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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
- •2 months washout prior to screening for etanercept or adalimumab
- •3 months washout prior to screening for infliximab
- •3 months washout prior to screening for rituximab
- •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
研究组 & 干预措施
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.
干预措施: ACZ885 (investigational) (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA)
时间窗: 6 weeks and 12 weeks
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))
次要结局
- Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI)(6 weeks and 12 weeks)
- Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28)(6 weeks and 12 weeks)