Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00504595
First received: July 19, 2007
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

This study was intended to assess the safety, efficacy, and response to treatment using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) and to investigate a potential biomarker profile in adult patients with established rheumatoid arthritis


Condition Intervention Phase
Rheumatoid Arthritis
Drug: ACZ885 (investigational)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR20) and to Determine a Biomarker Profile in Adult Patients With Established Rheumatoid Arthritis Responding to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) as Compared to Healthy Subjects Exposed to ACZ885

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA) [ Time Frame: 6 weeks and 12 weeks ] [ Designated as safety issue: No ]

    At each post-dose visit, an ACR20 responder was defined as someone who achieved at least 20% improvement in the tender and the swollen 28-joint count, and 20% improvement in at least 3 of the following 5 measures::

    • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
    • Patient's global assessment of disease activity (VAS 100 mm)
    • Physician's global assessment of disease activity (VAS 100 mm)
    • Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
    • Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))


Secondary Outcome Measures:
  • Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI) [ Time Frame: 6 weeks and 12 weeks ] [ Designated as safety issue: No ]
    SDAI is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). SDAI measures the high sensitivity C-reactive protein (hsCRP) level, patient's global disease activity (PGDA) and evaluator's global disease activity (EGDA). PGDA and EGDA are measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. SDAI = tender28 + swollen28 + CRP + (PGDA/10) + (EGDA/10). Lower scores indicate less disease activity.

  • Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28) [ Time Frame: 6 weeks and 12 weeks ] [ Designated as safety issue: No ]
    DAS28 is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). DAS28 measures the C-reactive protein (CRP) (in mg/L) and the patient's general health (GH). GH is measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. DAS28 = 0.56*√(tender28) + 0.28*√(swollen28) + 0.36*log_e(CRP+1) + 0.014*PGDA + 0.96. Lower scores indicate less disease activity.


Enrollment: 80
Study Start Date: May 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACZ885

Healthy Volunteers: Single administration of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1.

Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.

Drug: ACZ885 (investigational)
The ACZ885 was supplied in 6 mL colorless glass vials each containing nominally 150 mg ACZ885 (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.
Other Name: Canakinumab
Placebo Comparator: Placebo

Healthy Volunteers: Single administration of 600 mg of Placebo Intravenous (IV) on Day 1.

Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of Placebo Intravenous (IV) on Day 1, Day 15, and Day 43.

Drug: Placebo
Matching placebo of ACZ885 was supplied in the form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

RA patients:

  • Male and female patients aged 18 - 75 years (inclusive).
  • Body weight between 50 and 100 kg (inclusive).
  • Post menopausal or surgically sterile female patients are allowed. Female patients of child-bearing potential may participate if they are already on a stable dose of methotrexate. Additional birth control details to be provided at screening. Male patients must use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
  • Diagnosis of RA, classified by American Rheumatism Association 1987 revised criteria. Disease duration of at least 6 months is essential.
  • Functional status class I, II or III classified according to the American College of Rheumatology 1991 revised criteria.
  • Active disease evaluation (≥ 6 tender and ≥ 6 swollen joints)
  • Prior treatment with 1-3 disease-modifying anti-rheumatic drugs (DMARDs) - Patients should have failed at least 1 DMARD but should not be deemed "refractory to all therapies". It is expected that patients are on a current treatment with methotrexate ≤ 25 mg/week and with the current dose stable for at least 3 months, however patients who did not tolerate MTX may also be considered. All patients will take folic acid 1 mg daily, or 5 mg weekly post MTX dose, to minimize toxicity, according to local guidelines. In addition to methotrexate, patients may be on either a stable dose of non-steroidal anti-inflammatory drugs (NSAIDs) and/or a stable dose of oral corticosteroids (prednisone or equivalent ≤ 10 mg daily) for at least 4 weeks prior to randomization. Patients who failed any DMARDs will be allowed.
  • Negative purified protein derivative (PPD) tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice).

Exclusion Criteria:

RA patients:

  • Previous treatment with anti-Tumor Necrosis Factor (TNF)-α or anti IL-1 therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.

    1. 2 months washout prior to screening for etanercept or adalimumab
    2. 3 months washout prior to screening for infliximab
    3. 3 months washout prior to screening for rituximab
    4. 1 month washout prior to screening for cyclosporine, mycophenolate and tacrolimus.
  • If patient has been discontinued from other DMARDs (disease modifying antirheumatic drugs) for lack of efficacy or toxicity, the patient should be at least 1 month off the agent.
  • Patients with congestive heart failure, QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded.
  • 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 4 weeks prior to randomization.
  • Exclusion criteria 2-6 of the Health Volunteer section also applies here.

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: NCT00504595

Locations
Russian Federation
Novartis Investigative site
Moscow, Russian Federation
Spain
Novartis investigative site
Barcelona, Spain
Switzerland
Novartis Investigative site
Bern, Switzerland
Turkey
Novartis investigative site
Istanbul, Turkey
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigator site
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00504595     History of Changes
Other Study ID Numbers: CACZ885A2207
Study First Received: July 19, 2007
Results First Received: January 20, 2011
Last Updated: August 2, 2012
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014