Late Breaking Abstract - Synthetic Arm Generation Utilizing Real-World Patient Data Demonstrates Treatment Effect in the Phase 2a AIR trial of Buloxibutid in IPF

<bold>Objectives:</bold> To generate a synthetic control arm (SCA) for efficacy testing of buloxibutid in idiopathic pulmonary fibrosis (IPF). <bold>Methods:</bold> AIR was an open-label, phase 2a trial of oral buloxibutid 100 mg BID for up to 36 weeks in treatment-naïve IPF patients. For SCA, 20,000 control arms (using real world data from the Qureight platform) were generated by Monte Carlo Cross Validation (MCCV). Matching similarity was assessed using chi-squared, t-, and kernel tests. Matching was on age, sex, FVC%, DLCO%, and FEV1%. 408 randomly sampled groups of 48 patients were created. Discontinuations from the treatment arm were imputed according to the mean SCA decline. <bold>Results:</bold> SCAs were well matched with the treatment arm (p=0.23). SCAs generated reference distributions of mean FVC (mL) change (Fig 1A). Mean change in FVC for the treatment group after 36 weeks was 23.2ml (SD=508.2, N=48) vs. -114.8ml (SD=45.2) across 408 SCAs (Fig 1B). The right-tailed test for treatment effect (a=0.05) based on this distribution yielded p-value of 0.0025 or expressed alternatively, 99.75% of SCAs had mean FVC change less than the AIR cohort. <bold>Conclusions:</bold> We have demonstrated a statistically significant treatment effect for 100mg BID of buloxibutid at 36 weeks, utilizing MCCV-generated synthetic control arms with matched clinical variables. This is the first use of synthetically generated control arms for efficacy testing in IPF. <fig><object-id>erj;66/suppl_69/PA3043/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>