Design of a phase 3, randomized, double-blind, placebo-controlled, 48-week study to evaluate the efficacy and safety of cendakimab in adult and adolescent patients with eosinophilic esophagitis

Background

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory condition that interferes with normal food ingestion, negatively impacting quality of life (QoL). Treatment options include proton pump inhibitors, corticosteroids, biologics, or dietary elimination; however, ∼1/3 of patients remain insufficiently controlled. The pathogenesis of EoE involves interleukin-13 (IL-13); therefore, targeted IL-13 inhibition may be beneficial. In a phase 2 study, cendakimab, a recombinant, humanized anti–IL-13 monoclonal antibody, significantly reduced mean esophageal eosinophil counts and improved other inflammatory parameters in patients with EoE. These findings prompted further investigation of the efficacy and safety of cendakimab in adults and adolescents with EoE in a phase 3 registrational study (NCT04753697), the design of which is presented here.

Methods

This multicenter, multinational, randomized, double-blind, placebo-controlled, 48-week, treat-through study plans to enroll 399 adults and adolescents. Randomized patients (1:1:1) will receive subcutaneous administration of 1) cendakimab 360 mg once weekly (QW) for 48 weeks, 2) cendakimab 360 mg QW for 24 weeks followed by cendakimab 360 mg every other week (with matching placebo on alternative weeks to maintain the blind) for 24 weeks, or 3) placebo QW for 48 weeks. Co-primary endpoints are mean change from baseline in dysphagia days and proportion of patients with eosinophil histologic response, defined as peak esophageal eosinophil count ≤6 per high-power field, at 24 weeks. Secondary and exploratory endpoints will address endoscopic and histologic features, QoL, safety, and pharmacokinetic assessments.

Conclusion

This phase 3 pivotal study will determine whether cendakimab provides an effective, safe, targeted treatment for patients with EoE.