Mirna Chehade1, Evan S. Dellon2, Jonathan M. Spergel3, Marc E. Rothenberg4, Bin Yao5, Leda P. Mannent6, Elizabeth Laws7, Kiran Patel7, Bethany Beazley5
1Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2University of North Carolina School of Medicine, Chapel Hill, NC, USA; 3Children's Hospital of Philadelphia, Philadelphia, PA, USA; 4Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA; 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 6Sanofi, Chilly-Mazarin, France; 7Sanofi, Bridgewater, NJ, USA
Objectives: Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of the esophagus that substantially impairs quality of life. Incidence and prevalence of EoE in young children are increasing. Current treatment options lack specificity, present adherence challenges, or may offer suboptimal disease control. Dupilumab, a fully human VelocImmune®-derived monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. In the 3-part phase 3 LIBERTY EoE TREET study, weekly dupilumab 300 mg versus placebo demonstrated significant and clinically meaningful improvements in histologic, symptomatic, endoscopic, and transcriptomic measures of EoE, and was well tolerated in patients aged ≥ 12 years. The Phase 3 EoE KIDS study (NCT04394351) is designed to evaluate the efficacy, safety, and tolerability of dupilumab versus placebo in pediatric patients, aged 1–11 years, with active EoE unresponsive to proton pump inhibitors (PPI).
Methods: This study consists of 2 parts. In Part A, 102 participants were randomized 1:1:1 to a subcutaneous dupilumab high-exposure dose, dupilumab low-exposure dose, and matching placebo for a 16-week double-blind treatment period. In Part B, all participants from Part A will be offered to receive a subcutaneous dupilumab high- or low-exposure dose for a 36-week extended treatment period. Key inclusion criteria include: age 1–11 years; documented diagnosis of EoE unresponsive to ≥ 8-week PPI; and baseline esophageal intraepithelial eosinophil count of ≥ 15 per high-power field (eos/hpf) in ≥ 2 of 3 regions. Key exclusion criteria include: body weight < 5 kg or ≥ 60 kg at screening, eosinophilic gastroenteritis, and non-EoE causes of esophageal eosinophilia.
Results: The primary endpoint is the proportion of patients achieving a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 16. Secondary efficacy endpoints include: the proportion of patients achieving peak esophageal intraepithelial eosinophil counts of ≤ 6 eos/hpf at Week 52 and < 15 eos/hpf at Weeks 16 and 52; percent change in peak esophageal intraepithelial eosinophil count at Weeks 16 and 52; absolute change in EoE Histologic Scoring System, EoE Endoscopic Reference Score, and type 2 inflammation transcriptional signature score at Weeks 16 and 52; change in the proportion of days with ≥ 1 EoE signs or symptoms and the proportion of total segments within a day with ≥ 1 or more EoE signs or symptoms, as measured by the Pediatric EoE Sign/Symptom Questionnaire (both caregiver and patient versions), at Weeks 16 and 52; change in total Pediatric Eosinophilic Esophagitis Symptom Scores (PEESSv2.0-caregiver version) at Week 16; normalized enrichment scores for the relative change in EoE diagnostic panel and type 2 inflammation transcriptome signatures at Weeks 16 and 52. Secondary safety endpoints include: incidence of treatment-emergent adverse events, serious adverse events, adverse events of special interest, adverse events leading to discontinuation of study drug, and anti-drug antibody responses and titer during the 16-week double-blind treatment period and 36-week extended treatment period. The clinical pharmacology endpoint is concentration of functional dupilumab in serum during the 16-week double-blind treatment period and 36-week extended treatment period.
Conclusions: This ongoing (enrollment is complete) phase 3 trial will comprehensively evaluate the efficacy and safety of dupilumab versus placebo in pediatric patients aged 1–11 years with active eosinophilic esophagitis based on histologic, endoscopic, and molecular outcomes.
Reference: PAGE 30 (2022) Abstr 10173 [www.page-meeting.org/?abstract=10173]
Poster: Methodology - Study Design