Intravenous Mepolizumab In Children With Eosinophilic Esophagitis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00358449
• Collaborator: (none)
• Enrollment: 84
• Locations: 29
• Arms: 3
• Actual Duration (Months): 26.5
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Oesophagitis, Eosinophilic	Drug: mepolizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official 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)
• Actual Study Start Date: Sep 11, 2006
• Actual Primary Completion Date: Nov 25, 2008
• Actual Study Completion Date: Nov 25, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab 0.55 mg/kg Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.	Drug: mepolizumab; 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.
Experimental: Mepolizumab 2.5 mg/kg Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Drug: mepolizumab; 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.
Experimental: Mepolizumab 10 mg/kg Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Drug: mepolizumab; 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Events (AE), Any Serious Adverse Event (SAE) and Drug-related AE During Treatment Phase (TP) and Follow-up Phase (FP) [From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)]

   An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event is defined as any untoward medical occurrence that, at any dose that Results in death, life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; a congenital anomaly/birth defect. Drug-related AE's were considered to have a reasonable possibility of being related to treatment by the investigator. AE, SAE and drug-related AEs are summarized by TP and FP.

2. Number of Participants With Indicated Biochemistry Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During Study Period. [From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)]

   Blood samples were collected at Day 1, Weeks 4, 8, 12, 16, 20 and 24 to estimate the following biochemistry parameters: alanine amino transferase (ALT), aspartate amino transferase (AST), albumin (Ab), total protein (ToP), creatinine (Cr), total bilirubin (TB), calcium (Ca), bicarbonate (Bi), chloride (Cl), glucose (Glu), potassium (Pot), and sodium (Sod). Laboratory abnormalities outside the reference range (high and low values) at any time post baseline were presented. Any time post Baseline = all visits (including scheduled and unscheduled). If participant had given both high and low value at least once then participant is counted under both high and low category for this visit.

3. Number of Participants With Indicated Hematology Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During the Study Period. [From first dose of study treatment (Day 1) up to Long-term Follow-up Phase (Week 34)]

   Blood samples were collected pre-infusion at Day 1, Week 4 and Week 8; and 24h and 72h post-infusion at Day 1, Week 4 and Week 8 time points and at Weeks 2, 6, 10, 12, 16, 20, 24, and 34 to estimate the following hematology parameters: basophils (Bas), percentage of basophils (% Bas), lymphocytes (Lym), percentage of Lym (% Lym), monocytes (Mon), percentage of Mon (% Mon), platelet count (PC), total neutrophils (TN), percentage of TN (% TN), white blood cell count (WBC), hematocrit (He), hemoglobin (Hg), and red blood cell count (RBC). Laboratory abnormalities outside the reference range (high and low values) at any time post baseline were presented. Any time post Baseline = all visits (including scheduled and unscheduled). If participant had given both high and low value at least once then participant is counted under both high and low category for this visit.

4. Number of Participants With the Indicated Change From Baseline in ECG Findings at Any Time Post-Baseline [Screening, Weeks 4, 8 and 12]

   12-lead ECG assessments were obtained at the following time points: screening, and Weeks 4, 8 and 12.. Overall ECG findings were summarized using the worst case findings without regard to visits ie. "any time post Baseline". Change from Baseline in ECG findings were categorized as clinically significant change from Baseline; no clinically significant change from Baseline and not applicable.

5. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points [Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24]

   SBP and DBP measurements were obtained at the following time points: screening, pre-infusion, 10 minutes (m), 30m, 1 hour (h), 2h post-infusion on Day 1, Week 4, Week 8; and Weeks 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

6. Change From Baseline in Heart Rate at the Indicated Time Points [Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24]

   Heart rate measurements were obtained at the following time points: Screening, pre-infusion, 10m, 30m, 1h, 2h post-infusion on Day 1, Week 4, Week 8; and Weeks 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

7. Change From Baseline in Temperature at the Indicated Time Points [Screening, Day 1, Weeks 4, 8, 12, 16, 20 and 24]

   Temperature measurements were obtained at the following time points: Screening, Day 1, and Weeks 4, 8, 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

8. Number of Participants With Positive and Negative Anti-mepolizumab Antibody Results at Any Visit and Repeat Visit. [Day 1, Weeks 4, 8, 12, 24, and 34]

   Blood samples for testing anti-mepolizumab antibodies were collected on Day 1, Week 4 and 8 Infusion Visit (before the IV infusion) and at Week 12, 24 and 34 Week follow-up visits. The presence of anti-human mepolizumab antibodies was assessed using an immunoelectrochemiluminescent (ECL) assay. To address transient positive results, an assessment of repeated results were made. For any visit category: results were considered as positive if it was positive at any visit during the study, and results were considered as negative if it were negative at all visits during the study. For repeat visit category: results were considered as postive if the result was positive at >1 visit, and results were considered as negative if the result was negative at all visits or was positive at only one visit.

9. Number of Participants Achieving a Reduction in Peak Esophageal Eosinophil Count to < 5 Cells Per High Power Field (HPF) at Week 12 [Week 12]

   A responder was defined as a participant achieving a reduction in esophageal eosinophils to <5 cells per HPF as the highest count of eosinophils per HPF in all the esophageal sites biopsied at Week 12, confirmed by biopsy at Week 12 or at an early withdrawal visit prior to Week 12. A worst case (WC) approach was considered, if a particiapant withdrew prematurely : If a particiapnt dropped out of the study without having a biopsy taken, due to lack of efficacy or an adverse event, their response was imputed as not achieved. Participants who withdrew, without a biopsy, for other reasons (e.g. lost to follow-up) were considered non-evaluable for the primary analysis. For participants who withdrew early from the study and had a biopsy, the biopsy was used to determine their response.

10. Central (V1), Periperial (V2) and Steady-State (Vss) Volume of Distribution of Mepolizumab [Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug is uniformly distributed to produce the desired plasma concentration of a drug. Central volume of distribution is a hypothetical volume into which a drug initially distributes upon administration. Peripheral volume of distribution is the sum of all tissue spaces outside the central compartment. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 from each participant to estimate central (V1) and periperial (V2) and Steady State (Vss) volume of distribution of mepolizumab.

11. Plasma Clearance (CL) of Mepolizumab [Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34]

    Clearance is defined as the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 from each participant to estimate plasma clearance of mepolizumab.

Secondary Outcome Measures

1. Change From Baseline in Pain in Stomach Severity Scores [Screening, Weeks 9-12 and Weeks 21-24]

   Par.and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A severity score of 0 was assigned for days on which pain in stomach was not experienced. If pain in stomach was reported, severity of pain was assessed as: 1=hurt a little, 2=hurt somewhat, 3=hurt quite a bit, and 4=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as the Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric Analysis of Covariance (ANCOVA) models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction

2. Change From Baseline in Pain in Chest/Throat Severity Scores [Screening, Weeks 9-12 and Weeks 21-24]

   Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A severity score of 0 was assigned for days on which pain in chest/throat was not experienced. If pain in chest/throat was reported, severity of pain was assessed as: 1=hurt a little, 2=hurt somewhat, 3=hurt quite a bit, and 4=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as the Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.

3. Change From Baseline in Percentage of Days With Pain in Stomach [Screening, Weeks 9-12 and Weeks 21-24]

   The percentage of days with the symptom of pain in stomach during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

4. Change From Baseline in Percentage of Days With Pain in Chest/Throat [Screening, Weeks 9-12 and Weeks 21-24]

   The percentage of days with the symptom of pain in chest/throat during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

5. Change From Baseline in Regurgitation Bothersome Scores [Screening, Weeks 9-12 and Weeks 21-24]

   Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 0 was assigned for days on which the symptom regurgitation was not experienced. The days regurgitation experienced, the amount the symptom bothered the Par. was assessed as 1=not bothered at all, 2=bothered a little, 3=somewhat bothered, 4=bothered quite a bit, 5=bothered a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for Baseline score, treatment group, age group interactions

6. Change From Baseline in Percentage of Days With Regurgitation Bothersome Scores [Screening, Weeks 9-12 and Weeks 21-24]

   The percentage of days with the symptom of pain in regurgitation bothersome during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

7. Change From Baseline in Frequency of Vomiting [Screening, Weeks 9-12 and Weeks 21-24]

   Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A participant vomiting any time was counted as one episode of vomiting, irrespective of how close they are to each other. The daily frequency of vomiting was calculated as the total number of times the participant vomited during the interval divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.

