Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison of Esomeprazole to Aerosolized, Swallowed Fluticasone for Eosinophilic Esophagitis
Brief Summary: Eosinophilic esophagitis (EE) is a recently recognized entity. It has been thought to be related to both allergies and acid reflux. There have been reports that both swallowed, aerosolized steroids and proton pump inhibitors have been effective treatments. The researchers propose to directly compare the efficacy of aerosolized fluticasone to esomeprazole in the treatment of eosinophilic esophagitis. The hypothesis is that aerosolized fluticasone (Flovent) will be more effective in relieving symptoms of EE than esomeprazole (Nexium) treatment. Patients will undergo endoscopy, pH monitoring and manometry for diagnosis. Following diagnosis of EE by pathology (biopsy of esophagus), patients will be randomized to esomeprazole or swallowed fluticasone for 8 weeks. At the end of 8 weeks, subjects will be asked to repeat upper endoscopy with biopsies. Three questionnaires (dysphagia, gastroesophageal reflux disease \[GERD\], and allergy) will be completed by the patient at the first endoscopy and at the end endoscopy. The primary objective is to measure change in eosinophil infiltration of the esophagus in response to treatment of allergy (swallowed fluticasone) versus treatment for reflux (esomeprazole) in EE patients.


Options:
A: Key inclusion criteria:

1. Documented diagnosis of EoE by endoscopy prior to or at screening
2. History of on average at least 2 episodes of dysphagia (with intake of solids off anti-inflammatory therapy) per week in the 4 weeks prior to screening and on average at least 2 episodes of documented dysphagia per week in the weeks between screening and baseline; dysphagia is defined as trouble swallowing solid food, or having solid food stick, by participant report
3. Must remain on a stabilized diet for at least 6 weeks prior to screening and during the course of the study; stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups
4. Documented history of or presence of any of the following: allergic disease (e.g, allergic asthma, allergic rhinitis, atopic dermatitis (AD), or food allergies), peripheral eosinophil counts ≥0.25 GI/L, or serum total Immunoglobulin E (IgE) ≥100 kU/L

Key Exclusion Criteria:

1. Prior participation in a dupilumab (anti-IL-4R) clinical trial
2. Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis
3. History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery prior to screening
4. Any esophageal stricture unable to be passed with a standard, diagnostic, adult (9 to10 mm) upper endoscope or any critical esophageal stricture that requires dilation at screening
5. History of bleeding disorders or esophageal varices
6. Use of chronic aspirin, nonsteroidal agents, or anti-coagulants within 2 weeks prior to screening. Participants should not stop these agents solely to become eligible for entry into this study
7. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening
8. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 3 months prior to screening
9. Use of inhaled (pulmonary or nasal) topical corticosteroids within 3 months prior to screening and during the study, except stable dose for at least 3 months prior to screening biopsy, which cannot be changed during the study
10. Treatment with oral immunotherapy (OIT) within 6 months prior to screening
11. Allergen immunotherapy unless on stable dose for at least 1 year prior to screening
12. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Note: The list of inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial.
B: Inclusion Criteria:

* Male or female subjects aged 12-60 years of age with EE as defined above
* Serum IgE level 30-700 IU/mL
* Subjects with acceptable medical history, physical exam and laboratory test results
* No history of bleeding diathesis, significant cardiopulmonary disease, or other contraindication to upper endoscopy

Exclusion Criteria:

