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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00619905
First received: February 8, 2008
Last updated: NA
Last verified: February 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: ACZ885
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Adverse events and infections occurrence throughout the study. [ Time Frame: throughout the study ]
  • 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 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)] . [ Time Frame: throughout the study ]
  • Disease Activity Score (DAS) at baseline and Days 43 and 113. [ Time Frame: 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. [ Time Frame: throughout the study ]
  • Serum concentrations of ACZ885 at each visit. [ Time Frame: throughout the study ]

Enrollment: 53
Study Start Date: December 2003
Study Completion Date: August 2005
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: ACZ885
Placebo Comparator: 2 Drug: ACZ885

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619905

Locations
Germany
Novartis Investigator Site
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
Netherlands
Novartis Investigator Site
Leiden, Netherlands
Novartis Investigator Site
Nijmegen, Netherlands
Switzerland
Novartis Investigator Site
Bern, Switzerland
Novartis Investigator Site
Geneva, Switzerland
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Novartis investigator site
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00619905     History of Changes
Other Study ID Numbers: CACZ885A2101
Study First Received: February 8, 2008
Last Updated: February 8, 2008
Health Authority: Germany: Paul-Ehrlich-Institut
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Switzerland: Swissmedic

Keywords provided by Novartis:
Rheumatoid Arthritis
Anti-interleukin-1 beta
ACZ885

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014