8. Change From Baseline in Percentage of Days With Vomiting [Screening, Weeks 9-12 and Weeks 21-24]

   The percentage of days with the symptom of vomiting during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

9. Change From Baseline in Daily Degree of Difficulty With Drinking [Screening, Weeks 9-12 and Weeks 21-24]

   Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned days the participant did not drink. The amount of difficulty with drinking was assessed as 1=no difficulty, 2=a little difficulty, 3=some difficulty, 4=quite a bit of difficulty, 5=a whole lot of difficulty. The average difficulty for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the drinking difficulty scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.

10. Change From Baseline in Pain With Drinking Severity Scores [Screening, Weeks 9-12 and Weeks 21-24]

    Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned the day participant did not drink. The severity of pain was assessed as: 1=didn't hurt at all, 2=hurt a little, 3=hurt somewhat, 4=hurt quite a bit, and 5=hurt a whole lot. The average difficulty and pain severity scores was calculated as the sum of the respective scores for that interval divided by the number of days in the interval. . Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.

11. Change From Baseline in Percentage of Days on Which the Participant Drank [Screening, Weeks 9-12 and Weeks 21-24]

    The percentage of days with the symptom of difficulty and pain when participant drank during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

12. Change From Baseline in Difficulty With Eating Solid Foods [Screening, Weeks 9-12 and Weeks 21-24]

    Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP and FP. A score of 6 was assigned for that symptom when Par. did not eat solid foods. When Par.eat solid foods, the amount of difficulty was assessed as 1=no difficulty, 2=a little difficulty, 3=some difficulty, 4=quite a bit of difficulty, 5=a whole lot of difficulty. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interactions.

13. Change in Baseline in Pain With Eating Solid Foods Severity Scores [Screening, Weeks 9-12 and Weeks 21-24]

    Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned for that symptom when Par. did not eat. The severity of pain was assessed when Par. eats food as: 1=didn't hurt at all, 2=hurt a little, 3=hurt somewhat, 4=hurt quite a bit, and 5=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.

14. Change From Baseline in the Percentage of Days Participants Ate Solid Foods [Screening, Weeks 9-12 and Weeks 21-24]

    The percentage of days with the symptom of difficulty and pain when eating solid foods during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

15. Change From Baseline in Feeling of Something Stuck in Throat Bothersome Scores (for Par. 8-17 Years Only) [Screening, Weeks 9-12 and Weeks 21-24]

    Par. and/or parent/guardian recorded daily symptoms of the feeling like something is stuck in throat on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 0 was assigned for days on which the symptom of feeling of something stuck was not experienced. On days that feeling of something stuck in the throat was experienced, the amount the symptom bothered the Par. was assessed as 1=not bothered at all, 2=bothered a little, 3=somewhat bothered, 4=bothered quite a bit, 5=bothered a whole lot. Average bothersome score was calculated as the sum of the respective scores for that interval divided by the number of days. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age interaction.

16. Change From Baseline in Percentage of Days With Feeling of Something Stuck in Throat (for Par. 8-17 Years) [Screening, Weeks 9-12 and Weeks 21-24]

    The percentage of days with feeling of something stuck in throat during each analysis period (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.

17. Number of Participants With Maintenance of Response [Week 12 and Week 24]

    Participants who achieved a response of <5 esophageal eosinophils/HPF at Week 12 by worst case analysis, were evaluated for maintenance of response of <20 cells/HPF at Week 24. Response categories were defined as: non-responder (did not respond at Week 12 or Week 24); delayed responder (did not respond at Week 12 but responded at Week 24); relapsed (responded at Week 12 but not at Week 24); maintained (responded at Week 12 and Week 24). The following assumptions were made for worst case: if a Participant dropped out of the study due to lack of efficacy or an adverse event and had a missing response, their response was imputed as not achieved (i.e. failure). However for Participants withdrawn for other reasons (e.g. lost to follow-up) with a missing response (i.e. did not have the biopsy) the response was made as missing and not imputed.

18. Mean Change From Baseline in Peak Esophageal Eosinophil Counts at Weeks 12 and 24 [Baseline, Weeks 12 and 24]

    Participants underwent an esophagogastroduodenoscopy (EGD) with biopsies at Screening and at Weeks 12 and 24. Peak esophageal eosinophils were calculated as the maximum count across all esophageal biopsies at each time point. Screening value was considered as the Baseline value. Change from baseline was calculated as the post-Baseline value minus the Baseline value.

