Study design of the phase IV, randomized, placebo-controlled REMOdeling with Dupilumab in Eosinophilic esophagitis Long-term (REMODEL) trial.

Background: Esophageal distensibility, measured by endoluminal functional lumen imaging probe (EndoFLIP), identifies esophageal fibrostenotic changes and is impaired in patients with eosinophilic esophagitis (EoE). Early-phase clinical trials suggested dupilumab could increase esophageal distensibility. However, there are limited data on the long-term impact of dupilumab treatment on fibrostenosis. Objectives: To evaluate the long-term efficacy of dupilumab, including its impact on esophageal fibrostenotic progression, in adult patients with EoE. Design: The phase IV study is comprised of a randomized, double-blind, placebo-controlled trial period for 24 weeks, followed by an open-label extension for 104 weeks. Methods and analysis: In total, 69 adult patients with endoscopically and histologically active EoE have been recruited from 30 global sites and randomized 2:1 to receive dupilumab 300 mg once weekly (qw) or placebo during the double-blind treatment period. Eligible patients continuing into the open-label extension period will receive dupilumab 300 mg qw. The primary endpoint is absolute change from baseline in esophageal distensibility plateau at week (W)24 measured by EndoFLIP. Secondary endpoints include change in esophageal distensibility plateau at W76 and W128; histologic, endoscopic, and molecular features of EoE at W24, W76, and W128; and long-term safety. After the double-blind treatment period, endpoints will be summarized with descriptive statistics. Ethics: REMODEL will be conducted in accordance with the Declaration of Helsinki, the Council for International Organizations of Medical Sciences international ethical guidelines, and the International Council for Harmonisation Good Clinical Practice guidelines. The protocol was approved by an institutional review board before study initiation. Discussion: REMODEL will address whether long-term dupilumab treatment can mitigate fibrostenotic progression in patients with EoE and may provide new insights into the roles of interleukin-4 and -13 in the pathophysiology and progression of EoE. Trial registration: All patients will provide informed consent. REMODEL was registered on ClinicalTrials.gov (NCT06101095) on October 19, 2023.