Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Parallel Group Clinical Trial to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Mepolizumab (SB240563)(0.55mg/kg, 2.5mg/kg or 10mg/kg) in Pediatric Subjects With Eosinophilic Esophagitis, Aged 2 to 17 Years (Study MEE103219)
Brief Summary: This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous mepolizumab in pediatric subjects with eosinophilic esophagitis.


Options:
A: 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.
B: Inclusion Criteria:

* Diagnosis of eosinophilic esophagitis

Exclusion Criteria:

* Concomitant treatment with swallowed corticosteroids. Any prior use of swallowed corticosteroids will require a 4 week washout period.
* Pregnancy (all females of child bearing potential will have urine pregnancy test done at baseline).
* Evidence of pathologic eosinophilia in other locations in the GI tract.
* Participation in another research protocol
* Reduced Renal or Hepatic Function (all subjects will have a baseline creatinine and liver function panel drawn)
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:

* A subject will be eligible for inclusion in this study only if all of the following criteria apply. Inclusion criteria pertain to all subjects in both cohorts (treatment and observational) unless otherwise stated.
* The subject signs and dates a written assent form (age appropriate) and the parent/guardian signs and dates a written informed consent form prior to the initiation of any study-related activities, including discontinuation of any prohibited medications.
* Male or female subjects aged 2 to 17 years (from 2nd birthday up to and not including 18th birthday), who weigh \<=84.9kg (males)/ \<= 72.5 (females) and who have a BMI between 5 and 85% for age, who speak, read and write English as age appropriate and/or parent/guardian.

NOTE: If subject is within weight requirements but close to the upper or lower limits at screening and the investigator anticipates that during the study the subject's weight will change a become outside the weight requirements, the subject should be excluded from the study.

* To be eligible for entry in the treatment group of the study, a female subject is eligible to enter the study if she is: not pregnant or nursing; of non-childbearing potential. Non-childbearing potential is defined as a pre-menarcheal female who has not yet entered puberty as evidenced by lack of breast development (palpable glandular breast tissue); or a female who has documentation (medical report verification) of hysterectomy and/or bilateral oophorectomy; of childbearing potential. These females subjects must have a negative urine pregnancy test at the screening visit, and agree to consistent and correct use of one of the acceptable methods of birth control from at least the commencement of their last normal period prior to the first dose of study medication and to continue until the first normal period after treatment or after the Week 24 Follow-up visit, whichever is longest.
* The subject has a diagnosis of eosinophilic esophagitis and current evidence on biopsy of isolated eosinophilic esophagitis defined as:
* Peak esophageal eosinophil counts (highest count of eosinophils per HPF in at least one of all esophageal sites biopsied) of 20 or more eosinophils in a minimum of one HPF at 400X magnification on histology of esophageal biopsies from distal and mid-esophagus within two weeks of commencing study medication, as determined by the central histopathologist.
* Inadequate response to or intolerant of therapy for eosinophilic esophagitis
* The individual investigators will apply their clinical judgment to define whether a clinical response to therapy for eosinophilic esophagitis is inadequate. As guidance, inadequate response might consist of persistence under current or recent prior therapy, of symptoms of eosinophilic esophagitis such as eosinophilic esophagitis-related pain in stomach, chest or throat; regurgitation; vomiting; pain or difficulties associated with drinking fluids or nutritional supplements; or pain or difficulties associated with eating. An inadequate response might also consist of persistent eosinophilic infiltration of the esophagus, in the presence or in the absence of eosinophilic esophagitis-related symptoms.
* Similarly, the individual investigators will apply their clinical judgment to define whether a patient is intolerant to therapy. For guidance, intolerance to therapy for eosinophilic esophagitis may consist of undesirable side-effects of long-term therapy; or side-effects of long-term therapy that are difficult to manage; or marked non-compliance to therapy or rejection of therapy by the individual patient, or by the parent/guardian, which in the opinion of the investigator interferes with the patient's optimal disease management.
* The criteria used by the investigator to define inadequate response to or intolerance of therapy for eosinophilic esophagitis will be collected in the CRF.

Exclusion Criteria:

* A subject will not be eligible for inclusion in this study if any of the following criteria apply. Exclusion criteria pertain to all subjects in both cohorts (treatment and observational) unless otherwise stated.
* Current evidence of eosinophilic gastrointestinal enteropathy (EGID), other than eosinophilic esophagitis.
* Evidence of gastroesophageal reflux disease, or other causes of esophagitis which in the investigator's opinion is the predominant cause of the subject's esophageal eosinophilia so that the investigator's opinion is allowed.
* Current presence, or history of (anytime in the past): hypereosinophilic syndromes, collagen vascular disease, vasculitis, allergic drug reaction as the cause of the peripheral eosinophilia, graft-versus host disease, chronic idiopathic inflammatory bowel disorders (ulcerative colitis, Crohn's disease, chronic granulomatous disease).
* Current evidence, or history of celiac disease.
* Current evidence of active H. pylori infection.
* Abnormal 12-lead ECG at Screening which is clinically significant in the opinion of the investigator. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Use or administration of any of the prohibited medications from Screening and throughout completion of Week 34 follow-up. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Failure to remain on a stable dose of one (or more) permitted medication(s) for at least 1 month prior to the Screening visit and throughout completion of Week 24 follow-up assessments. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Failure to remain on stable elemental diet or dietary manipulations for at least 3 months prior to the Screening Visit and throughout completion of Week 34 follow-up assessments. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Known history of allergic reaction to previous antibody therapy.
* Any previous treatment with anti-hIL-5, anti-IgE monoclonal antibody or other biological agents.
* Use of an investigational drug within 30 days of entering the study. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Exhibits evidence of renal disease or serum creatinine \> 1.5 times upper limit of normal range (ULN). Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Exhibits evidence of hepatic disease, impairment or abnormal liver function test i.e. AST, ALT \>1.5 times ULN, bilirubin \>1.5 times ULN. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Known evidence of the following infections/infestations: HIV, Hepatitis B or C, Bacterial infection, Parasitic infestation.
* History or suspicion of current drug abuse and alcohol abuse within the last 6 months.

Answer: D