A Phase 2a Multicenter, Randomized, Double Blind, Parallel, Proof of Concept Study Evaluating the Efficacy and Safety of Nipocalimab and Certolizumab Combination Therapy in Participants With Active Rheumatoid Arthritis Despite Prior Treatment With Advanced Therapies (bDMARD or tsDMARD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 32
- 主要终点
- Change From Baseline in Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) at Week 12
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of combination therapy with nipocalimab and certolizumab compared to certolizumab monotherapy.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of rheumatoid arthritis (RA) and meeting the 2010 American college of rheumatology (ACR) or European League Against Rheumatism (EULAR) criteria for RA for at least 3 months before screening
- •Has moderate to severe active RA as defined by persistent disease activity with at least 6 of 66 swollen joints and 6 of 68 tender joints at the time of screening and at baseline
- •Is positive for anti-citrullinated protein antibodies (ACPA) or rheumatoid factor (RF) by the central laboratory at the time of screening
- •Has C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram per deciliter (mg/dL) by the central laboratory at the time of screening
- •If has received prior biological disease-modifying antirheumatic drugs (bDMARDs) (or biosimilars) other than anti-tumor necrosis factor (anti-TNF) agent in RA, has demonstrated inadequate response (IR) or intolerance to the therapy based on one of the following:
- •IR to at least 1bDMARD (or the biosimilars) other than anti-TNF agents, as assessed by the treating physician, after at least 12 weeks of therapy including but not limited to abatacept, anakinra, tocilizumab, and sarilumab or at least 16 weeks of therapy with rituximab Documented IR may include inadequate improvement or loss in response after initial improvement in joint counts or other parameters of disease activity
- •Intolerance to bDMARD (or biosimilars) other than anti-TNF agent, as assessed by the treating physician. Documented intolerance includes side effects and injection or infusion reactions
- •If has received prior anti-TNF agent (including biosimilars), has demonstrated IR to >=1 anti-TNF agent (including biosimilars), as assessed by the treating physician:
- •After at least 12 weeks dosage of etanercept, adalimumab, golimumab (including biosimilars), and/or
- •After at least 14 weeks dosage (example, at least 4 doses) of infliximab (including biosimilars) Documented IR may include inadequate improvement or loss in response after initial improvement in joint counts or other parameters of disease activity
排除标准
- •Has a confirmed or suspected clinical immunodeficiency syndrome not related to treatment of RA or has a family history of congenital or hereditary immunodeficiency unless confirmed absent
- •Is (anatomically or functionally) asplenic
- •Has experienced myocardial infarction, unstable ischemic heart disease, or stroke less than or equal to (<=) 12 weeks of screening
- •Has a diagnosis of congestive heart failure including medically controlled, asymptomatic congestive heart failure
- •Has a history of known demyelinating disease such as multiple sclerosis or optic neuritis
研究组 & 干预措施
Certolizumab + Nipocalimab
Participants will receive nipocalimab IV and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by nipocalimab IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.
干预措施: Certolizumab (Drug)
Certolizumab + Placebo
Participants will receive placebo intravenously (IV) and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by placebo IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.
干预措施: Placebo (Drug)
Certolizumab + Placebo
Participants will receive placebo intravenously (IV) and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by placebo IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.
干预措施: Certolizumab (Drug)
Certolizumab + Nipocalimab
Participants will receive nipocalimab IV and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by nipocalimab IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22.
干预措施: Nipocalimab (Drug)
结局指标
主要结局
Change From Baseline in Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) at Week 12
时间窗: Baseline (Week 0), Week 12
Change from baseline in DAS28-CRP at Week 12 were reported. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity, and C-reactive protein (CRP; in milligrams per liter \[mg/L\]). The set of 28 joint count was based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. Score on the DAS28 ranged from 0 to 10, where higher scores indicated more disease activity. Negative changes from baseline indicated improvement of arthritis.
次要结局
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) Response 20 at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 70 Response at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 90 Response at Week 12(Week 12)
- Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Remission at Week 12(Week 12)
- Percentage of Participants Who Achieved Disease Activity Index Score 28 Using C-reactive Protein (DAS28-CRP) Low Disease Activity (LDA) at Week 12(Week 12)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12(Baseline (Week 0), Week 12)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12(Baseline (Week 0), Week 12)