Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate

Study Overview
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Brief Summary
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This study assessed the long-term safety and tolerability of ACZ885 in patients with rheumatoid arthritis, as well as long-term efficacy, long-term preservation and/or improvement of joint structure and bone mineral density, and long term maintenance of health-related quality of life.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Cohort Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 (Anti-Interleukin-1Beta Monoclonal Antibody) in Patients With Active Rheumatoid Arthritis (RA) Despite Ongoing Treatment With Methotrexate (MTX) 15 mg or More Weekly for at Least 3 Months.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: ACZ885
* Drug: ACZ885


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged 18.5 - 65/75 years (depending on the dose group). Diagnosis of rheumatoid arthritis (ACR 1987 revised classification for criteria for RA) with a disease duration of at least 6 months prior to randomization. Active disease at screening and baseline evaluation (same evaluator) ) with more than 6 tender and 6 swollen joints of 28 examined (including any effused joint) and either a) Westergren erythrocyte sedimentation (ESR) ≥ 28 mm/hour, or b) CRP ≥ 6 mg/L. Patients should have failed at least 1 DMARD in the past, but should not be deemed refractory to all therapies Patients should have a current treatment regimen of ≥ 15 mg methotrexate/week and with the current dose stable for approximately 3 months. Patients were required to have an otherwise stable RA therapeutic regimen, consisting of either a stable dose of NSAIDs and/or a stable dose of oral corticosteroids (prednisone or equivalent < 10 mg daily) for at least 4 weeks prior to randomization. Exclusion Criteria: Previous treatment with anti-TNF-α antibody therapy (or other biological therapy) within appropriate timeframe (considering the half life of the compound) 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 OR require narcotic analgesics other than those accepted by the investigator for analgesia (e.g., codeine, tramadol, dextropropoxyphene) Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: ACZ885<br> <br> |
| Placebo Comparator: 2<br> | Drug: ACZ885<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and infections occurrence throughout the study. |  | throughout the study | 
| Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113). |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR response criteria [including joint counts, patient/investigator disease activity and pain assessment, acute phase reactants (ESR and CRP) and a Health Assessment Questionnaire (HAQ)] . |  | throughout the study | 
| Disease Activity Score (DAS) at baseline and Days 43 and 113. |  | throughout the study | 
| Quantification of IL-1B, IL-6, and C-reactive protein (CRP), matrix metalloproteinases (MMPs) 1 and 3, and c-telopeptide of Type I collagen (Crosslaps), at Week 7 versus baseline. |  | throughout the study | 
| Serum concentrations of ACZ885 at each visit. |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Anti-interleukin-1 beta, ACZ885