S0345 Safety and Efficacy of Long-Term Treatment of EoE With Fluticasone Propionate Orally Disintegrating Tablet (APT-1011): Results From 40 Weeks Treatment in a Phase 2b Randomized Double-Blind Placebo-Controlled Trial

Abstract

INTRODUCTION: APT-1011, a novel fluticasone propionate orally disintegrating tablet, induced histological remission and symptom improvement in adults with eosinophilic esophagitis (EoE) after 12 weeks in a phase 2b study. We aimed to evaluate long-term safety and efficacy of APT-1011 in maintaining remission for 52 weeks. METHODS: The FLUTE trial was a 2-part randomized, double-blind, placebo-controlled, dose-ranging study of APT-1011 vs placebo. Participants from 71 sites in 6 countries (N. America; Europe) were randomized in Part 1 to APT-1011 (1.5 mg HS or BID; 3 mg HS or BID) or placebo for 12 weeks. In Part 2, histological responders (≤6 eos/HPF) at Week 12 continued the same treatment to Week 52, and non-responders were assigned to 3 mg BID to Week 52. Histologic remission was evaluated at Weeks 26 and 52. Additional endpoints included endoscopic activity, symptoms and safety. RESULTS: Of 97 subjects who completed Part 1, 93 entered Part 2. Responder rates in Part 1 were 80% 3 mg BID; 67% 3 mg HS; 86% 1.5 mg BID; 48% 1.5 mg HS and 0% placebo. For APT-1011 responders at Week 12, daily doses of 3 mg and 6 mg resulted in sustained remission rates (64-84%) compared to 1.5 mg daily (30%) (Table 1). Of participants on placebo in Part 1, 80% had histological remission at Week 26 with 67% maintaining remission at Week 52. Of APT-1011 non-responders in Part 1, 26% achieved histological remission with ongoing treatment (3 mg BID) at Week 52 (Table 2). For APT-1011 responders in Part 1, the reduction in the number of dysphagia episodes at Week 12 was maintained or further reduced in Part 2; global EoE symptom scores continued to improve for the 3 mg BID and 3 mg HS groups; endoscopic improvement (EREFs) continued for all APT-1011 groups (Figure 1). The most common adverse events were oral/esophageal candidiasis in 11/93 (12%), the majority with BID dosing (7/11 3 mg BID; 3/11 1.5 mg BID; 1/11 3 mg HS). Two abnormal ACTH tests were reported at Week 52; one associated with 19-nortestosterone use and another with lab draw at the incorrect time. CONCLUSION: APT-1011 is highly efficacious for treatment and maintenance of histologic remission in adults with EoE over 52 weeks. The 3 mg HS dose demonstrated the best benefit/risk balance of efficacy and safety, for both induction and maintenance of remission over 52 weeks, with the added benefit of once daily dosing. In addition, one out of 4 APT-1011 treatment failures in Part 1of this study, responded to continued high dose APT-1011.Table 1.: Maintenance of Histological Response Analysis at Weeks 26 and 52 in Week 12 Responders.Table 2.: Histological Response at Week 26 and Maintenance of Response at Week 52 Analysis in Week 12 Non-responders.Figure 1.: Dysphagia Episodes, Global EoE Symptom Scores and EREF Scores over Time by APT-1011 Dosing Group.