A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of CNTO 136 (Sirukumab), a Human Anti-IL-6 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Rheumatoid Arthritis Despite DMARD Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,670
- 主要终点
- Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
研究概览
简要总结
The purpose of this study is to assess the efficacy of sirukumab as measured by the reduction of the signs and symptoms of rheumatoid arthritis (RA) and inhibition of radiographic progression in patients with active RA who are unresponsive to treatment with disease-modifying antirheumatic drugs (DMARD).
详细描述
Patients will be randomly assigned to treatment groups, and they and study personnel will not know the identity of the treatments given. Some patients will receive a placebo, which resembles a medication, but does not contain an active substance. This helps to determine if the study agent is effective. Patients will receive placebo or sirukumab by injection under the skin. The expected duration of the study is 120 weeks, which includes 104 weeks of treatment. Participants who complete participation in the study will be eligible for inclusion into the long-term safety and efficacy study, if enrollment at a participating site is available to them. If they do not participate in the long-term study, they will continue into the safety follow-up for approximately 16 weeks. The placebo-controlled portion of the study is through Week 52, when placebo patients will cross over to one of two sirukumab dose regimens. Patient safety will be monitored throughout the study.
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
- Double (Participant, Investigator)
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
- •Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
- •Have moderately to severely active RA with at least 6 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline
- •Have been unresponsive to single-agent or combination disease-modifying antirheumatic drugs (DMARD) therapy that includes methotrexate (MTX) or sulfasalazine (SSZ) due to lack of benefit after at least 12 weeks of DMARD, as assessed by the treating physician
- •If using oral corticosteroids, must be on a stable dose equivalent to less than or equal to 10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent
- •If using non nonsteroidal anti-inflammatory drug (NSAIDs) or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent
- •If using non-biologic DMARD such as MTX, SSZ, hydroxychloroquine, chloroquine, or bucillamine, must be on a stable dose for at least 4 weeks prior to the first administration of study agent and should have no serious toxic side effects attributable to the DMARD
排除标准
- •Has a history of intolerance to at least 2 or inadequate response to at least 1 anti-tumor necrosis factor alpha agent after 3 months of therapy
- •Has received infliximab, golimumab, adalimumab, or certolizumab pegol within 3 months of the first study agent administration
- •Has received etanercept or yisaipu within 6 weeks of the first study agent administration
- •Has a history of intolerance to tocilizumab that precluded further treatment with it, or inadequate response to 3 months of tocilizumab (anti-IL-6 receptor) therapy
- •Has used B-cell-depleting therapy (eg, rituximab) within 7 months of first study agent administration or have evidence during screening of abnormally low B cell level caused by previous B-cell depletion therapy
- •Has used anakinra within 4 weeks of first study agent administration
- •Has used any other biologic therapy for the treatment of RA within 3 months of the first study agent administration
- •Has received intra-articular (IA), intramuscular (IM), or intravenous (IV) corticosteroids for RA, including adrenocorticotrophic hormone during the 4 weeks prior to first study agent administration-
- •Has received leflunomide within 24 months before the first study agent administration and have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable. If a drug elimination procedure is performed during screening, the M1 metabolite should be measured and found to be undetectable
- •Has a history of cyclophosphamide or cytotoxic agent use
- •Has received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 4 weeks of the first study agent administration
- •Has received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half lives, whichever is longer, before the first study agent administration
研究组 & 干预措施
Placebo then Sirukumab 50 mg or Sirukumab 100 mg
干预措施: Placebo (Drug)
Placebo then Sirukumab 50 mg or Sirukumab 100 mg
干预措施: Sirukumab (Drug)
Sirukumab 100 mg
干预措施: Sirukumab (Drug)
Sirukumab 50 mg + Placebo
干预措施: Placebo (Drug)
Sirukumab 50 mg + Placebo
干预措施: Sirukumab (Drug)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 16
时间窗: Week 16
ACR 20 response is greater than or equal to (\>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and \>= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 52
时间窗: Baseline, Week 52
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
次要结局
- Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission at Week 24(Week 24)
- Percentage of Participants With Major Clinical Response (MCR) at Week 52(Week 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline, Week 24)
- Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Week 24(Week 24)
- Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Score of Less Than or Equal to 0.5(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Score at Week 24(Baseline, Week 24)
- Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Type of Damage (Erosion or JSN) at Week 24 and 52(Baseline, Week 24 and 52)
- Percentage of Participants With an American College of Rheumatology (ACR) 50 Response(Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With an American College of Rheumatology (ACR) 70 Response Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With an American College of Rheumatology (ACR) 90 Response Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With an American College of Rheumatology (ACR) 20 Response Through Week 52(Week 2, 4, 6, 8, 12, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Percentage of Participants With Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Response Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With Disease Activity Index Score 28 (DAS28) (C-reactive Protein (CRP) Remission Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI) Score Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With Simplified Disease Activity Index Based (SDAI-based) American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Percentage of Participants With Boolean-based American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission Through Week 52(Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Disease Activity Index Score 28 (DAS28) C-reactive Protein (CRP) Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 28, 32, 36, 40, 44, 48 and 52)
- Area Under the Curve (AUC) of Change From Baseline in HAQ-DI Score From Week 0 Through Week 24 and From Week 0 Through Week 52(Week 0 Through Week 24 and 52)
- Change From Baseline in Van Der Heijde-modified Sharpe (vdH-S) Sub-score by Region Hand or Feet and Type Erosion or JSN at Week 24 and 52(Baseline, Week 24 and 52)
- Percentage of Participants With Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) Greater Than Smallest Detectable Change (SDC) at Weeks 24 and 52(Weeks 24 and 52)
- Percentage of Participants With a Change of Less Than or Equal to 0 From Baseline in Van Der Heijde Modified Sharpe (vdH-S) Score at Weeks 24 and 52(Week 24 and 52)
- Change From Baseline in Van Der Heijde Modified Sharpe Score (vdH-S Score) by Reader at Weeks 24 and 52(Baseline, Weeks 24 and 52)
- Change From Baseline in Serum C-reactive Protein (CRP) Levels Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in the Duration of Morning Stiffness Through Week 52(Baseline, Week 2, 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Change From Baseline in Physical and Mental Component Summary Scores of 36-Item Short Form Health Survey (SF-36) at Weeks 24 and 52(Baseline, Week 24 and 52)
- Percentage of Participants With Greater Than or Equal to 4-Point Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 8, 16, 24, 36 and 52(Week 8, 16, 24, 36 and 52)
- Change From Baseline in Total Scores of Work Limitations Questionnaire (WLQ) Week 8, 16, 24, 36 and 52(Baseline, Week 8, 16, 24, 36 and 52)
- Change From Baseline in EuroQol Health State Visual Analogue Scale (EQ VAS)(Baseline, Week 8, 16, 24, 36 and 52)
- Change From Baseline in EuroQol EQ-5D-3L Descriptive System(at Week 8, 16, 24, and 52)