|Principal Investigator: Kathryn Peterson|
|Keywords: mepolizumab , eosinophilic espohagitis , dysphagia-predominant||Department: Gastroenterology|
|IRB Number: 00119857|
|Sub Specialties: Esophageal Diseases|
|Recruitment Status: Not yet recruiting|
To determine whether mepolizumab is more effective than placebo for improving symptoms of dysphagia and decreasing esophageal eosinophil counts in adults and adolescents with active eosinophilic esophagitis after an initial 3 month treatment course, and will also assess the impact of an additional 3 months of treatment.
1. To determine whether mepolizumab is more effective than placebo for improving symptoms of dysphagia as measured by the validated Eosinophilic Esophagitis Symptom Activity Index (EEsAI) in adults and adolescents with active eosinophilic esophagitis after a 3 month treatment course.
2. To determine whether mepolizumab is more effective than placebo for decreasing esophageal eosinophil counts in adults and adolescents with active eosinophilic esophagitis after a 3 month treatment course.
1. To determine predictors of symptomatic and histologic response to mepolizumab treatment, including potential biomarkers.
2. To assess durability of symptomatic and histologic response to mepolizumab after 6 months of treatment in patients initially randomized to the active medication (this includes a 3 month blinded second phase of treatment).
3. To assess histologic response to a lower dose of mepolizumab treatment in patients initially randomized to the placebo arm (this will be in a 3 month blinded second phase); symptom response will also be assessed in this phase.
4. To assess safety of mepolizumab over 3 and 6 months of treatment (this includes both 3 month study phases).
1. Age 16-75* (our site will only enroll 18-75)
2. Diagnosis of EoE as per consensus guidelines (including PPI non-response).2, 43
3. Active eosinophilia on esophageal biopsy, with a peak count of least 15 eos/hpf from at least one esophageal level.**
4. Biopsies from the stomach and duodenum that have ruled out alternative etiologies in all children and in adults with abnormal endoscopic findings or when other gastric or small intestinal conditions are clinical possibilities. If these samples have been obtained during a previous endoscopic evaluation and in the judgement of the investigator the patient has not had a clinically significant change that would merit repeat gastric/duodenal biopsies, then prior normal gastric and duodenal biopsies are acceptable to exclude alternate etiologies.
5. Active symptoms of dysphagia with more than 3 episodes of dysphagia over a period of 2 weeks during the screening period, and an Eosinophilic Esophagitis Symptom Activity Index (EEsAI; see below for details) score of ≥ 27 at baseline.***
6. Able to read, comprehend, and sign consent form.
7. Have maintained a stable diet for 6 weeks prior to enrollment.****
8. Able to maintain a stable diet throughout the duration of the study period. ****
9. Female subjects of childbearing potential who have had their first menses agree to use a highly effective method of birth control during the study and for 30 days after the last dose of study drug. Female subjects with reproductive potential who are using systemic contraceptives (e.g., oral contraceptives, injectable contraceptives, implantable/insertable hormonal contraceptive products, or transdermal patches) to prevent pregnancy must have stable use for ≥28 days prior to screening.
* The rationale for this criterion is that adolescents and adults with EoE have a very similar clinical presentation with dysphagia-predominant symptoms.21 If we were to enroll younger patients there would be few who would meet the dysphagia threshold, and the symptom metric we will use was not validated in younger patients.42 Patients of any age can have EoE, but in patients above the age of 75 malignancy is a concern with clinical symptoms of dysphagia, and EoE becomes less common.
**PPI non-response is defined as >15 eos/hpf after at least 6 weeks of high dose administration (40mg total per day or higher) of any approved PPI medication or documented evidence of intolerance or allergy to PPIs. The length of the PPI trial period or documented intolerance/allergy will be determined according to the local clinical standard of care.
*** The rationale for this criterion is to ensure high levels of esophageal eosinophilia at baseline. For this study, baseline symptoms are gathered during the screening visit and used as baseline measurements.
**** The rationale for this criterion is to ensure that highly symptomatic patients are enrolled, and based on this threshold and prior data related to the EEsAI, we would expect baseline scores for this patient population in the 50-60 range.
***** As dietary restriction is a known effective treatment for EoE, and signs and symptoms of EoE may be highly dependent on eating behaviors, patients should maintain a stable diet for at least 6 weeks preceding enrollment and throughout the duration of the study period.
An individual who meets any of the following criteria will be excluded from participation in this study:
1. Esophageal dilation within 8 weeks of the screening endoscopy.
2. Inability to pass a standard upper endoscope (8-10mm) due to esophageal narrowing or stricturing.
3. Swallowed/topical steroids for EoE within 4 weeks of the screening endoscopy, or a course of systemic corticosteroids within 8 weeks of the screening endoscopy.*
*A course is defined as more than 3 days of systemic steroid use. Subjects who have received >3 days of steroids may be eligible if, in the investigator's opinion, the steroid use does not impact the assessment of the underlying EoE disease activity.
4. Not having maintained a stable diet for at least 6 weeks preceding the screening endoscopy.
5. Initiation, discontinuation, or change of dose regimen of PPIs; leukotriene inhibitors; or nasal, inhaled, and/or orally administered topical corticosteroids** for any condition (such as gastroesophageal reflux disease, asthma, or allergic rhinitis) within the 8 weeks prior to the qualifying EGD.
**Subjects with a documented history of non-response to steroid treatment for EoE may be eligible if, in the investigator's opinion, the non-EoE steroid treatment would not impact the assessment of the underlying EoE disease activity.
Sponsor-investigator approval is required prior to randomization for subjects who have received any steroids in the 8 weeks prior to the screening EGD or before randomization.
6. Presence of concomitant eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic colitis (EC), Crohn’s disease, ulcerative colitis, or celiac disease.
7. History of malignancy within 5 years prior to screening, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
8. History of achalasia.
9. Prior esophageal surgery.
10. History of bleeding disorder or esophageal varices.
11. Active parasitic infection or suspicion of an active parasitic infection, which, in the opinion of the investigator, has not been previously evaluated or treated. Subjects presenting with signs of active parasitic infection or suspicion of active parasitic infection as assessed by current diarrhea and/or blood or mucus in stool will be referred to their clinical physician for further testing to rule out parasitic infection.
12. Any other active infections judged at the discretion of the site-Investigator.
13. Any other medical or psychological condition that, in the opinion of the site-investigator, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical trial, may make patient’s participation unreliable, or may interfere with study assessments. The specific justification for patients excluded under this criterion will be noted in study documents.
14. Patient or his/her immediate family is a member of the investigational team.
15. Pregnancy or breastfeeding.
16. Women of children bearing potential who are not on highly-effective contraception.