Dupilumab in Eosinophilic Gastritis

• ClinicalTrials.gov Identifier: NCT03678545
• Recruitment Status: Not yet recruiting
• First Posted: September 19, 2018
• Last Update Posted: July 22, 2020
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

Study Description

Brief Summary:

40 participants with Eosinophilic Gastritis 18-60 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 nine 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
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: January 2024
• Estimated Study Completion Date: July 2024

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. Mean peak eosinophil counts in the stomach [ Time Frame: 12 weeks ]
   We will determine the mean of the peak eosinophil counts in the 5 most eosinophil dense HPFs in the gastric antrum, body, and/or incisura. Comparison 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:

• Able to give written informed consent
• Willing and able to comply with study visits and activities.
• Age 12-70 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, with no other known cause for gastric eosinophilia; involvement of eosinophilic inflammation in other gastrointestinal segments will be allowed but not required or sufficient.
• Ongoing clinical symptoms (i.e., abdominal pain, bloating, vomiting, diarrhea) prior to enrollment that are not adequately managed by current therapeutic regimen, in the opinion of the patient and investigator.
• Stable medical management of EG (and other eosinophilic disorders, if applicable) including stable dosage of medications in the 30 days prior to study enrolment. Subjects may be on baseline anti-EG therapy (such as elimination diet, elemental diet, proton pump inhibitors, topical or systemic glucocorticoids, immunosuppressive agents, cromolyn, and anti-histamines) as long as there is agreement not to change their dosage unless medically indicated.
• Willing to maintain current dietary regimen throughout the course of the study.
• Women of childbearing potential (WOCBP) and male subjects who are sexually active and non-sterile must agree to use an acceptable method of contraception from Screening until 16 weeks after their last dose.

Exclusion Criteria:

• Concurrent H. pylori gastritis or parasitic infection
• Other gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease
• Hypereosinophilic syndrome, defined by multiple organ involvement (with the exception of atopic disease or EGID) and persistent blood absolute eosinophil count ≥1500/mcL.
• History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained. Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• Current or recent use of biological agents (<5 half-lives prior to screening)
• Current or recent use of any investigational drug (30 days or 5 half-lives, whichever is longer, prior to screening)
• History of anaphylaxis to any biologic therapy or vaccine
• Current pregnancy or breastfeeding
• A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
• Any other medical illness that precludes study involvement

Contacts and Locations

Locations

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Regeneron Pharmaceuticals

More Information

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT03678545
• Other Study ID Numbers: IRB 2018-4246
• First Posted: September 19, 2018
• Last Update Posted: July 22, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: data will be collected from nine 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