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

This study has been terminated.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00505089
First received: July 19, 2007
Last updated: August 24, 2009
Last verified: August 2009
  Purpose

This study will investigate the pharmacokinetic (PK) / total IL-1beta pharmacodynamic (PD) relationship in joint fluids of patients with rheumatoid arthritis (RA) treated with different doses of ACZ885 and to evaluate the impact of the subcutaneous (s.c.) versus intravenous (i.v.) route of administration.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Exploratory, Open Label Pharmacokinetic - Pharmacodynamic Study to Compare Subcutaneous Versus Intravenous Administration of ACZ885 in Adult Patients With Established Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • - Pharmacokinetic/total IL-1beta pharmacodynamic relationship in joint fluids of patients with rheumatoid arthritis treated with different doses of ACZ885 - Impact of the subcutaneous versus intravenous administration [ Time Frame: End of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • - PK/PD of ACZ885 in patient serum and to evaluate impact of s.c. versus i.v. administration - Efficacy via response to treatment (ACR 20% improvement [ACR 20],50,70 & 90) [ Time Frame: Days 8,15,29,43 and study completion ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: August 2007
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ACZ885 10mg/kg subcutaneous
Drug: ACZ885
Experimental: 2
ACZ885 5mg/kg intravenous
Drug: ACZ885
Experimental: 3
ACZ885 2mg/kg subcutaneous
Drug: ACZ885
Experimental: 4
ACZ885 1mg/kg intravenous
Drug: ACZ885

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients aged 18 - 75 years (inclusive).
  • Body weight must be between 50 and 100 kg (inclusive).
  • Post-menopausal or surgically sterile female patients. Women of child-bearing potential if already on a stable dose of methotrexate and are practicing effective contraception for at least 3 months prior to screening, have a negative pregnancy test at screening and baseline, and are willing to use 2 forms of contraception including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study. Male patients must be willing to use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
  • Diagnosis of Rheumatoid Arthritis, classified by ARA (American Rheumatism Association) 1987 revised criteria (Appendix 2). Disease duration of at least 6 months prior to randomization is essential.
  • Functional status class I, II or III classified according to the ACR (American College of Rheumatology) 1991 revised criteria (Appendix 3).
  • Active disease at screening and baseline (Day 1 predose) evaluation (same evaluator): ≥ 6 tender and ≥ 6 swollen joints of 28 examined (including any effused joint) and either a) Westergren erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour, or b) C-reactive protein (CRP) ≥ 1.0 mg/dL.
  • 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". Patients should be on a current treatment with methotrexate ≤ 25 mg/week and with the current dose stable for at least 3 months. 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).
  • Patients with a total white cell count and platelet count clinically acceptable for patients with RA; hemoglobin must be ≥ 10 g/dL and hematocrit ≥ 30% at screening and baseline.

Exclusion Criteria:

  • Previous treatment with anti-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 for lack of efficacy or toxicity, the patient should be at least 1 month off the agent and the effects of that agent should have dissipated according to the recognized duration of effect (e.g., sulfasalazine, hydroxychloroquine), or standard washout procedure (cholestyramine for leflunomide). Importantly, discontinuation should not be undertaken only for the purposes of participation in this study.
  • 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.
  • Presence of or history of Major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or systemic lupus erythematosus.

Renal trauma, glomerulonephritis or patient with one kidney. Patients with congestive heart failure (New York Heart Association class > III), QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded. A positive HIV test result, Hepatitis B surface antigen or Hepatitis C test result. Significant illness within 2 weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study. Hypersensitivity to any biological agents, serious allergic reaction, collagen disease, neurological disease (including demyelinating disease). Any joint surgery in past 8 weeks or planned surgery within next 5 months. Cancer (other than basal cell cancer or adequately treated carcinoma-in-situ of the cervix). Drug or alcohol abuse within the 12 months prior to dosing or evidence of such indicated by the laboratory assays conducted during the screening or baseline evaluations. Underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or gastrointestinal conditions which places the patient at unacceptable risk for participation in a study of an immunomodulatory therapy.

  • Treatment with an investigational agent within 12 weeks prior to enrollment or longer if required by local regulation.
  • Pregnant or breastfeeding women.
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing

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: NCT00505089

Locations
Belgium
Novartis Investigative site
Antwerp, Belgium
Novartis Investigator Site
Liege, Belgium
Germany
Novartis Investigative site
Berlin, Germany
Novartis Investigator Site
Berlin, Germany
Novartis Investigator Site
Hannover, Germany
Novartis Investigator Site
Leipzig, Germany
Netherlands
Novartis investigative site
Leiden, Netherlands
Poland
Novartis Investigative Site
Grodzisk Mazowiecki, Poland
Novartis Investigator Site
Poznan, Poland
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Investigative site
  More Information

No publications provided

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00505089     History of Changes
Other Study ID Numbers: CACZ885A2206
Study First Received: July 19, 2007
Last Updated: August 24, 2009
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
pharmacokinetic, pharmacodynamic, subcutaneous, intravenous, ACZ885, patients, rheumatoid, arthritis.

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

ClinicalTrials.gov processed this record on November 25, 2014