Allergy Research Foundation, Los Angeles, CA 90025, USA.
Am J Respir Crit Care Med. 2010 Apr 15;181(8):788-96. doi: 10.1164/rccm.200909-1448OC. Epub 2010 Jan 7.
IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways.
To evaluate efficacy and safety of AMG 317 in patients with moderate to severe asthma.
In this phase 2, randomized, double-blind, placebo-controlled study, patients received weekly subcutaneous injections of placebo or AMG 317 (75-300 mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom score.
Mean ACQ change (SE) was -0.49 (0.09) in placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317 75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively (treatment effect P = 0.25). No statistically significant differences were observed in the secondary endpoints. Numerical decreases in number of and time to exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg. Preplanned analyses by tertile of baseline ACQ revealed that patients with higher baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious adverse events were reported in three patients, each noted as not related to study drug.
AMG 317 did not demonstrate clinical efficacy across the overall group of patients. Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores. AMG 317 was safe and well tolerated in this study population. Clinical trial registered with www.clinicaltrials.gov (NCT 00436670).
IL-4 和 IL-13 具有许多在过敏性气道炎症发展中重要的生物学功能，并且与哮喘的发病机制有关。AMG 317 是一种针对 IL-4Ralpha 的完全人源单克隆抗体，可阻断 IL-4 和 IL-13 途径。
评估 AMG 317 在中重度哮喘患者中的疗效和安全性。
在这项 2 期、随机、双盲、安慰剂对照研究中，患者每周接受一次皮下注射安慰剂或 AMG 317（75-300mg），共 12 周，随后进行 4 周随访期。主要终点是从基线到第 12 周时哮喘控制问卷（ACQ）症状评分的变化。
安慰剂组（n=74）的平均 ACQ 变化（SE）为-0.49（0.09），AMG 317 75mg 组（n=73）、150mg 组（n=73）和 300mg 组（n=74）分别为-0.43（0.11）、-0.58（0.12）和-0.70（0.09）（治疗效果 P=0.25）。次要终点未观察到统计学上的显著差异。接受 AMG 317 150mg 和 300mg 治疗的患者的恶化次数和时间均有数值减少。根据基线 ACQ 的三分位数进行的预先计划分析显示，基线 ACQ 评分较高（≥2.86）的患者更有可能对 AMG 317 有反应。有 3 名患者报告了严重不良事件，均被认为与研究药物无关。
AMG 317 在整个患者组中未显示出临床疗效。在基线 ACQ 较高的患者中，几个结局指标有明显的改善。在该研究人群中，AMG 317 安全且耐受良好。该临床试验已在 www.clinicaltrials.gov 上注册（NCT 00436670）。
