A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Proof-of-concept Study Evaluating the Efficacy and Safety of Nipocalimab Administered Intravenously in Participants With Active Rheumatoid Arthritis Despite Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 27
- 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 and safety of nipocalimab versus placebo in participants with moderate to severe active rheumatoid arthritis (RA).
详细描述
RA is a chronic autoimmune inflammatory disorder of unknown etiology that occurs in approximately 1 percent (%) of the population. Nipocalimab (also referred to as JNJ-80202135 and M281) is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable (Fc) receptor (FcRn). Nipocalimab has a unique mechanism of action whereby it blocks the IgG binding site on endogenous FcRn and is expected to decrease pathogenic IgG antibody concentrations. A significant involvement of pathogenic IgG antibodies has been demonstrated in autoimmune diseases including RA. The primary hypothesis is that treatment with nipocalimab intravenously (IV) every 2 weeks (q2w) is superior to placebo in participants with moderate to severe active rheumatoid arthritis (RA) as assessed by the mean change from baseline in the disease activity index score 28 using C-reactive Protein (DAS28-CRP) at Week 12. The study consists of a Screening Period (less than or equal to [<=] 6 Weeks), Double-blind Treatment Period (12 Weeks), and a Safety Follow-up Period (6 Weeks). Key safety assessments will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interests (AESIs), clinical laboratory safety tests (hematology, chemistry, and lipid profile), vital signs, and physical examination. The total duration of the study is up to 24 weeks.
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)/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 swollen and 6 tender joints out of the 66/68-swollen and tender joint count at the time of screening and at baseline
- •Is positive for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) at screening
- •Screening C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram per deciliter (mg/dL) by the central laboratory
- •A woman of childbearing potential must have a negative highly sensitive urine pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine (beta-hCG) pregnancy test at Week 0 prior to administration of study intervention
排除标准
- •Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her RA or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
- •Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 12 weeks before the first administration of study intervention or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first administration of study intervention)
- •Is (anatomically or functionally) asplenic
- •Has experienced myocardial infarction (MI), unstable ischemic heart disease, or stroke within 12 weeks of screening
- •Has other known inflammatory diseases that might confound the evaluations of benefit from nipocalimab therapy, including but not limited to ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, Lyme disease
- •Is currently taking immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics
研究组 & 干预措施
Group 1: Placebo
Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy.
干预措施: Placebo (Other)
Group 2: Nipocalimab
Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy.
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) 20 at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 70 at Week 12(Week 12)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 90 at Week 12(Week 12)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention(From Week 0 up to Week 10)
- 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) European League Against Rheumatism (EULAR) 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)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18))
- Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18))
- Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)(From Week 0 up to 8 weeks post last dose at Week 10 (up to Week 18))