Eosinophilic Gastritis, Eosinophilic Gastroenteritis
Conditions
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.
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.
Interventions
DRUGDupilumab (blinded)
Subcutaneous injection every two weeks as follows: 600 mg initial dose, and 300 mg subsequent doses for a total of 6 injections.
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.
Sponsors
Regeneron Pharmaceuticals
National Institute of Allergy and Infectious Diseases (NIAID)
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Participants are assigned to either drug or placebo, followed by an open label extension
Eligibility
Sex/Gender
ALL
Age
12 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change of Peak Eosinophil Counts in the Stomach | 12 weeks after randomization | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab Dupilumab (blinded): Subcutaneous injection every two weeks as follows: 600 mg initial dose, and 300 mg subsequent doses for a total of 6 injections. | 21 |
| Placebo 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. | 20 |
| Total | 41 |
Baseline characteristics
| Characteristic | Dupilumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Continuous | 30.3 years STANDARD_DEVIATION 12.9 | 30.7 years STANDARD_DEVIATION 14 | 30.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 21 participants | 20 participants | 41 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 40 |
| other Total, other adverse events | 19 / 21 | 18 / 20 | 37 / 40 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 40 |
Outcome results
Primary
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.
Time frame: 12 weeks after randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dupilumab | Relative Change of Peak Eosinophil Counts in the Stomach | -50.28 Eosinophil per HPF (EOS/HPF) |
| Placebo | Relative Change of Peak Eosinophil Counts in the Stomach | -3.54 Eosinophil per HPF (EOS/HPF) |