A Phase 2, 2-Part, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Gastritis with or without Eosinophilic Duodenitis

The primary objective of this study is to evaluate the **efficacy** of dupilumab compared with placebo in adult and adolescent patients with **Eosinophilic Gastritis** (EoG), with or without **Eosinophilic Duodenitis** (EoD). This will be assessed through histological measures after 24 weeks of treatment in Part A, and both histological and clinical measures in Part B. Additionally, Part C aims to assess the safety and efficacy of dupilumab over a period of up to 52 weeks. The clinical relevance of this objective lies in determining the potential of dupilumab as a therapeutic option for managing EoG, a condition characterized by inflammation and eosinophil infiltration in the gastrointestinal tract, which can significantly impact patient quality of life.

Secondary objectives include:

• Determining the treatment effect of dupilumab compared with placebo after 24 weeks, assessed by clinical measures in Part A.
• Evaluating the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks.
• Characterizing the trough concentrations of functional dupilumab over time following administration.
• Evaluating the effects of dupilumab on transcriptomic signatures associated with EoG and type 2 inflammation.

The clinical trial involves a total of **252 participants** diagnosed with **Eosinophilic gastritis** (EoG), with or without eosinophilic duodenitis (EoD). The study population includes both male and female subjects aged 12 years and older, encompassing adolescents and adults. Participants were selected based on documented endoscopic biopsy confirming a pathologic diagnosis of EoG at least three months prior to screening. The trial does not include a vulnerable population. Participants are required to have a history of at least two episodes of EoG symptoms per week in the eight weeks before screening and must have completed specific eDiary data entries prior to the baseline visit. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a consistent and documented history of the condition, allowing for a focused assessment of the treatment's efficacy and safety. The trial aims to evaluate the effects of dupilumab compared to placebo over a treatment period of up to 52 weeks.

The clinical trial is designed to evaluate the **efficacy** and safety of **dupilumab** in adult and adolescent patients diagnosed with **eosinophilic gastritis**, with or without **eosinophilic duodenitis**. This is a Phase 2/3 randomized, double-blind, placebo-controlled study, structured into three parts: Part A, Part B, and Part C. The trial aims to assess the treatment effect of dupilumab compared to placebo over a period of up to 52 weeks, with primary and secondary endpoints focusing on histological and clinical measures.

Participants will be randomly assigned to receive either dupilumab or a placebo, administered via subcutaneous injection. The trial will commence with a screening visit to confirm eligibility based on inclusion criteria, such as age (≥12 years), documented endoscopic biopsy, and symptom history. The trial will include multiple study visits, including baseline, follow-up visits at regular intervals, and an end-of-study visit to evaluate the primary and secondary endpoints. The primary endpoints for Parts A and B include the proportion of participants achieving a peak gastric eosinophil count of ≤6 eosinophils per high power field (eos/hpf) and changes in the Eosinophilic Gastritis/Eosinophilic Duodenitis Symptom Questionnaire (EoG/EoD-SQ) Total Symptom Score (TSS).

The expected duration of participant involvement is up to 52 weeks, with the possibility of early termination if certain conditions arise, such as the occurrence of treatment-emergent adverse events (TEAEs) leading to permanent discontinuation of the study treatment. The trial is anticipated to conclude by August 2027, with recruitment starting in October 2023. Participants will be monitored for safety and efficacy throughout the study, with assessments including histological evaluations and symptom questionnaires. The trial will also measure the incidence of treatment-emergent serious adverse events (SAEs) and the presence of anti-drug antibodies (ADA) to dupilumab.

The clinical trial involves the administration of **Dupixent** (dupilumab), a **solution for injection** in a pre-filled syringe. Dupilumab is a monoclonal antibody classified under the ATC code D11AH05. It is administered via **subcutaneous injection**. The dosage regimen for Dupixent is 300 mg per injection, with a maximum daily dose of 300 mg and a total maximum dose of 15,600 mg over the course of the study. The treatment period extends up to 52 weeks. Dupilumab is produced by Sanofi-Aventis Groupe and is identified by the marketing authorization number EU/1/17/1229/002. The primary objective of the trial is to evaluate the efficacy and safety of Dupixent in adult and adolescent patients with **Eosinophilic Gastritis** (EoG), with or without **Eosinophilic Duodenitis** (EoD).

The study also includes a **placebo** treatment, which is designed to match the appearance and administration route of Dupixent. The placebo is administered as a subcutaneous injection, similar to the active treatment, to maintain blinding in the study. The placebo serves as a comparator to assess the treatment effect of Dupixent. The placebo is not associated with any active pharmaceutical ingredient and is used to evaluate the efficacy and safety of the experimental treatment by providing a baseline for comparison.

The efficacy of dupilumab in the treatment of **Eosinophilic Gastritis** (EoG), with or without **Eosinophilic Duodenitis** (EoD), will be assessed through a series of primary and secondary endpoints over the course of a Phase 2/3 clinical trial. The primary endpoints for Parts A and B include the proportion of participants achieving a peak gastric eosinophil count of ≤6 eosinophils per high power field (eos/hpf) and the absolute change in the Eosinophilic Gastritis/Eosinophilic Duodenitis Symptom Questionnaire (EoG/EoD-SQ) Total Symptom Score (TSS). Secondary endpoints across Parts A, B, and C will evaluate additional histological and clinical measures, such as the proportion of participants achieving both a peak gastric eosinophil count of ≤6 eos/hpf and a peak duodenal eosinophil count of ≤15 eos/hpf, as well as changes in symptom scores and eosinophil counts.

Histological assessments will be conducted to measure eosinophil counts in gastric and duodenal tissues, while clinical efficacy will be evaluated using the EoG/EoD-SQ, which captures patient-reported outcomes related to symptom severity. The trial will also monitor changes in the Normalized Enrichment Scores (NES) for type 2 inflammation transcriptome signatures and the EoG disease transcriptome signature. Efficacy assessments will be performed at various timepoints, including after 24 weeks of treatment for Parts A and B, and up to 52 weeks for Part C. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection and analysis.