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

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.

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: ACZ885

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Novartis Investigator Site
  • Hamburg, Germany
    • Novartis Investigator Site
  • Koeln, Germany
    • Novartis Investigator Site
  • Leipzig, Germany
    • Novartis Investigator Site
  • Munich, Germany
    • Novartis Investigator Site
  • Ratingen, Germany
    • Novartis Investigator Site
• Netherlands
  • Leiden, Netherlands
    • Novartis Investigator Site
  • Nijmegen, Netherlands
    • Novartis Investigator Site
• Switzerland
  • Bern, Switzerland
    • Novartis Investigator Site
  • Geneva, Switzerland
    • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: ACZ885
Placebo Comparator: 2	Drug: ACZ885

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Alten R, Gram H, Joosten LA, van den Berg WB, Sieper J, Wassenberg S, Burmester G, van Riel P, Diaz-Lorente M, Bruin GJ, Woodworth TG, Rordorf C, Batard Y, Wright AM, Jung T. The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10(3):R67. doi: 10.1186/ar2438. Epub 2008 Jun 5.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: February 8, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): February 21, 2008
• Last Update Submitted That Met QC Criteria: February 8, 2008
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; ACZ885; Anti-interleukin-1 beta
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CACZ885A2101