* Need for esophageal dilation at enrollment due to food impaction or inability to pass endoscope
* Inability of subject to provide informed consent (if ages 18-60), or inability of children (ages 12-17) to provide assent
* History of esophagogastric surgery
* Presence of other esophageal pathology that could account for patients' symptoms including eosinophil infiltration due to gastroesophageal reflux disease (GERD)
* Incarceration
* Pregnancy
* Women of childbearing potential not using the contraception method(s)
* Patients with elevated serum IgE levels for reasons other than atopy
* Patients taking cromolyn sodium or nedocromil sodium within 1 month of visit 1
* Patients taking oral or topical corticosteroids within one month of visit 1
* Patients taking leukotriene receptor inhibitors within one month of visit 1
* Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
* Patients with a history of noncompliance to medical regimens or who were considered potentially unreliable
* Use of any other investigational agent in the last 30 days
* Patients with a known hypersensitivity to any ingredient of rhuMAb-E25, study rescue medication
* Patients with Barrett's esophagus will be excluded if found endoscopically or pathologically at biopsy
* Currently treated with omalizumab or treated with omalizumab within the past 6 months.
C: Inclusion Criteria:

* Male or female between ≥18 and ≤75 years of age at the time of informed consent
* Signed informed consent
* Evidence of EoE defined by ≥15 peak eosinophils per HPF as measured from proximal and distal biopsies
* Subject-reported history of ≥3 episodes of dysphagia in the 7 days prior to Screening
* 7-day Global EoE Symptom Score \>3 at baseline and at screening
* Willing and able to adhere to study-related treatment regimens, procedures, and visit schedule

Exclusion Criteria:

* Have known contraindication, hypersensitivity, or intolerance to corticosteroids;
* Have any physical, mental, or social condition or history of illness or laboratory abnormality that in the Investigator's judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study;
* Presence of oral or esophageal mucosal infection of any type;
* Have any mouth or dental condition that prevents normal eating;
* Have any condition affecting the esophageal mucosa or altering esophageal motility other than EoE;
* Use of systemic corticosteroids within 60 days prior to Screening, use of inhaled/swallowed corticosteroids within 30 days prior to Screening, or extended use of high-potency dermal topical corticosteroids within 30 days prior to Screening;
* Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF);
* Morning serum cortisol level ≤5 μg/dL (138 nmol/L);
* Use of biologic immunomodulators in the 24 weeks prior to Screening;
* Use of calcineurin inhibitors or purine analogues, or potent cytochrome P450 (CYP) 3A4 inhibitors in the 12 weeks prior to Screening;
* Have a contraindication to or factors that substantially increase the risk of EGD or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope;
* Have a history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening;
* Have initiated, discontinued or changed dosage regimen of PPIs, H2 antagonists, antacids or antihistamines for any condition such as GERD or allergic rhinitis within 4 weeks prior to qualifying endoscopy. These drugs must remain constant throughout the study.
* A serum cortisol level \<18 μg/dL (497 nmol/L) at 60 minutes with adrenocorticotropic hormone (ACTH) stimulation test using 250 μg cosyntropin (i.e., a positive result on the ACTH stimulation test).
D: Inclusion Criteria:

* Patients aged 18-80 with EE, defined as: a) dysphagia, food impaction or other upper gastrointestinal symptoms (chest pain, heartburn, regurgitation); b) multiple esophageal rings or furrows; c) the presence of \>20 eosinophils/high power field in the squamous epithelium or deeper tissues of the esophagus
* Ability to undergo esophageal manometry and ambulatory pH monitoring
* No history of bleeding diathesis, significant cardiopulmonary disease, or other contraindication to upper endoscopy
* Those who have had a one month holiday from either esomeprazole therapy or fluticasone if they have been prescribed this prior to enrollment

Exclusion Criteria:

* Contraindication to proton pump inhibitors or swallowed fluticasone
* Need for immediate esophageal dilation at enrollment due to food impaction at the discretion of the performing endoscopist
* Inability to pass endoscope
* Pregnancy
* Incarceration
* Inability to provide informed consent
* History of esophago-gastric surgery or prior history of abdominal surgery with subsequent strictures or symptoms of obstruction such as abdominal pain and bloating
* Presence of other esophageal pathology that could account for patients' symptoms as determined by histological interpretation by the pathologist
* History of esophageal spasm resulting in trouble swallowing foods larger than 1 cm in diameter

Answer: D