A Phase IIb, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Evaluate the Efficacy and Safety of Clazakizumab in Subjects With Moderate to Severe Active Rheumatoid Arthritis Who Have Experienced an Inadequate Response to TNF Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 143
- 试验地点
- 25
- 主要终点
- Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
研究概览
简要总结
The primary purpose of this study is to identify an appropriate dose of study medication.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of active Rheumatoid Arthritis (RA) by standard criteria (American Rheumatism association (ARA) [1987] or American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) [2010]) at least 16 weeks prior to screening
- •ACR global functional status class of 1 to 3
- •Documented evidence of inadequate response tumor necrosis factor (TNF) inhibitors
- •All subjects must have been receiving treatment with a minimum dose of 15 mg per week of Methotrexate for at least 12 weeks and at a stable dose for 28 days prior to screening. A dose as low as 10 mg Methotrexate is permitted if 15 mg could not be reached, due to toxicity. In Japan, Korea and Taiwan, a minimum dose of 7.5 mg per week is permitted. Additional treatment with Hydroxychloroquine or Chloroquine is permitted, if it is at a dose approved for the treatment of RA and the dose has been stable for at least 28 days prior to screening
- •Minimum of 6 swollen and 6 tender joints on a 66/68 joint count at screening and at baseline (Day 1)
- •Elevated High-sensitivity (hs) CRP and/or ESR
排除标准
- •Active serious infection
- •History of or active tuberculosis (TB)
- •Elevated liver function tests (LFTs)
研究组 & 干预措施
Arm 1: Clazakizumab (Dose # A) (Double-Blind)
Clazakizumab Dose # A injection by subcutaneous for 12 weeks + background Methotrexate
干预措施: Clazakizumab (Drug)
Arm 2: Clazakizumab (Dose # B) (Double-Blind)
Clazakizumab Dose # B injection by subcutaneous for 12 weeks + background Methotrexate
干预措施: Clazakizumab (Drug)
Arm 3: Clazakizumab (Dose # C) (Double-Blind)
Clazakizumab Dose # C injection by subcutaneous for 12 weeks + background Methotrexate
干预措施: Clazakizumab (Drug)
Arm 4: Placebo matching with Clazakizumab (Double-Blind)
Clazakizumab Dose # D injection by subcutaneous for 12 weeks + background Methotrexate
干预措施: Placebo (Matching with Clazakizumab) (Drug)
结局指标
主要结局
Change From Baseline in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) at Week 12
时间窗: Baseline and Week 12
DAS28-CRP describes severity of rheumatoid arthritis. The components of the joint count assessment are shoulder, elbow, wrist, metacarpophalangeal joints 1 through 5, proximal interphalangeal joints 1 through 5, and the knee joints on the right and left sides, whereby the number of affected joints, tender and swollen, respectively, are counted. The formula used to calculate the score is: DAS28-CRP=0.56 \\times \\sqrt{TEN28} + 0.28 \\times \\sqrt{SW28} + 0.36 \\times \\ln(CRP+1) + 0.014 \\times SA+0.96 with: TEN28: number of joints with tenderness upon touching SW28: number of swollen joints CRP: C-reactive Protein SA: subjective assessment of disease activity by the patient during the preceding 7 days on a scale between 0 and 100 ("0":no activity, "100": highest activity possible). DAS-CRP score range is 0.49 to 9.07 A DAS-CRP value \>5.1 corresponds to a high disease activity A DAS-28 reduction by 0.6 represents a moderate improvement. A reduction \>1.2 represents a major improvement
次要结局
- Percent of Participants With a DAS28-Erythrocyte Sedimentation Rate (ESR) <2.6(At week 12)
- American College of Rheumatology (ACR) 20/50/70 Response Rates(At week 12)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12(Baseline and week 12)
- Percent of Participants With a DAS28-C Reactive Protein (CRP) <2.6(At week 12)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12(Baseline and week 12)
- Boolean Remission at Week 12(At week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 12(Baseline and Week 12)