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Dupilumab in Eosinophilic Gastritis

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

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.

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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

Resource links provided by the National Library of Medicine

Drug Information available for: Dupilumab

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.




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03678545


Contacts
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Contact: Regina Yearout 513-517-2108 regina.yearout@cchmc.org
Contact: Kara Kliewer kara.kliewer@cchmc.org

Locations
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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)
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03678545    
Other Study ID Numbers: IRB 2020-0798
First Posted: September 19, 2018    Key Record Dates
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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