A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ANTI-INTERLEUKIN-13 MONOCLONAL ANTIBODY RPC4046 IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS

Abstract

Introduction Interleukin-13 (IL-13) has been implicated in the pathogenesis of eosinophilic esophagitis (EoE). RPC4046 prevents binding of IL-13 to IL-13Rα1 and IL-13Rα2 receptors. This study evaluated efficacy and safety of 2 dose levels of RPC4046 compared to placebo (PBO). Methods Subjects were randomized 1:1:1 to receive RPC4046 180 mg [LD] (n=31), RPC4046 360 mg [HD] (n=34), or PBO (n=34). An IV dose on Day 1 was followed by weekly subcutaneous doses. Centrally read esophageal biopsies were obtained at baseline (BL) and Wk16 to assess change in mean eosinophil count (cells/hpf), the primary endpoint. Secondary endpoints included a Daily Symptom Diary (DSD) and EoE Endoscopic Reference Score (EREFS). Safety also was assessed. Results 90 subjects completed the 16-week double-blind period. Mean esophageal eosinophil counts were significantly reduced from BL for both RPC4046 dose levels compared to PBO (mean change: PBO –4.4, LD –94.8, and HD –99.9 [both pAdverse events in >5% of subjects were headache (PBO 14.7%, LD 16.1%, HD 20.6%), upper respiratory tract infection (PBO 8.8%, LD 16.1%, HD 14.7%), and arthralgia (PBO 0%, LD 12.9%, HD 5.9%). Conclusions RPC4046 demonstrated significant reductions in eosinophilic esophagitis and improvements in endoscopic features at both doses, with greater symptom improvement in subjects receiving HD. The Phase 2 data support further study of RPC4046 for EoE.