A Randomized, Double-blind, Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 252
- 主要终点
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
研究概览
简要总结
Study in participants with RA who have an inadequate response to methotrexate.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Active RA for least 6 months
- •Current RA defined as ≥ 6 swollen joints (out of 66 joints examined) and ≥ 8 tender/painful joints (out of 68 joints examined) at screening and baseline (swollen and tender/painful joint count must not include distal interphalangeal joints) and at least 1 of the following at screening: Erythrocyte sedimentation rate ≥ 28 mm or C-reactive protein > 15 mg/L
- •At least 1 of the following at screening: Rheumatoid factor positive or Anti-cyclic citrullinated peptide antibody positive
- •Currently taking methotrexate for ≥ 12 weeks and on a stable dose of methotrexate at 15 to 25 mg weekly for ≥ 4 weeks at day -1.
排除标准
- •Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening
- •Class IV RA
- •Felty's syndrome
- •Presence of serious infection
- •Significant concurrent medical conditions
- •Pregnant or breast feeding
- •Significant Laboratory abnormalities
- •Any disease-modifying anti-rheumatic drug (DMARD) other than methotrexate within 28 days
- •Leflunomide or live vaccines within 3 months
- •Previous use of any experimental or commercially available biologic DMARD
研究组 & 干预措施
Placebo
Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Placebo (Drug)
Placebo
Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Methotrexate (Drug)
Placebo
Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: folic acid (Dietary Supplement)
Brodalumab 70 mg
70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Brodalumab (Drug)
Brodalumab 70 mg
70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Methotrexate (Drug)
Brodalumab 70 mg
70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: folic acid (Dietary Supplement)
Brodalumab 140 mg
140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week).
干预措施: Brodalumab (Drug)
Brodalumab 140 mg
140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week).
干预措施: Methotrexate (Drug)
Brodalumab 140 mg
140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week).
干预措施: folic acid (Dietary Supplement)
Brodalumab 210 mg
210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Brodalumab (Drug)
Brodalumab 210 mg
210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: Methotrexate (Drug)
Brodalumab 210 mg
210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week).
干预措施: folic acid (Dietary Supplement)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
时间窗: Baseline, week 12
A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: * 50% improvement in 68 tender joint count; * 50% improvement in 66 swollen joint count; and * 50% improvement in at least 3 of the 5 following parameters: * Patient's assessment of joint pain (measured on a 100 mm visual analog scale \[VAS\]), * Patient's global assessment of disease activity (measured on a 0-10 Likert scale), * Physician's global assessment of disease activity (measured on a 0-10 Likert scale), * Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index \[HAQ-DI\]), * Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.
次要结局
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12(Baseline, Week 12)
- Disease Activity Score 28 (DAS28) at Week 12(Week 12)
- Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation(From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).)
- PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)(Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12(Baseline, week 12)
- Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)(Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose)
- PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)(Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose)