Dupilumab in Eosinophilic Gastritis

Phase 2

Active, not recruiting

• Conditions: Eosinophilic Gastroenteritis; Eosinophilic Gastritis
• Interventions: Drug: Placebo (blinded); Drug: Dupilumab (blinded); Drug: Dupilumab (open-label)

• Registration Number: NCT03678545
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-09-18
• Study First Posted: 2018-09-19
• Study Start: 2021-05-15
• Status Verified: 2023-08
• Primary Completion: 2024-03-04
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-05
• Study Completion: 2024-11-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1. Participant and/or parent guardian must be able to understand and provide informed consent and/or assent.
2. Willing and able to comply with study visits and activities
3. Age ≥ 12 and < 71 years at study enrollment
4. 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.
5. History (by patient report) of moderate to severe EG symptoms
6. Stable medical management of EG.
7. Willing to maintain current dietary regimen throughout the course of the study. Diet must have been stable for 8 weeks prior to baseline endoscopy.
8. 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.
9. Score on Asthma Control Test (ACTTM) ≥ 20

Exclusion Criteria

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
2. Current active H. pylori infection.
3. Systemic gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease.
4. Known or suspected active colitis in the Principal Investigator's opinion or by biopsy.
5. Hypereosinophilic syndrome.
6. History of cancer
7. Current or recent use of biological agents.
8. Leukocyte count has not returned to the relevant lower limit of normal after discontinuing cell depleting biological agents.
9. Current or recent use of any investigational drug.
10. Current use of systemic steroids with daily dose > 10 mg for any reason or steroid burst for > 3 days within 1 month of screening.
11. Prior exposure to dupilumab.
12. History of anaphylaxis to any biologic therapy.
13. Current pregnancy or breastfeeding.
14. Ocular disorder.
15. Individuals who have required use of a systemic corticosteroid for asthma.
16. 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.
17. Any esophageal stricture unable to be passed with a standard, diagnostic upper endoscope.
18. History of bleeding disorders or esophageal varices.
19. Active parasitic infection.
20. History of alcohol or drug abuse within 6 months prior to screening.
21. Participant or his/her immediate family is a member of the investigational team.
22. Planned or anticipated major surgical procedure during the study.
23. Initiation, discontinuation or addition of allergens to subcutaneous immunotherapy (SCIT) within 12 months prior to screening.
24. Treatment with sublingual immunotherapy (SLIT) within 6 months prior to screening.
25. Treatment with oral immunotherapy (OIT) within 6 months prior to screening.
26. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals or antifungals within 2 weeks before the baseline visit
27. Known or suspected immunodeficiency disorder, including human immunodeficiency disorder (HIV).
28. Planned or anticipated use of any prohibited medications and procedures during the study.
29. Initiation, discontinuation or change in the dosage regimen of the following Proton pump inhibitors (PPIs) Leukotriene inhibitors Nasal and/or inhaled corticosteroids
30. Women of childbearing potential who are unwilling to practice highly effective contraception.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo (blinded)	-
Placebo	Dupilumab (open-label)	-
Dupilumab	Dupilumab (open-label)	-
Dupilumab	Dupilumab (blinded)	-

Primary Outcome Measures

Name	Time	Method
Relative change of peak eosinophil counts in the stomach	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Induction of disease remission	12 weeks	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.
Change in histologic score of gastric mucosa	12 weeks	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).
Changes in endoscopic score before and after treatment with dupilumab	12 weeks	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).
Changes in clinical symptoms as measured by the Severity of Dyspepsia Assessment tool.	12 weeks	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.
Change in blood eosinophil counts	12 weeks	Change in blood eosinophil count before and after treatment with dupilumab or placebo as measured by CBC with differential.
Assessment of the value of baseline blood and esophageal biomarkers in predicting responsiveness to dupilumab.	12 weeks	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.

Trial Locations

Locations (12)

Northwestern Medicine Digestive Health Center; 🇺🇸 Chicago, Illinois, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of Colorado Denver and Hospital; 🇺🇸 Aurora, Colorado, United States

Riley Children's Hospital; 🇺🇸 Indianapolis, Indiana, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

University of Utah Hospital; 🇺🇸 Salt Lake City, Utah, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of North Carolina School of Medicine; 🇺🇸 Chapel Hill, North Carolina, United States

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States