Introduction / Rationale Idiopathic pulmonary fibrosis (IPF) is associated with progressive loss of lung function and a median survival of 3-4 years. While current standard of care (SOC) with the antifibrotic agents pirfenidone or nintedanib slows disease progression, prognosis remains poor. There is an unmet need for novel, well-tolerated agents that reduce lung function decline, improve quality of life, and prolong life expectancy. The autotaxin inhibitor GLPG1690 is undergoing evaluation as a novel therapy for IPF and has demonstrated encouraging results in early clinical trials, warranting further studies. This abstract reports the phase III study design. Methods Two identically-designed, phase III, international, randomised, double-blind, placebo-controlled, parallel-group multicentre studies (ISABELA 1 and 2) were initiated in October 2018. Each study is expected to randomise 750 subjects with IPF in a 1:1:1 way to oral GLPG1690 600 mg, GLPG1690 200 mg, or matching placebo, once-daily, in addition to local SOC, for at least 52 weeks. The primary endpoint is the rate of decline of forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are disease progression (defined as the composite endpoint of first occurrence of ≥10% absolute decline in percent predicted FVC (%FVC) or all-cause mortality at Week 52), time to first respiratory-related hospitalisation until the end of the studies, and change from baseline in the St. George’s Respiratory Questionnaire total score at Week 52. Eligible subjects are aged ≥40 years, with a diagnosis of IPF within the previous 5 years, confirmed by central reading of a chest high-resolution computed tomography (HRCT) and a lung biopsy (if available). Subjects must be on stable local SOC for IPF; and have an FVC ≥45% of predicted, forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, and diffusing capacity of the lung for carbon monoxide (DLCO) corrected for haemoglobin ≥30% of predicted. Conclusion GLPG1690 added to SOC will be assessed for the first time in two identically-designed studies, ISABELA 1 and 2, allowing for data pooling. A wide array of endpoints related to efficacy, safety, tolerability, mortality, quality of life, PK/PD and biomarkers will be assessed. Compared to previous IPF programs, a clinically broader range of subjects will be recruited, as eligibility criteria are less restrictive. A proportion of subjects will remain on study drug for longer than 52 weeks, allowing longer-term efficacy and safety data to be collected. Positive findings may ultimately lead to a much‑needed new treatment option for patients with IPF.