Division of Pulmonary, Critical Care and Sleep Medicine, Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, Washington.
Biogen Inc., Cambridge, Massachusetts.
Am J Respir Crit Care Med. 2022 Nov 1;206(9):1128-1139. doi: 10.1164/rccm.202112-2824OC.
Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. To evaluate the efficacy and safety of BG00011, an anti-αβ IgG1 monoclonal antibody, in the treatment of patients with IPF. In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. The primary endpoint was FVC change from baseline at Week 52. Because of early trial termination (imbalance in adverse events and lack of clinical benefit), endpoints were evaluated at Week 26 as an exploratory analysis. One hundred six patients were randomized and received at least one dose of BG00011 ( = 54) or placebo ( = 52). At Week 26, there was no significant difference in FVC change from baseline between patients who received BG00011 ( = 20) or placebo ( = 23), least squares mean (SE) -0.097 L (0.0600) versus -0.056 L (0.0593), respectively ( = 0.268). However, after Week 26, patients in the BG00011 group showed a worsening trend. Eight (44.4%) of 18 who received BG00011 and 4 (18.2%) of 22 who received placebo showed worsening of fibrosis on high-resolution computed tomography at the end of treatment. IPF exacerbation/or progression was reported in 13 patients (all in the BG00011 group). Serious adverse events occurred more frequently in BG00011 patients, including four deaths. The results do not support the continued clinical development of BG00011. Further research is warranted to identify new treatment strategies that modify inflammatory and fibrotic pathways in IPF. Clinical trial registered with www.clinicaltrials.gov (NCT03573505).
特发性肺纤维化（IPF）的治疗选择有限。评估 BG00011（一种抗αβ IgG1 单克隆抗体）治疗 IPF 患者的疗效和安全性。在一项 IIb 期随机、双盲、安慰剂对照试验中，IPF 患者（FVC≥50%预测值，有或无背景治疗）按 1:1 随机分为每周一次皮下注射 BG00011 56mg 或安慰剂。主要终点是第 52 周时从基线的 FVC 变化。由于早期试验终止（不良事件不平衡和缺乏临床获益），终点在第 26 周作为探索性分析进行评估。106 名患者被随机分配并至少接受一剂 BG00011（n=54）或安慰剂（n=52）。第 26 周时，接受 BG00011（n=20）或安慰剂（n=23）的患者从基线的 FVC 变化无显著差异，最小二乘均值（SE）分别为-0.097L（0.0600）和-0.056L（0.0593）（n=0.268）。然而，第 26 周后，BG00011 组的患者出现恶化趋势。在治疗结束时，18 名接受 BG00011 的患者中有 8 名（44.4%）和 22 名接受安慰剂的患者中有 4 名（18.2%）出现纤维化加重，高分辨率计算机断层扫描显示纤维化加重。13 名患者（均在 BG00011 组）报告了 IPF 恶化/进展。BG00011 患者更频繁地发生严重不良事件，包括 4 例死亡。结果不支持继续开发 BG00011。需要进一步研究以确定新的治疗策略，这些策略可以改变 IPF 中的炎症和纤维化途径。临床试验在 www.clinicaltrials.gov 注册（NCT03573505）。
