A Phase IIb Randomized Clinical Study of an Anti-αvβ6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis

Rationale: Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. Objectives: To evaluate the efficacy and safety of BG00011, an anti-avb6 IgG1 monoclonal antibody, in the treatment of patients with IPF. Methods: In a phase IIb randomized, double-blind, placebocontrolled 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) 20.097 L (0.0600) versus 20.056 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.

Automated summary

The efficacy and safety of BG00011, an anti-avb6 IgG1 monoclonal antibody, in the treatment of idiopathic pulmonary fibrosis (IPF) were evaluated in a phase IIb randomized controlled trial. The results showed that there was no significant difference in FVC change from baseline between patients who received BG00011 or placebo at Week 26. However, patients in the BG00011 group showed a worsening trend after Week 26 and serious adverse events occurred more frequently in BG00011 patients, including four deaths. The study suggests that further research is needed to identify new treatment strategies for IPF.