Dupilumab in Eosinophilic Gastritis

• ClinicalTrials.gov Identifier: NCT03678545
• Recruitment Status: Recruiting
• First Posted: September 19, 2018
• Last Update Posted: June 21, 2022
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Regeneron Pharmaceuticals; National Institutes of Health (NIH)
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Eosinophilic Gastritis; Eosinophilic Gastroenteritis	Drug: Dupilumab (blinded); Drug: Placebo (blinded); Drug: Dupilumab (open-label)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to either drug or placebo, followed by an open label extension
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy of Dupilumab (Anti-IL4a) in Subjects With Eosinophilic Gastritis
• Actual Study Start Date: May 15, 2021
• Estimated Primary Completion Date: January 1, 2023
• Estimated Study Completion Date: July 1, 2023

Arms and Interventions

Arm	Intervention/treatment
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.
Placebo Comparator: Placebo	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.; 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.

Outcome Measures

Primary Outcome Measures :

1. Relative change of peak eosinophil counts in the stomach [ Time Frame: 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 :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Regina Yearout; 513-517-2108; regina.yearout@cchmc.org

Contact: Kara Kliewer; kara.kliewer@cchmc.org

Locations

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Rachel Andrews 720-777-1994 rachel.andrews@childrenscolorado.org

Principal Investigator: Calies Menard-Katcher, MD

University of Colorado Denver and Hospital; Recruiting

Aurora, Colorado, United States, 80045

Contact: Jonathon Cahoon 303-724-8974 jonathon.cahoon@cuanscnutz.edu

Principal Investigator: Paul Menard-Katcher, MD

United States, Illinois

Northwestern Medicine Digestive Health Center; Recruiting

Chicago, Illinois, United States, 60611

Contact: Amanda Jarosik 312-695-4054 amanda.jarosik@northwestern.edu

Principal Investigator: Nirmala Gonsalves, MD

United States, Indiana

Riley Children's Hospital; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Gail Waltz 317-944-9656 gwaltz@iu.edu

Principal Investigator: Sandeep Gupta, MD

United States, Massachusetts

Tufts Medical Center; Completed

Boston, Massachusetts, United States, 02111

United States, North Carolina

University of North Carolina School of Medicine; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Sean LaFata 919-843-7684 sean_lafata@med.unc.edu

Principal Investigator: Evan Dellon, MD

United States, Ohio

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

Contact: Regina Yearout 513-517-2108 Regina.Yearout@cchmc.org

Contact: Kara Kliewer, PhD Kara.Kliewer@cchmc.org

Principal Investigator: Marc E Rothenberg, M.D., PhD

United States, Pennsylvania

The Children's Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Susan Lee 215-528-7314 Leess@chop.edu

Principal Investigator: Jonathan Spergel, MD, PhD

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Maureen DeMarshall 215-349-8546 demarshm@pennmedicine.upenn.edu

Principal Investigator: Gary Falk, MD

United States, Texas

Texas Children's Hospital; Recruiting

Houston, Texas, United States, 77030

Contact: Amanda Vega 832-824-0939 amandav@bcm.edu

Principal Investigator: Carla Davis, MD

United States, Utah

University of Utah Hospital; Recruiting

Salt Lake City, Utah, United States, 84132

Contact: Brinnlie Harward 801-585-0894 brinnlie.harward@hsc.utah.edu

Principal Investigator: Kathryn Peterson, MD

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Regeneron Pharmaceuticals

National Institutes of Health (NIH)

More Information

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT03678545
• Other Study ID Numbers: IRB 2020-0798
• First Posted: September 19, 2018
• Last Update Posted: June 21, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastroenteritis; Gastritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases; Esophagitis; Esophageal Diseases; Leukocyte Disorders; Hematologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Intestinal Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs