Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis

Other protocol-defined inclusion/exclusion criteria may apply

CORE STUDY

Inclusion Criteria

Core Study Inclusion Criteria At Screening

• Cooperative male or non-pregnant, non-lactating female patients at least 18 years of age who signed an informed consent before the initiation of any study procedure.
• Diagnosis of rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR) 1987 revised criteria and with symptoms for at least 3 months before randomization.
• Functional status class I, II or III classified according to the ACR 1991 revised criteria.
• Patients treated with methotrexate (MTX) at the maximum tolerated (≤25 mg/week) and stable dose of ≥7.5 mg/week for at least 12 weeks before randomization.
• Patients who had failed any disease-modifying antirheumatic drugs (DMARDs) (including biologic agents and any DMARD used in combination with MTX) were allowed.
• For patients with previous treatment of biological therapy, the following wash-out periods were required before randomization:
• 3 days for Kineret™ (anakinra) - with a terminal half-life of 4 to 6 hours (s.c. route).
• 4 weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours (s.c.

route).

• 8 weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9. 5 days (intravenous (i.v.) infusion).
• 12 weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks) (subcutaneous (s.c.) route).
• 12 weeks for Orencia® (abatacept) - with a terminal half-life of 13.1 (8-25) days (i.v. infusion).
• 26 weeks for any other biologic - or 10 half-lives, whichever was longer.
• Patients who took systemic corticosteroids had to be on a stable dose of ≤10 mg/d prednisone or equivalent for at least 4 weeks before randomization.
• Patients who were regularly taking non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors or paracetamol/ acetaminophen as part of their RA therapy must have been on a stable dose for at least 4 weeks before randomization. Patients taking NSAIDs or COX-2 inhibitors or paracetamol/acetaminophen as needed within 2 weeks before randomization had to stop their medication at least 24 hours before an ACR visit (i.e. Visits 3, 7, 8, 10 and 12 [End of Study]). Patients taking folic acid supplementation had to be on stable dose for at least 4 weeks before randomization.
• Patients with a history of immunization for Influenza (within past 12 months) and Pneumococcal vaccination (within 4 years) were included. If not already immunized, vaccination was completed when medically indicated (only during flu season for influenza) and such patients were included after approximately a 3 week window post-immunization to allow immunity to develop for vaccine.
• Weight ≥45 kg and body mass index (BMI) <34.0
• Women of non-child-bearing potential, defined as all women physiologically not capable of becoming pregnant.

Core Study Inclusion criteria At Baseline (Visit 3)

• Disease activity criteria of ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints.
• One of the following also had to be present:
• High-sensitive C-Reactive Protein (hsCRP) concentration ≥10 mg/L
• Erythrocyte Sedimentation Rate (ESR) ≥28 mm/1st hr
• a. + b. based on screening values.

EXCLUSION

• History of hypersensitivity to study drug or to molecules with similar structures.
• Any therapy by intra-articular injections (e.g. corticosteroid) required for treatment of acute RA flare within 4 weeks before randomization.
• Current use of DMARDs other than MTX. DMARDs included but were not limited to: biologic agents, thiolates (D-penicillamine, thiopronine), sulfasalazine, gold compounds, antimalarials, cyclosporine A, azathioprine, leflunomide, and alkylating agents such as cyclophosphamide.
• If a patient had been discontinued from DMARDs, the patient should have been off the agent for at least 4 weeks, except leflunomide which was 8 weeks.
• Patients with evidence of active pulmonary di