Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: ACZ885 (investigational); Placebo
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Rheumatoid Arthritis

Summary:

      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
    

Eligibility 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