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.

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.

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.

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.