Dupilumab in Eosinophilic Gastritis

Study Overview
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Brief Summary
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40 participants with Eosinophilic Gastritis 12-70 years of age will be randomly assigned with dupilumab or placebo subcutaneous injections every two weeks for a total of 12 weeks. Study subjects who complete the 12-week treatment phase, may continue into an open label extension study, where dupilumab will be administered every two weeks for a total of 24 weeks.

Detailed Description
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This is a phase 2, multi-center, randomized, double-blind, placebo-controlled trial testing the efficacy of dupilumab vs. placebo in EG. Qualifying subjects will be randomized 1:1 to either study drug (dupilumab) or placebo, and will receive 600 mg once followed by 300 mg doses every two weeks of study treatment for a total of 6 injections. After the 6th injection subjects may continue into an open-label treatment phase in which dupilumab will be administered every two weeks for a total of 24 weeks. Approximately 14 sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) will take part in the study. The primary objective of this study is to assess the efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, to reduce eosinophilic inflammation in the gastrointestinal tract of patients with EG.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy of Dupilumab (Anti-IL4a) in Subjects With Eosinophilic Gastritis

Conditions
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Eosinophilic Gastritis, Eosinophilic Gastroenteritis

Intervention / Treatment
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* Drug: Dupilumab (blinded)
* Drug: Placebo (blinded)
* Drug: Dupilumab (open-label)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant and/or parent guardian must be able to understand and provide informed consent and/or assent. Willing and able to comply with study visits and activities Age ≥ 12 and < 71 years at study enrollment Histologically active EG at time of screening, with a peak gastric count of ≥ 30 eos/hpf in at least 5 hpfs in the gastric antrum and/or body. History (by patient report) of moderate to severe EG symptoms Stable medical management of EG. Willing to maintain current dietary regimen throughout the course of the study. Diet must have been stable for 8 weeks prior to baseline endoscopy. If have asthma and/or any other chronic allergic conditions they must be willing to maintain their pretrial medications until the end of study. Medication dose can be increased if there is a deterioration in the condition. Score on Asthma Control Test (ACTTM) ≥ 20 Exclusion Criteria: Inability or unwillingness of a participant to give written informed consent or comply with study protocol. Current active H. pylori infection. Systemic gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease. Known or suspected active colitis in the Principal Investigator's opinion or by biopsy. Hypereosinophilic syndrome. History of cancer Current or recent use of biological agents. Leukocyte count has not returned to the relevant lower limit of normal after discontinuing cell depleting biological agents. Current or recent use of any investigational drug. Current use of systemic steroids with daily dose > 10 mg for any reason or steroid burst for > 3 days within 1 month of screening. Prior exposure to dupilumab. History of anaphylaxis to any biologic therapy. Current pregnancy or breastfeeding. Ocular disorder. Individuals who have required use of a systemic corticosteroid for asthma. Received live vaccine 30 days prior to screening or planning on receiving a live vaccine during the time period that he/she is participating in the study. Any esophageal stricture unable to be passed with a standard, diagnostic upper endoscope. History of bleeding disorders or esophageal varices. Active parasitic infection. History of alcohol or drug abuse within 6 months prior to screening. Participant or his/her immediate family is a member of the investigational team. Planned or anticipated major surgical procedure during the study. Initiation, discontinuation or addition of allergens to subcutaneous immunotherapy (SCIT) within 12 months prior to screening. Treatment with sublingual immunotherapy (SLIT) within 6 months prior to screening. Treatment with oral immunotherapy (OIT) within 6 months prior to screening. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals or antifungals within 2 weeks before the baseline visit Known or suspected immunodeficiency disorder, including human immunodeficiency disorder (HIV). Planned or anticipated use of any prohibited medications and procedures during the study. Initiation, discontinuation or change in the dosage regimen of the following Proton pump inhibitors (PPIs) Leukotriene inhibitors Nasal and/or inhaled corticosteroids Women of childbearing potential who are unwilling to practice highly effective contraception.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to either drug or placebo, followed by an open label extension
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dupilumab<br> | Drug: Dupilumab (blinded)<br>* Subcutaneous injection every two weeks as follows: 600 mg initial dose, and 300 mg subsequent doses for a total of 6 injections.<br>Drug: Dupilumab (open-label)<br>* After completing 6 doses of blinded study drug (dupilumab or placebo), participants can continue into the open-label portion of the study, in which all subjects will receive 12 doses (every 2 weeks for 24 weeks) of dupilumab.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo (blinded)<br>* Placebo is matched to the active drug (dupilumab), and is given in the same manner: a subcutaneous injection every two weeks for a total of 6 injections.<br>Drug: Dupilumab (open-label)<br>* After completing 6 doses of blinded study drug (dupilumab or placebo), participants can continue into the open-label portion of the study, in which all subjects will receive 12 doses (every 2 weeks for 24 weeks) of dupilumab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change of peak eosinophil counts in the stomach | We will determine the Relative change from baseline of the peak eosinophil counts in the 5 most eosinophil dense HPFs in the gastric antrum and/or body between drug vs placebo at 12 weeks will be the primary measurement endpoint. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction of disease remission | We will use the 30 eosinophils/hpf threshold, which is the study inclusion level. Comparison between drug vs placebo at week 12 will be the measurement endpoint. | 12 weeks | 
| Change in histologic score of gastric mucosa | Change in histologic score from pre- to post-treatment with dupilumab or placebo as measured by the Eosinophilic Gastritis Biopsy Evaluation Form. The EG Biopsy Evaluation Form assesses 11 different types of histological features, each one rated from 0-2 (0 = absent, 1 = mild/moderate, 2 = marked), with a maximum score of 22 (most severe) and a minimum score of 0 (normal). | 12 weeks | 
| Changes in endoscopic score before and after treatment with dupilumab | Change in endoscopic score from pre- to post-treatment with dupilumab or placebo as measured by Eosinophilic Gastritis Endoscopic Assessment. The Eosinophilic Gastritis Endoscopy Assessment captures 6 endoscopic features of the stomach, each scored from 0-6, varying by endoscopic feature. The maximum score is 43 (most severe), and the minimum is 0 (normal). | 12 weeks | 
| Changes in clinical symptoms as measured by the Severity of Dyspepsia Assessment tool. | Change in symptoms from pre- to post-treatment with dupilumab or placebo as measured by the Severity of Dyspepsia Assessment (SoDA) tool. The SoDA measures 3 domains: Pain Intensity (scored from 2-47, with 47 being the most severe), Non-pain symptoms (scored from 7-35, with 35 being the most severe), and SoDA satisfaction (scored from 2-23, with 23 being the most satisfied). Each domain is assessed independently; they are not summed or averaged. | 12 weeks | 
| Change in blood eosinophil counts | Change in blood eosinophil count before and after treatment with dupilumab or placebo as measured by CBC with differential. | 12 weeks | 
| Assessment of the value of baseline blood and esophageal biomarkers in predicting responsiveness to dupilumab. | The baseline values of blood biomarkers (primarily cytokine levels) as well as esophageal transcripts will be assessed before and after treatment. We will determine if baseline values correlate with drug responsiveness. | 12 weeks |