BACKGROUND and DESIGN:ACT001, a parthenolide-derived investigational drug that targets NF-?B and STAT3 signaling pathways, was evaluated in a phase 2 study to treat IPF or fILD patients in Arm 1 (ACT001 alone) or Arm 2 (ACT001 plus SOC) for up to 52 weeks with absolute change from baseline to week 52 in mean FVC% pred values as main end point with 12 weeks as minimal exposure for efficacy analyses.

RERULTS:44 patients (35 IPF, 9 fILD) were enrolled and dosed at least once. The mean age was 70.0 years and 75.0% were men. Mean baseline FVC% pred was 75.3% for this interim analysis performed at week 52 in 40 patients of efficacy population (7 IPF and 4 fILD in Arm 1; 3 fILD and 26 IPF in Arm 2) . Main absolute change in FVC% pred and 6MWD were -0.86 and 3.31 meters respectively (35 out of 40 patients). For 19 IPF patients in Arm 2, mean absolute change in FVC% pred and FVC decline were -2.77 (median -2.0) and -130 ml (median -120ml) whereas mean 6MWD was 11.58 meters (median 12.0) and ratio of non-progression patients was 37%. Similar mean absolute FVC% change (-2.71, median -2.0) was noted in IPF patients in Arm 1 whereas a mean absolute FVC% increase of 0.52 (median 1.0) was noted in 7 fILD patients (from Arm 1 and 2). A total of 240 TEAEs were reported primarily in infection, pulmonary and GI areas. 25 out of 240 TEAEs were likely related to ACT001 and were largely grade 1 or 2 events. No ACT001-realted SAE or study discontinuation was identified.  

CONCLUSIONS: ACT001 treatment resulted in slower decline in pulmonary function tests over 52 weeks. A trend of disease stabilization was noted in about half of patients across several sub-groups of ILD patients. Further studies are warranted in more IPF and fILD patients.