A Randomized, Double-blind Study to Compare Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of ABP 798 With Rituximab in Subjects With Moderate to Severe Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 311
- 试验地点
- 1
- 主要终点
- Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose
研究概览
简要总结
This trial is designed to determine what effects the human body has on the investigational medicine, ABP 798, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe RA.
This study will also assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women ≥ 18 and ≤ 80 years old
- •Subjects must be diagnosed with rheumatoid arthritis for at least 6 months before baseline
- •Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline and at least one of the following at screening:
- •erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr
- •serum C-reactive protein (CRP) > 1.0 mg/dL
- •Subjects must be taking methotrexate (MTX) for ≥ 12 consecutive weeks and on a stable dose of MTX 7.5 to 25 mg/week for ≥ 8 weeks prior to receiving the investigational product (IP), and be willing to remain on a stable dose throughout the study
- •Subject has no known history of active tuberculosis
排除标准
- •Class IV RA, Felty's syndrome or history of prosthetic or native joint infection
- •Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome
- •Use of commercially available or investigational biologic therapies for RA as follows:
- •anakinra, etanercept within 1 month prior to first dose of IP
- •infliximab, abatacept, tocilizumab, golimumab, certolizumab within 3 months prior to first dose of IP
- •other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) prior to first dose of IP
- •Previous receipt of rituximab or a biosimilar of rituximab
- •Other Inclusion/Exclusion criteria may apply
研究组 & 干预措施
ABP 798 / ABP 798
Participants received ABP 798 on days 1 and 15 (dose 1) and a second dose of ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.
干预措施: ABP 798 (Drug)
Rituximab (US) / ABP 798
Participants received rituximab (United States [US] formulation) on days 1 and 15 (dose 1) and transitioned to receive ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.
干预措施: ABP 798 (Drug)
Rituximab (US) / ABP 798
Participants received rituximab (United States [US] formulation) on days 1 and 15 (dose 1) and transitioned to receive ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.
干预措施: Rituximab (US) (Drug)
Rituximab (EU) / Rituximab (EU)
Participants received rituximab (European Union [EU] formulation) on days 1 and 15 (dose 1) and a second dose of rituximab (EU formulation) at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.
干预措施: Rituximab (EU) (Drug)
结局指标
主要结局
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose
时间窗: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUCinf was estimated using the linear trapezoidal rule.
Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose
时间窗: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Maximum observed concentration following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.
次要结局
- Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.)
- Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hour postdose, and at days 29, 57, and 85 (week 12).)
- Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.)
- Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)(Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Terminal Elimination Half-life (t1/2)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Terminal Elimination Rate Constant (λz)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57 and 85 (week 12).)
- Clearance (CL)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Mean Residence Time (MRT)(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Percent of AUC Extrapolation (AUC%Extrap)(Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- AUC0-12 wk/AUCinf(Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).)
- Percentage of Participants With an ACR50 Response(Baseline and Weeks 8, 12, 24, 40, and 48)
- Percentage of Participants With an ACR70 Response(Baseline and Weeks 8, 12, 24, 40, and 48)
- Change From Baseline in Disease Activity Score 28-CRP at Week 24(Baseline and Week 24)
- Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48(Baseline and weeks 8, 12, 40, and 48)
- Number of Participants Who Developed Anti-drug Antibodies(Day 1 through the end of study (48 weeks).)
- Duration of Complete Depletion in CD19+ Cell Count(CD19+ cell count was assessed at baseline, days 2, 3, weeks 4, 24, and 48)
- Percentage of Participants With an ACR20 Response(Baseline and Weeks 8, 12, 24, 40, and 48)
- Hybrid ACR(Baseline and weeks 8, 12, 24, 40, and 48)
- Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3(Day 3)
- Number of Participants With Adverse Events After the First Dose(From day 1 until the first infusion of the second dose (week 24))
- Number of Participants With Clinically Significant Laboratory Findings(Day 1 through the end of study (48 weeks).)