A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee.
A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee.
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DOI：
10.1186/ar3430
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发表时间：
2011-07-29
影响因子：
4.9
通讯作者：
Zack DJ
中科院分区：
文献类型：
--
作者：
Cohen SB;Proudman S;Kivitz AJ;Burch FX;Donohue JP;Burstein D;Sun YN;Banfield C;Vincent MS;Ni L;Zack DJ
AMG 108是一种完全人类的免疫球蛋白亚类G2（IgG2）单克隆抗体，它结合了人白细胞介素-1（IL-1）受体1型，抑制IL-1A和IL-1B的活性。在临床前研究中，IL-1抑制作用在骨关节炎（OA）模型中被证明是有益的。这项两部分研究的目的是评估AMG 108的安全性和药代动力学（PK； A部分）和临床效应（B部分）在双盲，安慰剂控制的，多剂量的多剂量研究中膝盖。
在A部分中，患者皮下接受安慰剂或AMG 108（SC; 75 mg或300 mg）或静脉内（IV; 100 mg或300 mg），每4周一次，持续12周；在B部分中，患者接受安慰剂或300 mg AMG 108 SC，每4周一次，持续12周。 AMG 108的临床效应是在B部分中通过使用西部Ontario和McMaster大学（WOMAC）骨关节炎指数疼痛评分来测量的。
在A部分中，有68名患者被随机分配，64例接受了研究产品。在B部分中，随机分配了160名患者，159例接受了研究产品。 AMG 108的耐受性很好。大多数不良事件（AES），感染性AE，严重的AE和感染以及由于AES而退出研究的大多数不良事件，在活跃组和安慰剂组中都以类似的速度发生。据报道，一名80岁的患者（A部分，300 mg IV AMG 108；由于Lobar肺炎并发症）。 AMG 108血清浓度时间曲线表现出非线性PK。与安慰剂组相比，B部分中的AMG 108组在统计学上微不足道但在数值上的疼痛改善更大，如WOMAC疼痛评分所示（中位数变化，分别为-63.0对-37.0）。
膝盖OA患者的AMG 108 SC和IV的安全性与安慰剂相当。接受AMG 108的患者在统计学上显得微不足道但在数值上疼痛的改善改善。但是，观察到临床益处的最小（如果有的话）。
这项研究已在ClinicalTrials.gov中注册，并带有标识符NCT00110942。
AMG 108 is a fully human, immunoglobulin subclass G2 (IgG2) monoclonal antibody that binds the human interleukin-1 (IL-1) receptor type 1, inhibiting the activity of IL-1a and IL-1b. In preclinical studies, IL-1 inhibition was shown to be beneficial in models of osteoarthritis (OA). The purpose of this two-part study was to evaluate the safety and pharmacokinetics (PK; Part A) and clinical effect (Part B) of AMG 108 in a double-blind, placebo-controlled, multiple-dose study in patients with OA of the knee. In Part A, patients received placebo or AMG 108 subcutaneously (SC; 75 mg or 300 mg) or intravenously (IV; 100 mg or 300 mg) once every 4 weeks for 12 weeks; in Part B, patients received placebo or 300 mg AMG 108 SC, once every 4 weeks for 12 weeks. The clinical effect of AMG 108 was measured in Part B by using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index pain score. In Part A, 68 patients were randomized, and 64 received investigational product. In Part B, 160 patients were randomized, and 159 received investigational product. AMG 108 was well tolerated. Most adverse events (AEs), infectious AEs, serious AEs and infections, as well as withdrawals from the study due to AEs occurred at similar rates in both active and placebo groups. One death was reported in an 80-year-old patient (Part A, 300 mg IV AMG 108; due to complications of lobar pneumonia). AMG 108 serum concentration-time profiles exhibited nonlinear PK. The AMG 108 group in Part B had statistically insignificant but numerically greater improvement in pain compared with the placebo group, as shown by the WOMAC pain scores (median change, -63.0 versus -37.0, respectively). The safety profile of AMG 108 SC and IV was comparable with placebo in patients with OA of the knee. Patients who received AMG 108 showed statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed. This study is registered with ClinicalTrials.gov with the identifier NCT00110942.
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6
作者：
Fernandes, J;Tardif, G;Pelletier, JP
通讯作者：
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影响因子：
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de Crombrugghe, B