenteral methotrexate continuously for at least 4 months prior to the first dose of study medication and be on a stable dose of 7.5 mg to 25 mg weekly, for at least 6 weeks prior to the first dose of study medication. Stable weekly doses less than 15 mg are allowed only in the presence of intolerance to or toxicity from higher doses or where higher doses would violate the local label. Doses higher than 25 mg weekly are not permitted under any circumstances. • The patient must have an inadequate clinical response to methotrexate defined as the presence of sufficient residual disease activity to meet the entry criteria. • A patient with a diagnosis of rheumatoid arthritis, on an appropriate regimen of methotrexate, who has discontinued other DMARD therapies • Evidence of a signed and dated informed consent document • Patient must be at least 18 years of age or older. • Patient has discontinued all disallowed concomitant medications for the required time prior to the first dose of study medication and is taking only those concomitant medications in doses and frequency allowed by the protocol. • Women of childbearing potential must test negative for pregnancy prior to enrollment in this study. • Sexually active women of childbearing potential and men whose partners are women of childbearing potential are required to use adequate contraceptive methods during participation in this study, as required for men and women on methotrexate therapy. • No history or evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB). • Patients 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.
Exclusion criteria
Exclusion criteria: • Pregnant or lactating females. • Blood dyscrasias within 3 months prior to the first dose of study medication, including confirmed: a. Hemoglobin 1.5 the upper limit of normal or any uncontrolled clinically significant laboratory abnormality. • Current or recent history of uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease. • History of any other autoimmune rheumatic 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 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 medication. • History of infection requiring antimicrobial therapy within 2 weeks prior to the first dose of study medication. • Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event. • Patients who have previously received adalimumab therapy for any reason. • Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label. Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure: • 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 medication or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks following discontinuation of study medication. • A patient with any condition possibly affecting oral drug absorption, • History of alcohol or drug abuse with less than 6 months of abstinence prior to first dose of study medication. • Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities which may affect patient safety or interpretation of study results. • 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, cervical carcinoma in situ. • Significant trauma or surgery procedure within 1 month prior to first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:ACR20 response: greater than or equal to (>=) 20% improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); 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: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; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores 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 Month 3 analysis. Measure:Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 3 Timepoints:Baseline, Month 3 ; Outcome name:DAS28-4 (ESR) calculado a partir de SJC y TJC utilizando el recuento de 28 articulaciones, la velocidad de sedimentacion globular (ESR) (milimetros por hora [mm / hora]) y la evaluacion global del paciente (PtGA) de la actividad de la enfermedad (puntaje transformado que varia de 0 a 10 ; una puntuacion mas alta indica una mayor afectacion debido a la actividad de la enfermedad). Rango de puntaje total: 0 a 9.4, puntaje mas alto indica mas actividad de la enfermedad. DAS28-4 (ESR) menor o | — |
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 the HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 1, 3, 9 and 12 Timepoints:Month 1, 3, 9 and 12 ; Outcome name:ACR50 response: >=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 the HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 1, 3, 6, 9 and 12 Timepoints:Month 1, 3, 6, 9 and 12 ; 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 the HAQ); and CRP. Measure:Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 1, 3, 6, 9 and 12 Timepoints:Month 1, 3, 6, 9 and 12 ; 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 implied moderate to high disease activity and 3.2 to 5.1 implied moderate to high disease activity and 3.2 to 5.1 implied moderate to high | — |
Countries
Australia, Bosnial and Herzegovina, Bulgaria, Canada, Chile, Costa Rica, Croatia, Czech Republic, Denmark, Dominican Republic, Finland, Germany, Korea South, Mexico, Philippines, Poland, Slovakia, Spain, Thailand, United Kindgdom, United States
Contacts
Public ContactPatricia Rodriguez
PFIZER S.A.
Outcome results
None listed