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.
1 other identifier
interventional
53
3 countries
10
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 rheumatoid-arthritis
Started Dec 2003
Typical duration for phase_1 rheumatoid-arthritis
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2005
CompletedFirst Submitted
Initial submission to the registry
February 8, 2008
CompletedFirst Posted
Study publicly available on registry
February 21, 2008
CompletedFebruary 21, 2008
February 1, 2008
1.7 years
February 8, 2008
February 8, 2008
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (4)
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
Study Arms (2)
1
EXPERIMENTAL2
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartislead
Study Sites (10)
Novartis Investigator Site
Berlin, Germany
Novartis Investigator Site
Cologne, Germany
Novartis Investigator Site
Hamburg, Germany
Novartis Investigator Site
Leipzig, Germany
Novartis Investigator Site
Munich, Germany
Novartis Investigator Site
Ratingen, Germany
Novartis Investigator Site
Leiden, Netherlands
Novartis Investigator Site
Nijmegen, Netherlands
Novartis Investigator Site
Bern, Switzerland
Novartis Investigator Site
Geneva, Switzerland
Related Publications (1)
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.
PMID: 18534016DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Novartis
Novartis investigator site
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
February 8, 2008
First Posted
February 21, 2008
Study Start
December 1, 2003
Primary Completion
August 1, 2005
Study Completion
August 1, 2005
Last Updated
February 21, 2008
Record last verified: 2008-02