医学
安慰剂
特发性肺纤维化
临床终点
内科学
恶化
不利影响
胃肠病学
随机对照试验
临床试验
外科
肺
病理
替代医学
作者
Ganesh Raghu,Majd Mouded,Daniel C. Chambers,Fernando J. Martínez,Luca Richeldi,Lisa Lancaster,Mark J. Hamblin,Kevin F. Gibson,Iván O. Rosas,Antje Prasse,Guolin Zhao,Michael Serenko,Natasha Novikov,Amy McCurley,Prashant N. Bansal,Christopher Stebbins,Million Arefayene,Stella Ibebunjo,Shelia M. Violette,Diana Gallagher,Jürgen Behr
标识
DOI:10.1164/rccm.202112-2824oc
摘要
Rationale: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To evaluate the efficacy and safety of BG00011, an anti-αvβ6 IgG1 monoclonal antibody, in the treatment of patients with IPF. Methods: 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. Measurements and Main Results: One hundred six patients were randomized and received at least one dose of BG00011 (n = 54) or placebo (n = 52). At Week 26, there was no significant difference in FVC change from baseline between patients who received BG00011 (n = 20) or placebo (n = 23), least squares mean (SE) −0.097 L (0.0600) versus −0.056 L (0.0593), respectively (P = 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. Conclusions: 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).
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