Intravenous Mepolizumab In Children With Eosinophilic Esophagitis
Condition: Oesophagitis, Eosinophilic
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Intervention: mepolizumab
Intervention description: Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg), 2.5 mg/kg , or 10 mg/kg by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 84.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: eosinophilic; mepolizumab; esophagitis

Summary:

      This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of
      intravenous mepolizumab in pediatric subjects with eosinophilic esophagitis.
    

Eligibility criteria:

        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.