P4186A - An Adaptive Phase 2/3 Study Design to Investigate the Efficacy and Safety of Dupilumab Therapy Compared With Placebo in Adults and Adolescents With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis

Evan S. Dellon, MD, MPH¹, Marc E. Rothenberg, MD, PhD², Mirna Chehade, MD, MPH³, Eric Mortensen, MD, PhD⁴, Elizabeth Laws, PhD⁵, Jennifer Maloney, MD⁴, Renata Martincova, MD⁵, Heather Paleczny, MD, PhD⁴, Lila Glotfelty, MD, PhD⁵, Arsalan Shabbir, MD, PhD^4
1University of North Carolina School of Medicine, Chapel Hill, NC; ²Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH; ³Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁵Sanofi, Bridgewater, NJ

Introduction: Eosinophilic gastritis (EoG) and eosinophilic duodenitis (EoD) are chronic inflammatory diseases characterized by pathologic levels of eosinophils (eos) in the stomach and duodenum, respectively. Common symptoms include abdominal pain, nausea, vomiting, early satiety, and weight loss; patients may progress to severe malabsorption and malnutrition. Evidence suggests that type 2 cell cytokines (IL-4, IL-5, and IL-13) play a role in EoG pathogenesis. Currently, there are no approved therapies for EoG. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation in multiple diseases, including eosinophilic esophagitis. Herein, we present the phase 2/3 ENGAGE (NCT05831176) study design which will investigate the efficacy and safety of dupilumab vs placebo in adult and adolescent patients with EoG with or without EoD.

Methods: This study will randomize patients 1:1 to receive dupilumab or placebo (Part A, phase 2), and 1:1:1 to receive one of two possible dupilumab doses, or placebo (Part B, phase 3). Following this will be a 28-week extension period (Part C) where patients who complete Parts A and B will receive active treatment (but dosing regimen will be masked) (Figure). Key inclusion criteria include age ≥12 years, documented diagnosis of EoG by biopsy (≥3 months prior to screening), and history of ≥2 episodes of EoG symptoms per week. Key exclusion criteria include body weight < 40 kg, esophageal stricture unable to be passed with standard upper endoscope or esophageal stricture that requires dilation, Crohn’s disease, eosinophilic colitis, ulcerative colitis, celiac disease, or prior gastric or duodenal surgery.

Results: Primary endpoints will include proportion of patients achieving peak gastric eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) at Week 24 (Parts A and B) and absolute change in the EoG/EoD Symptom Questionnaire Total Symptom Score from baseline to Week 24 (Part B). Secondary endpoints will include proportion of patients achieving both peak gastric and duodenal eos of ≤6 eos/hpf and ≤15 eos/hpf, respectively at Week 24 and Week 52, and incidence of adverse events up to Week 52 (Table).

Discussion: The phase 2/3 ENGAGE study will determine the efficacy and safety of dupilumab in adult and adolescent patients with EoG with or without EoD, to address the urgent need for safe and effective therapies for this disease.



Disclosures:


Evan S. Dellon, MD, MPH¹, Marc E. Rothenberg, MD, PhD², Mirna Chehade, MD, MPH³, Eric Mortensen, MD, PhD⁴, Elizabeth Laws, PhD⁵, Jennifer Maloney, MD⁴, Renata Martincova, MD⁵, Heather Paleczny, MD, PhD⁴, Lila Glotfelty, MD, PhD⁵, Arsalan Shabbir, MD, PhD⁴. P4186A - An Adaptive Phase 2/3 Study Design to Investigate the Efficacy and Safety of Dupilumab Therapy Compared With Placebo in Adults and Adolescents With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.