Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ACZ885
ACZ885
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Anti-interleukin-1 beta, ACZ885
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
- Novartis Investigator Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Outcomes
Primary Outcome Measures
Adverse events and infections occurrence throughout the study.
Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113).
Secondary Outcome Measures
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)] .
Disease Activity Score (DAS) at baseline and Days 43 and 113.
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.
Serum concentrations of ACZ885 at each visit.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00619905
Brief Title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2008
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
August 2005 (Actual)
Study Completion Date
August 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Anti-interleukin-1 beta, ACZ885
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ACZ885
Intervention Type
Drug
Intervention Name(s)
ACZ885
Primary Outcome Measure Information:
Title
Adverse events and infections occurrence throughout the study.
Time Frame
throughout the study
Title
Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113).
Time Frame
throughout the study
Secondary Outcome Measure Information:
Title
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)] .
Time Frame
throughout the study
Title
Disease Activity Score (DAS) at baseline and Days 43 and 113.
Time Frame
throughout the study
Title
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.
Time Frame
throughout the study
Title
Serum concentrations of ACZ885 at each visit.
Time Frame
throughout the study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Novartis investigator site
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigator Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigator Site
City
Hamburg
Country
Germany
Facility Name
Novartis Investigator Site
City
Koeln
Country
Germany
Facility Name
Novartis Investigator Site
City
Leipzig
Country
Germany
Facility Name
Novartis Investigator Site
City
Munich
Country
Germany
Facility Name
Novartis Investigator Site
City
Ratingen
Country
Germany
Facility Name
Novartis Investigator Site
City
Leiden
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Nijmegen
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Bern
Country
Switzerland
Facility Name
Novartis Investigator Site
City
Geneva
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
18534016
Citation
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.
Results Reference
derived
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate
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