An Open-label Randomized Phase 1 Study to Investigate the Pharmacokinetics and Pharmacodynamics of Subcutaneous and Intravenous Administrations of Golimumab to Subjects With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 主要终点
- Pharmacokinetics (PK) (Cmax, AUClast, AUCinf, t1/2, systemic clearance, and volume of distribution) following IV administration
研究概览
简要总结
This is a Phase 1, pharmacokinetic and pharmacodynamic study of intravenous and subcutaneous administered golimumab in patients with rheumatoid arthritis.
详细描述
A Phase 1, randomized (study drug route of administration assigned by chance), open label (both physician and patient know that golimumab has been assigned), study of golimumab in patients with rheumatoid arthritis (RA). The purpose of this study is to compare the pharmacokinetic (how the body effects the drug) and pharmacodynamic (how the drug effects the body) effects of golimumab administered through a vein in the arm or by injection under the skin. Safety assessments will be performed throughout the study and include obtaining and evaluating laboratory tests, vital signs (eg, blood pressure), and the occurrence and severity of adverse events. The study will also assess the clinical effects of golimumab on RA. The study is planned for approximately 45 patients, which are randomized at a 2:1 ratio to receive golimumab SC or IV. Male or female patients who have been diagnosed with RA for at least 3 months and who are 18 years of age or older may be able to participate. Subcutaneous (SC) injections of 100 mg golimumab every 4 weeks through Week 20 or intravenous (IV) administrations of 2 mg/kg golimumab on Days 1 and 85.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of RA for at least 3 months prior to screening
- •Have no history of latent or active tuberculosis (TB) and test negative for TB
排除标准
- •Have inflammatory diseases other than RA
- •Have been treated with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives other than methotrexate (MTX), sulfasalazine, or hydroxychloroquine during the 4 weeks prior to the first administration of study agent
- •Have received intramuscular (IM), IV, or intra-articular corticosteroids within 4 weeks of study agent administration
- •Have a known hypersensitivity to human Ig proteins
- •Have received infliximab, golimumab, adalimumab or abatacept within 3 months, or etanercept or anakinra within 1 month prior to the first administration of study agent
- •Have received alefacept, efalizumab, natalizumab, rituximab, or any B-cell-depleting agent
- •Have been treated with any other biologics or investigational drugs, within 5 half-lives of that drug prior to the first administration of study agent
- •Have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis, prior to screening
- •Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening
- •Have had a serious infection (eg, hepatitis, pneumonia, pyelonephritis, or sepsis)
研究组 & 干预措施
001
Golimumab IV infusions of 2 mg/kg golimumab on Days 1 and 85.
干预措施: Golimumab (Drug)
002
Golimumab SC injection of 100 mg every 4 weeks through Week 20
干预措施: Golimumab (Drug)
结局指标
主要结局
Pharmacokinetics (PK) (Cmax, AUClast, AUCinf, t1/2, systemic clearance, and volume of distribution) following IV administration
时间窗: 169 days
Plasma concentrations of golimumab following SC administration
时间窗: 211 days
Pharmacokinetics (PK) [Cmax, tmax, AUC (0-4wk), t1/2 for last dose only, R[AUC(0-4wk)] following SC administration
时间窗: 211 days
Plasma concentrations of golimumab following IV administration
时间窗: 169 days
次要结局
- Pharmacodynamics (PD), including C-reactive protein, IL 6, serum amyloid A, tumor necrosis factor alpha, IL 18, E selectin, vascular endothelial growth factor, matrix metalloproteinases, leptin, and haptoglobin(up to 211 days)
- The number and severity of adverse events(up to 211 days)
- Efficacy as assessed by percent change in the American College of Rheumatology (ACR) score(up to 169 days)
- ACR (American College of Rheumatology) scores(up to 169 days)