The value of imaging and clinical outcomes in a phase II clinical trial of a lysophosphatidic acid receptor antagonist in idiopathic pulmonary fibrosis.

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease characterized by worsening dyspnea and lung function and has a median survival of 2-3 years. Forced vital capacity (FVC) is the primary endpoint used most commonly in IPF clinical trials as it is the best surrogate for mortality. This study assessed quantitative scores from high-resolution computed tomography (HRCT) developed by machine learning as a secondary efficacy endpoint in a 26-week phase II study of BMS-986020 - an LPA receptor antagonist - in patients with IPF.

METHODS

HRCT scans from 96% (137/142) of randomized subjects were utilized. Quantitative lung fibrosis (QLF) scores were calculated from the HRCT images. QLF improvement was defined as ⩾2% reduction in QLF score from baseline to week 26.

RESULTS

In the placebo arm, 5% of patients demonstrated an improvement in QLF score at week 26 compared with 15% and 27% of patients in the BMS-986020 600 mg once daily (QD) and twice daily (BID) arms, respectively [ placebo:  = 0.08 (600 mg QD);  = 0.0098 (600 mg BID)]. Significant correlations were found between changes in QLF and changes in percent predicted FVC, diffusing capacity for carbon monoxide (DLCO), and shortness of breath at week 26 ( = -0.41,  = -0.22, and  = 0.27, respectively; all  < 0.01).

CONCLUSIONS

This study demonstrated the utility of quantitative HRCT as an efficacy endpoint for IPF in a double-blind, placebo-controlled clinical trial setting.