19. Change From Baseline in Mean Esophageal Eosinophil Counts at Weeks 12 and 24 [Baseline, Weeks 12 and 24]

    Participants underwent an EGD with biopsies at Screening and at Weeks 12 and 24. Mean esophageal eosinophils were calculated as the mean number across all esophageal biopsies at each time point. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

20. Absolute Blood Eosinophils Count at the Indicated Time Points [Screening, Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34]

    Blood samples were obtained at Screening, pre-infusion and 24h and 72-96h post-infusion at Day 1, Weeks 4 and 8; and at Week 2, 6, 10, 12, 16, 20, 24 and 34 visits or Early Withdrawal Visit to estimate blood eosinophil count.

21. Plasma Concentration of Mepolizumab [Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34]

    Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 to estimate the plasma concentration of mepolizumab. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35205
2	GSK Investigational Site	San Diego	California	United States	92123
3	GSK Investigational Site	Tampa	Florida	United States	33613
4	GSK Investigational Site	Atlanta	Georgia	United States	30322
5	GSK Investigational Site	Springfield	Illinois	United States	62794
6	GSK Investigational Site	Evansville	Indiana	United States	47713
7	GSK Investigational Site	Indianapolis	Indiana	United States	46202
8	GSK Investigational Site	Worcester	Massachusetts	United States	01655
9	GSK Investigational Site	Southfield	Michigan	United States	48075
10	GSK Investigational Site	Troy	Michigan	United States	48098
11	GSK Investigational Site	Minneapolis	Minnesota	United States	55402
12	GSK Investigational Site	Kansas City	Missouri	United States	64108
13	GSK Investigational Site	Saint Louis	Missouri	United States	63104
14	GSK Investigational Site	New York	New York	United States	10029
15	GSK Investigational Site	Cincinnati	Ohio	United States	45229
16	GSK Investigational Site	Sioux Falls	South Dakota	United States	57108
17	GSK Investigational Site	Dallas	Texas	United States	75230
18	GSK Investigational Site	Dallas	Texas	United States	75235
19	GSK Investigational Site	Norfolk	Virginia	United States	23507
20	GSK Investigational Site	Milwaukee	Wisconsin	United States	53215
21	GSK Investigational Site	Brisbane	Queensland	Australia	4029
22	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 3Z5
23	GSK Investigational Site	Kingston	Ontario	Canada	K7L 5G2
24	GSK Investigational Site	London	Ontario	Canada	N6A 5W9
25	GSK Investigational Site	Montreal	Quebec	Canada	H3T 1C5
26	GSK Investigational Site	Liverpool		United Kingdom	L12 2AP
27	GSK Investigational Site	London		United Kingdom	WC1N 3JH
28	GSK Investigational Site	Sheffield		United Kingdom	S10 2TH
29	GSK Investigational Site	Watford		United Kingdom	WD18 0HB

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Assa'ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG, Aceves SS. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011 Nov;141(5):1593-604. doi: 10.1053/j.gastro.2011.07.044. Epub 2011 Aug 9.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00358449
• Other Study ID Numbers: MEE103219
• First Posted: Jul 31, 2006
• Last Update Posted: Jul 24, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: eosinophilic; mepolizumab; esophagitis
• Additional relevant MeSH terms: Esophagitis; Eosinophilic Esophagitis

Study Results

Participant Flow

Recruitment Details	Participants (par.) who met the eligibility criteria were randomized in to Treatment Cohort (TC) that consisted of a 2-week Screening Phase, a 12-week Treatment Phase, a 12-week Follow-up Phase and a 10-week Long term Follow-up Phase. Eligible par. who chose not to enter TC could be enrolled in an Observational Cohort to be followed for 24 weeks.
Pre-assignment Detail	A total of 77 subjects participated in this study. Of this total, 59 par. were randomized into the TC to receive blinded study medication. An additional 18 subjects elected not to participate in the TC and were enrolled in the Observational Cohort. A total of 113 par. were screened for eligibility, of which 36 were screen failures.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Period Title: Overall Study
STARTED	19	20	20
COMPLETED	15	19	18
NOT COMPLETED	4	1	2

