A Randomized, Double Blind Placebo Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of AMG 570 in Subjects With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 34
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events
研究概览
简要总结
A study to evaluate safety and tolerability and characterize the pharmacokinetic (PK) profile of rozibafusp alfa following multiple dose administration in adults with rheumatoid arthritis (RA).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body Mass Index: 18-35 kg/m^2
- •Diagnosed with RA (disease duration of at least 6 months)
- •Stable dose of methotrexate (5-25 mg weekly for ≥ 4 weeks)
- •Immunizations up to date
- •Willing to use highly effective contraception during treatment and through end-of-study
排除标准
- •Uncontrolled, clinically significant systemic disease other than RA (i.e., diabetes mellitus, liver disease, asthma, cardiovascular disease, hypertension)
- •Malignancy within 5 years
- •Presence of serious infection, recurrent/chronic infections
- •Class IV RA according to American College of Rheumatology/ (ACR) revised response criteria
- •Diagnosed with Felty's syndrome
- •Known or suspected sensitivity to mammalian cell-derived products
- •History of alcohol and/or substance abuse within the last 12 months
- •Receipt of rituximab at any time in the past
- •Evidence of renal disease
研究组 & 干预措施
Rozibafusp Alfa
Participants will receive rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses). Rozibafusp alfa doses will range from 70 to 420 mg.
Escalation to a higher dose cohort will be contingent on a review indicating that the previous dose regimen has been found to demonstrate an acceptable safety and tolerability profile at a dose level review meeting (DLRM).
干预措施: Rozibafusp Alfa (Drug)
Placebo
Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses).
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events
时间窗: From first dose of study drug to 24 weeks after last dose (up to 34 weeks).
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and clinically significant changes in laboratory test results and physical exam findings. The event does not necessarily have a causal relationship with study treatment. AEs were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe or medically significant, Grade 4 = Life-threatening, and Grade 5 = Death. A serious adverse event is defined as an AE that met at least 1 of the following serious criteria: * fatal; * life threatening; * required in patient hospitalization or prolongation of existing hospitalization; * resulted in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. The investigator assessed whether each AE was related to study drug.
次要结局
- Accumulation Ratio of Cmax(Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose)
- Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa(Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.)
- Terminal Half-life of Rozibafusp Alfa(Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.)
- Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa(Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose.)
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa(Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.)
- Accumulation Ratio of AUCtau(Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose)
- Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa(Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.)