P2214 - Design of the Phase 4 REMODEL Study Assessing the Effect of Dupilumab on Esophageal Function and Remodeling in Adult Patients With Active Eosinophilic Esophagitis

Ikuo Hirano, MD, FACG¹, Danen Cunoosamy, PhD², Evan S. Dellon, MD, MPH, FACG³, Arjan Bredenoord, MD⁴, Edoardo Savarino, MD⁵, Mei Zhang, PhD², Bram P. Raphael, MD⁶, Tiffany Pela, PharmD, MPH², Amr Radwan, MA, MBBCh⁶, Juby A. Jacob-Nara, MBBS, MD, MPH, MBA^2
1Kenneth C. Griffin Esophageal Center, Northwestern University Feinberg School of Medicine, Chicago, IL; ²Sanofi, Bridgewater, NJ; ³University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC; ⁴Amsterdam University Medical Center, Amsterdam, Noord-Holland, Netherlands; ⁵University Hospital, Padua, Veneto, Italy; ⁶Regeneron Pharmaceuticals Inc., Tarrytown, NY

Introduction: Without treatment, eosinophilic esophagitis (EoE) may progress to esophageal remodeling and stricture formation. Impedance planimetry using the endoluminal functional lumen imaging probe (EndoFLIP) provides a quantitative assessment of the consequences of esophageal remodeling in EoE that are associated with disease complications, including stricture formation and risk of food impaction. Through simultaneous measurement of esophageal luminal dimensions and pressures during volume-controlled distension, the biomechanical properties of the esophageal wall, i.e., esophageal distensibility and compliance, can be objectively assessed. In a previous proof-of-concept study, dupilumab significantly improved esophageal distensibility compared with placebo in patients with EoE. Herein we present the design of the phase 4 REMODEL study (NCT6101095), which will assess the effect of dupilumab treatment on esophageal function and remodeling in adult patients with active EoE.

Methods: Patients will be randomized 2:1 to receive dupilumab or placebo for 24 weeks, after which all patients will receive 104 weeks of open‑label dupilumab (Figure 1). Inclusion criteria include age ≥18 years, a documented diagnosis of EoE by consensus guidelines, baseline endoscopic biopsies with a demonstration of intraepithelial eosinophilic infiltration on central reading, an average of ≥2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening, and body weight ≥40 kg. Key exclusion criteria include hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), any esophageal stricture unable to be passed with a standard, diagnostic, 9–10 mm upper endoscope, and any critical esophageal stricture requiring dilation at screening.

Results: The primary endpoint will be change from baseline to Week 24 in esophageal distensibility plateau as measured by EndoFLIP. An increase in distensibility plateau indicates an improvement in esophageal function. Main secondary endpoints are shown in Table 1.

Discussion: The phase 4 REMODEL study will evaluate the efficacy of dupilumab on the remodeling consequences of EoE. Novel aspects of this study include the use of esophageal distensibility as a primary endpoint and over 2-year prospective evaluation of the effectiveness of dupilumab in EoE. The results from this study will help inform practitioners’ decision-making regarding the management of fibrostenotic phenotypes of EoE.



Disclosures:


Ikuo Hirano, MD, FACG¹, Danen Cunoosamy, PhD², Evan S. Dellon, MD, MPH, FACG³, Arjan Bredenoord, MD⁴, Edoardo Savarino, MD⁵, Mei Zhang, PhD², Bram P. Raphael, MD⁶, Tiffany Pela, PharmD, MPH², Amr Radwan, MA, MBBCh⁶, Juby A. Jacob-Nara, MBBS, MD, MPH, MBA². P2214 - Design of the Phase 4 REMODEL Study Assessing the Effect of Dupilumab on Esophageal Function and Remodeling in Adult Patients With Active Eosinophilic Esophagitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.