Baseline Characteristics

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg	Total
Arm/Group Description	Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Total of all reporting groups
Overall Participants	19	20	20	59
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	10.4 (4.28)	10.5 (5.15)	10.4 (4.66)	10.4 (4.64)
Sex: Female, Male (Count of Participants)
Female	3 15.8%	6 30%	3 15%	12 20.3%
Male	16 84.2%	14 70%	17 85%	47 79.7%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	0 0%	1 5%	2 10%	3 5.1%
Asian - Central/South Asian Heritage	0 0%	0 0%	1 5%	1 1.7%
White - White/Caucasian/European Heritage	18 94.7%	19 95%	17 85%	54 91.5%
Unknown	1 5.3%	0 0%	0 0%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Events (AE), Any Serious Adverse Event (SAE) and Drug-related AE During Treatment Phase (TP) and Follow-up Phase (FP)
Description	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event is defined as any untoward medical occurrence that, at any dose that Results in death, life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; a congenital anomaly/birth defect. Drug-related AE's were considered to have a reasonable possibility of being related to treatment by the investigator. AE, SAE and drug-related AEs are summarized by TP and FP.
Time Frame	From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population: all participants who gave informed consent, were randomized and received at least one dose of medication.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Any AE, TP	18 94.7%	15 75%	18 90%
Any AE, FP	15 78.9%	9 45%	10 50%
Drug-Related AE, TP	6 31.6%	4 20%	3 15%
Drug-Related AE, FP	3 15.8%	0 0%	0 0%
Any SAE, TP	0 0%	1 5%	2 10%
Any SAE, FP	0 0%	0 0%	1 5%

2. Primary Outcome

Title	Number of Participants With Indicated Biochemistry Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During Study Period.
Description	Blood samples were collected at Day 1, Weeks 4, 8, 12, 16, 20 and 24 to estimate the following biochemistry parameters: alanine amino transferase (ALT), aspartate amino transferase (AST), albumin (Ab), total protein (ToP), creatinine (Cr), total bilirubin (TB), calcium (Ca), bicarbonate (Bi), chloride (Cl), glucose (Glu), potassium (Pot), and sodium (Sod). Laboratory abnormalities outside the reference range (high and low values) at any time post baseline were presented. Any time post Baseline = all visits (including scheduled and unscheduled). If participant had given both high and low value at least once then participant is counted under both high and low category for this visit.
Time Frame	From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
ALT - RR High, n=19 ,20, 20	3 15.8%	0 0%	3 15%
ALT - RR Low, n=19, 20, 20	1 5.3%	0 0%	1 5%
AST - RR High, n=19, 20, 20	5 26.3%	4 20%	7 35%
AST - RR Low, n=19, 20, 20	0 0%	2 10%	0 0%
Ab - RR High, n=19, 20, 20	5 26.3%	1 5%	2 10%
