| Autor: |
Raghu G; Division of Pulmonary, Critical Care and Sleep Medicine, Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, Washington., Mouded M; Biogen Inc., Cambridge, Massachusetts., Chambers DC; Queensland Lung Transplant Program, The Prince Charles Hospital, Brisbane, Australia.; School of Medicine, The University of Queensland, Brisbane, Australia., Martinez FJ; Department of Pulmonary Critical Care Medicine, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York., Richeldi L; Fondazione Policlinico A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Rome, Italy., Lancaster LH; Department of Medicine, Vanderbilt University, Nashville, Tennessee., Hamblin MJ; Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, Kansas., Gibson KF; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Rosas IO; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Prasse A; Department of Pneumology, Medical School of Hannover, Hannover, Germany; and., Zhao G; Biogen Inc., Cambridge, Massachusetts., Serenko M; Biogen Inc., Cambridge, Massachusetts., Novikov N; Biogen Inc., Cambridge, Massachusetts., McCurley A; Biogen Inc., Cambridge, Massachusetts., Bansal P; Biogen Inc., Cambridge, Massachusetts., Stebbins C; Biogen Inc., Cambridge, Massachusetts., Arefayene M; Biogen Inc., Cambridge, Massachusetts., Ibebunjo S; Biogen Inc., Cambridge, Massachusetts., Violette SM; Biogen Inc., Cambridge, Massachusetts., Gallagher D; Biogen Inc., Cambridge, Massachusetts., Behr J; Department of Medicine V, University Hospital, LMU Munich, German Center for Lung Research (DZL), Munich, Germany. |
| Abstrakt: |
Rationale: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To evaluate the efficacy and safety of BG00011, an anti-α v β 6 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). |
