Rheumatoid Arthritis MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male and female patients aged 18 - 75 years (inclusive). Body weight must be between 50 and 100 kg (inclusive). Post-menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are already on a stable dose of methotrexate, if they are practicing effective contraception for at least 3 months prior to screening, have a negative pregnancy test at screening and baseline, and are willing to use 2 forms of contraception including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study. Male patients must be willing to use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study. Diagnosis of RA, classified by ARA 1987 revised criteria. Disease duration of at least 6 months prior to randomization is essential. Functional status class I, II or III classified according to the ACR 1991 revised criteria. Active disease at screening and baseline (Day 1 predose) evaluation (same evaluator): = 6 tender and = 6 swollen joints of 28 examined (including any effused joint) and either a) Westergren erythrocyte sedimentation rate (ESR) = 28 mm/hour, or b) C-reactive protein (CRP) = 1.0 mg/dL. Prior treatment with 1–3 disease-modifying anti-rheumatic drugs (DMARDs) - Patients should have failed at least 1 DMARD but should not be deemed “refractory to all therapies”. Patients should be on a current treatment with methotrexate = 25 mg/week and with the current dose stable for at least 3 months. All patients will take folic acid 1 mg daily, or 5 mg weekly post MTX dose, to minimize toxicity, according to local guidelines. In addition to methotrexate, patients may be on either a stable dose of non-steroidal anti-inflammatory drugs (NSAIDs) and/or a stable dose of oral corticosteroids (prednisone or equivalent = 10 mg daily) for at least 4 weeks prior to randomization. Patients who failed any DMARDs (including biologic agents and any DMARD used in combination with MTX) will be allowed. Negative purified protein derivative (PPD) tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice) (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Previous treatment with anti-TNF-a or anti IL-1 therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial. 2 months washout prior to screening for Enbrel® (etanercept) or Humira® (adalimumab) 3 months washout prior to screening for Remicade® (infliximab) 3 months washout prior to screening for Rituxan® (rituximab) 1 month washout prior to screening for cyclosporine, mycophenolate and tacrolimus. If patient has been discontinued from other DMARDs for lack of efficacy or toxicity, the patient should be at least 1 month off the agent and the effects of that agent should have dissipated according to the recognized duration of effect (e.g., sulfasalazine, hydroxychloroquine), or standard washout procedure (cholestyramine for leflunomide). Importantly, discontinuation should not be undertaken only for the purposes of participation in this study. Patients with congestive heart failure (New York Heart Association class > III), QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded. Patients who have received intra-articular or systemic corticosteroid injections having been required for treatment of acute RA flare (not being part of a regular therapeutic regimen) within four weeks prior to randomization. Presence of or history of major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or systemic lupus erythematosus. History of renal trauma, glomerulonephritis or patient with one kidney. Treatment with an investigational agent within 12 weeks prior to enrollment or longer if required by local regulation. Pregnant or breastfeeding women. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing A positive HIV (ELISA and Western blot) test result, Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study. History of hypersensitivity to any biological agents (antibody or soluble receptor), a history of serious allergic reaction, collagen disease, neurological disease (including demyelinating disease). History of any joint surgery in past 8 weeks or planned surgery within next 5 months. History of malignancy (other than basal cell carcinoma or adequately treated carcinoma-in-situ of the cervix). History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such indicated by the laboratory assays conducted during the screening or baseline evaluations. Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in a study of an immunomodulatory therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish a pharmacokinetic (PK) / total IL-1beta pharmacodynamic (PD)relationship in joint fluids of patients with rheumatoid arthritis (RA) treated with different doses and to evaluate the impact of the subcutaneous (s.c.) versus intravenous (i.v.) route of administration.;Secondary Objective: Evaluate PK/PD in sera of patients with RA treated with different doses (evaluate impact of s.c. versus i.v. route of administration). Evaluate efficacy by assessing response to treatment (ACR20, 50, 70, 90) in patients at Days 8, 15, 29, 43 and study completion. Evaluate efficacy by assessing response to treatment using the Simplified Disease Activity Index and Disease Activity Score 28 scoring at Days 8, 15, 29, 43 and study completion. Establish biomarker profile at baseline and after treatment contributing to the identification of patients responding to treatment. Assess overall safety and tolerability and in particular infection occurrence and evaluate immunogenicity. Assess change in health-related quality of life at Days 8, 15, 29, 43 and study completion using HAQ®, SF-36®, and FACIT-F©.;Primary end point(s): See Primary Objectives. | — |
Countries
Belgium, Germany
Outcome results
None listed