Ab - RR Low, n=19, 20, 20	4 21.1%	3 15%	5 25%
ToP - RR High, n=19, 20, 20	0 0%	2 10%	1 5%
ToP - RR Low, n=19, 20, 20	6 31.6%	4 20%	6 30%
Cr - RR High, n=19, 20, 20	2 10.5%	4 20%	3 15%
Cr - RR Low, n=19, 20, 20	3 15.8%	3 15%	4 20%
TB - RR High, n=19, 20, 20	0 0%	0 0%	0 0%
TB - RR Low, n=19, 20, 20	3 15.8%	3 15%	4 20%
Ca - RR High, n=19, 20, 20	4 21.1%	7 35%	7 35%
Ca - RR Low, n=19, 20, 20	2 10.5%	0 0%	0 0%
Bi - RR High, n=19, 20, 20	6 31.6%	2 10%	2 10%
Bi - RR Low, n=19, 20, 20	0 0%	1 5%	0 0%
Cl - RR High, n=19, 20, 20	1 5.3%	1 5%	1 5%
Cl - RR Low, n=19, 20, 20	1 5.3%	0 0%	0 0%
Glu - RR High, n=19, 20, 20	8 42.1%	8 40%	7 35%
Glu - RR Low, n=19, 20, 20	9 47.4%	7 35%	8 40%
Pot - RR High, n=19, 19, 20	1 5.3%	1 5%	0 0%
Pot - RR Low, n=19, 19, 20	1 5.3%	0 0%	0 0%
Sod - RR High, n=19, 20, 20	0 0%	0 0%	0 0%
Sod - RR Low, n=19, 20, 20	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Indicated Hematology Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During the Study Period.
Description	Blood samples were collected pre-infusion at Day 1, Week 4 and Week 8; and 24h and 72h post-infusion at Day 1, Week 4 and Week 8 time points and at Weeks 2, 6, 10, 12, 16, 20, 24, and 34 to estimate the following hematology parameters: basophils (Bas), percentage of basophils (% Bas), lymphocytes (Lym), percentage of Lym (% Lym), monocytes (Mon), percentage of Mon (% Mon), platelet count (PC), total neutrophils (TN), percentage of TN (% TN), white blood cell count (WBC), hematocrit (He), hemoglobin (Hg), and red blood cell count (RBC). Laboratory abnormalities outside the reference range (high and low values) at any time post baseline were presented. Any time post Baseline = all visits (including scheduled and unscheduled). If participant had given both high and low value at least once then participant is counted under both high and low category for this visit.
Time Frame	From first dose of study treatment (Day 1) up to Long-term Follow-up Phase (Week 34)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Bas - RR High	1 5.3%	2 10%	0 0%
Bas - RR Low	0 0%	0 0%	0 0%
% Bas - RR High	0 0%	3 15%	3 15%
% Bas - RR Low	0 0%	0 0%	0 0%
Lym - RR High	0 0%	1 5%	0 0%
Lym - RR Low	1 5.3%	0 0%	0 0%
% Lym -RR High	12 63.2%	10 50%	12 60%
% Lym -RR Low	2 10.5%	1 5%	4 20%
Mon -RR High	6 31.6%	7 35%	4 20%
Mon - RR Low	3 15.8%	4 20%	5 25%
% Mon -RR High	14 73.7%	12 60%	15 75%
% Mon -RR Low	1 5.3%	3 15%	4 20%
PC - RR High	3 15.8%	4 20%	3 15%
PC - RR Low	1 5.3%	2 10%	0 0%
TN - RR High	2 10.5%	4 20%	6 30%
TN - RR Low	5 26.3%	5 25%	3 15%
% TN - RR High	1 5.3%	1 5%	4 20%
% TN -RR Low	15 78.9%	11 55%	13 65%
WBC - RR High	2 10.5%	5 25%	4 20%
WBC - RR Low	7 36.8%	4 20%	7 35%
He - RR High	0 0%	1 5%	1 5%
He - RR Low	6 31.6%	6 30%	5 25%
Hg - RR High	0 0%	0 0%	1 5%
Hg - RR Low	4 21.1%	4 20%	1 5%
RBC - RR High	0 0%	0 0%	1 5%
RBC - RR Low	4 21.1%	7 35%	7 35%

