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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 (forced vital capacity [FVC] ≥50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. Primary endpoint was FVC change from baseline at Week 52. Due to early trial termination (imbalance in adverse events [AEs] and lack of clinical benefit), endpoints were evaluated at Week 26 as an exploratory analysis. MEASUREMENTS AND MAIN RESULTS 106 patients were randomized and received ≥1 dose of BG00011 (n = 54) or placebo (n = 52). At Week 26, there was no significant difference in FVC change from baseline (SE) between patients who received BG00011 (n = 20) or placebo (n = 23), -0.056 L (0.0593) vs. -0.097 L (0.0600), respectively; P=0.268. However, after Week 26, patients in the BG00011 group showed a worsening trend. Eight of 18 (44.4%) who received BG00011 and 4 of 22 (18.2%) who received placebo showed worsening of fibrosis on high-resolution computed tomography at end of treatment. IPF exacerbation/or progression was reported in 13 patients (all in the BG00011 group). Serious AEs 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 registration available at www. CLINICALTRIALS gov, ID: NCT03573505.