TY - JOUR T1 - Late Breaking Abstract - Evaluation of the JNK inhibitor, CC-90001, in a phase 1b pulmonary fibrosis trial JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/1393003.congress-2017.OA474 VL - 50 IS - suppl 61 SP - OA474 AU - Steven Greenberg AU - Gerald Horan AU - Brydon Bennett AU - Kate Blease AU - Ying Ye AU - Ada Azaryan AU - Francisco Ramirez-Valle AU - Ralph Ceres AU - Peter Schafer Y1 - 2017/09/01 UR - http://erj.ersjournals.com/content/50/suppl_61/OA474.abstract N2 - Aims/Objectives: Although recently approved treatments for IPF delay lung function decline, novel therapeutic options are needed. c-Jun N-terminal kinase (JNK), a stress-activated protein kinase, has been implicated in pulmonary fibrosis (PF) (Alcorn, 2009). In a previous study, CC-930, a first generation JNK inhibitor with a JNK2 bias, maintained stable FVC in subjects with IPF treated for 6 mos and decreased serum disease biomarkers (van der Velden, 2016). A study using mouse knockouts suggest JNK1, rather than JNK2, is the key JNK isoform in mediating PF (Alcorn, 2009).Methods: CC-90001 is a selective JNK inhibitor 12.9-fold more potent for JNK1 inhibition than JNK2 in a cell-based model. In a phase 1b study in patients with PF, CC-90001 (100mg QD, 200mg QD and 400mg QD) was continuously administered over 12 wks.Results: 16 subjects with PF (15 IPF; 1 RA-ILD) were treated with CC-90001, 100mg (n=3), 200mg (n=7) or 400mg (n=6). Fifteen subjects completed 12 wks of treatment. The most common AEs were GI in nature (all mild to moderate). Two of 3 subjects in the 100mg group had FVC declines at week 12 whereas 10 of 12 (83%) subjects in the combined 200/400mg groups had positive FVC changes at week 12. Mean FVC change from baseline in the combined 200/400mg groups was +168 ml (95% CI: +71 to +276). Plasma tenascin-C levels were reduced from a mean 717 at baseline to 585 ng/ml at week 12 (-132 ng/ml, 95% CI: -212 to -51).Conclusions: CC-90001 was associated with an overall lack of FVC decline in the 200/400mg dose groups, trends in reduced tenascin-C, and acceptable safety over 12 wks of treatment in patients with PF. These data support further clinical development of CC-90001 in patients with IPF. ER -