rheumatism
Conditions
Interventions
Patients will receive AIN457 or placebo. Depending on the moment of inclusion
the patients will receive in part I: single dose 0.3 mg/kg - 10 mg/kg or MTD,
in part II: 2 doses 1.0 mg/kg - 10 mg/kg o
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male and female patients aged 18-75 years. 2. Diagnosis of active rheumatoid arthritis of stages I, II or III. Disease duration of at least 6 months prior to randomization. 3. (Relatively stable) active disease at screening and baseline evaluation: * 6 tender and * 6 swollen joints of 28 examined and either a) ESR * 28 mm/hour, or b) CRP * 1.5 mg/L. Part 1 of the study at the 0.3 mg/kg and 1 mg/kg may enroll patients with * 3 tender and/or swollen joints, with no requirements for ESR and CRP since there will be no efficacy measurements done at those dose levels. 4. Patients must be on a current treatment with methotrexate * 25 mg/week and with the current dose stable for at least 3 months. Prior treatment with 1*3 DMARDs. Patients should have failed at least 1 DMARD including methotrexate. 5. Patients with a total white cell count, platelet count, hemoglobin and hematocrit values that are clinically acceptable for patients with RA 6. Patients with a history of immunization for Influenza (within past 12 months) and Pneumococcal vaccination (within 4 years).
Exclusion criteria
Exclusion criteria: 1. Current treatment with anti-TNF-* or anti IL-1 therapy (or other biological therapy), or immunosuppressive agents. 2. 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, or standard washout procedure. Importantly, discontinuation should not be undertaken only for the purposes of participation in this study. 3. Patients with congestive heart failure (NYHA > III) or poorly controlled diabetes mellitus (HbA1c value * 10%). 4. Patients who have received intra-articular or systemic corticosteroid injections for treatment of acute RA flare within four weeks prior to randomization OR who require strong narcotic analgesics that can mask the pain symptoms required as an entry criterion. 5. Presence of major chronic inflammatory autoimmune diseases that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study. 6. History of renal trauma, glomerulonephritis or patient with one kidney. 7. Treatment with an investigational agent within 12 weeks prior to enrollment. 8. Presence of severe physical incapacity (Steinbrocker Class IV) 9. Pregnant or breastfeeding women. 10. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing 11. A positive HIV, hepatitis B, hepatitis C or tuberculin test result. 12. 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. 13. History of severe hypersensitivity to any biological agents, a history of serious allergic reaction, collagen disease, neurological disease. 14. History of any joint surgery in past 8 weeks or planned surgery within next 5 months. 15. History of malignancy. 16. History or evidence of drug or alcohol abuse within the 6 months prior to dosing. 17. Presence of clinically significant proteinuria, creatinine, active sediments, casts or WBCs in urine. 18. 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 |
|---|---|
| Safety and tolerability: vital signs, ECG, laboratory results, adverse events and concomitant medications / significant non-drug therapies. Pharmacokinetic data Pharmacodynamic data: ACR20, ACR50 and ACR70 responders and DAS score. After each cohort has completed treatment, the clinical team will review the safety and pharmacokinetic data available. | — |
Secondary
| Measure | Time frame |
|---|---|
| biomarkers, immunogenicity of IV AIN457, total and free IL 17 in blood, pharmacogenetic assessments and pharmacogenomic assessments | — |
Countries
Netherlands
Outcome results
None listed