Dupilumab in Eosinophilic Gastritis

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Eosinophilic Gastritis; Eosinophilic Gastroenteritis
• Intervention / Treatment: Drug: Dupilumab (blinded); Drug: Dupilumab (open-label); Drug: Placebo (blinded)

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 Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Regina Yearout; Phone Number: 513-517-2108; Email: Regina.Yearout@cchmc.org
• Study Contact Backup: Name: Kara Kliewer; Email: kara.kliewer@cchmc.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver and Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine Digestive Health Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Dupilumab (open-label); 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.; Drug: Placebo (blinded); 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.
Active Comparator: Dupilumab	Drug: Dupilumab (blinded); Subcutaneous injection every two weeks as follows: 600 mg initial dose, and 300 mg subsequent doses for a total of 6 injections.; Drug: Dupilumab (open-label); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Institutes of Health (NIH); Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2021
• Primary Completion (Estimated): March 10, 2024
• Study Completion (Estimated): November 20, 2024

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Hypersensitivity; Esophageal Diseases; Esophagitis; Leukocyte Disorders; Gastritis; Gastroenteritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: IRB 2020-0798

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: data will be collected from 14 different sites and kept in a secure electronic database supported by the NIH: Rare Diseases Data Management and Coordinating Center. Information such as test results, eligibility and patient reported outcomes can be accessed by authorized personnel from each site. staff from each site will only have access to the data collect by that site. The main site, CCHMC, will have full access to all data collected from all sites.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No