4. Primary Outcome

Title	Number of Participants With the Indicated Change From Baseline in ECG Findings at Any Time Post-Baseline
Description	12-lead ECG assessments were obtained at the following time points: screening, and Weeks 4, 8 and 12.. Overall ECG findings were summarized using the worst case findings without regard to visits ie. "any time post Baseline". Change from Baseline in ECG findings were categorized as clinically significant change from Baseline; no clinically significant change from Baseline and not applicable.
Time Frame	Screening, Weeks 4, 8 and 12

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Clinically significant change from	1 5.3%	0 0%	0 0%
No clinically significant change from	18 94.7%	20 100%	20 100%
Not applicable	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Description	SBP and DBP measurements were obtained at the following time points: screening, pre-infusion, 10 minutes (m), 30m, 1 hour (h), 2h post-infusion on Day 1, Week 4, Week 8; and Weeks 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
SBP, Day 1 pre-infusion, n= 19, 20, 20	1.2 (10.65)	3.4 (16.10)	7.4 (14.09)
SBP, Day 1, 10m, n= 19, 20, 19	-3.2 (10.82)	0.8 (12.16)	4.8 (15.27)
SBP, Day 1, 30m, n= 19, 20, 20	-1.7 (11.94)	1.6 (12.75)	5.4 (15.53)
SBP, Day 1, 1h, n= 19, 20, 20	1.1 (13.68)	2.0 (13.45)	3.6 (14.55)
SBP, Day 1, 2h, n= 19, 20, 20	-0.6 (10.32)	2.8 (10.08)	2.7 (15.92)
SBP, Week 4 pre-infusion, n= 19, 20, 19	4.2 (8.74)	0.2 (11.04)	5.7 (12.67)
SBP, Week 4, 10m, n= 19, 20, 19	-1.7 (11.32)	-0.8 (15.93)	3.2 (13.62)
SBP, Week 4, 30m, n= 19, 19, 19	1.2 (10.71)	-4.1 (15.26)	2.5 (16.33)
SBP, Week 4, 1h, n= 19, 19, 20	-1.6 (9.91)	-4.8 (12.69)	4.2 (16.44)
SBP, Week 4, 2h, n= 19, 19, 20	-0.7 (8.69)	0.5 (12.99)	2.9 (15.79)
SBP, Week 8 pre-infusion, n= 19, 20, 19	-0.2 (11.18)	1.2 (13.74)	10.4 (13.08)
SBP, Week 8, 10m, n= 19, 20, 19	-1.7 (10.58)	-1.0 (17.12)	3.3 (14.31)
SBP, Week 8, 30m, n= 19, 19, 18	-2.7 (10.29)	0.8 (15.90)	2.2 (15.89)
SBP, Week 8, 1h, n= 19, 19, 17	1.2 (13.30)	-0.6 (14.18)	8.7 (15.73)
SBP, Week 8, 2h, n= 19, 18, 18	0.4 (12.97)	0.3 (13.11)	4.6 (14.41)
SBP, Week 12, n= 18, 20, 20	1.2 (12.27)	2.1 (15.37)	12.1 (15.12)
SBP, Week 16, n= 15, 19, 20	-1.5 (10.33)	2.3 (11.98)	9.7 (18.97)
SBP, Week 20, n= 15, 18, 18	0.7 (8.80)	2.8 (14.96)	13.1 (14.55)
SBP, Week 24, n= 17, 20, 19	2.1 (9.23)	2.5 (12.33)	6.9 (15.13)
DBP, Day 1 pre-infusion, n= 19, 20, 20	-0.1 (8.81)	2.0 (11.23)	1.4 (9.36)
DBP, Day 1, 10m, n= 19, 20, 19	-1.5 (9.03)	-1.2 (11.37)	2.1 (11.98)
DBP, Day 1, 30m, n= 19, 20, 20	-0.2 (7.93)	-1.2 (10.89)	-0.7 (12.11)
DBP, Day 1, 1h, n= 19, 20, 20	-1.7 (8.41)	-1.1 (10.94)	-2.4 (13.43)
DBP, Day 1, 2h, n= 19, 20, 20	-0.1 (7.39)	1.5 (14.34)	-0.4 (12.96)
DBP, Week 4 pre-infusion, n= 19, 20, 19	-0.2 (7.79)	1.3 (9.97)	1.2 (11.46)
DBP, Week 4, 10m, n= 19, 20, 19	-1.5 (8.82)	-1.6 (11.97)	-0.3 (12.71)
DBP, Week 4, 30m, n= 19, 19, 19	-0.4 (10.31)	-1.7 (11.51)	-0.9 (12.10)
DBP, Week 4, 1h, n= 19, 19, 20	-2.0 (7.54)	-3.9 (9.14)	1.5 (13.45)
DBP, Week 4, 2h, n= 19, 19, 20	0.8 (10.21)	1.6 (9.42)	0.5 (14.38)
DBP, Week 8 pre-infusion, n= 19, 20, 19	0.9 (7.92)	-0.7 (9.50)	4.1 (12.01)
DBP, Week 8, 10m, n= 19, 20, 19	-1.7 (7.72)	-2.2 (11.28)	1.7 (15.01)
DBP, Week 8, 30m, n= 19, 19, 18	-2.2 (9.08)	-0.4 (13.68)	-3.3 (14.15)
DBP, Week 8, 1h, n= 19, 19, 17	-2.3 (11.44)	-1.1 (11.97)	0.1 (14.61)
DBP, Week 8, 2h, n= 19, 18, 18	-4.4 (9.66)	-0.9 (11.69)	-1.2 (13.53)
DBP, Week 12, n= 18, 20, 20	-1.9 (9.09)	-1.8 (5.21)	5.5 (14.48)
DBP, Week 16, n= 15, 19, 20	0.6 (10.06)	3.2 (12.39)	3.1 (12.33)
DBP, Week 20, n= 15, 18, 18	-2.5 (7.90)	3.4 (10.05)	3.3 (11.26)
DBP, Week 24, n= 17, 20, 19	-0.2 (9.26)	2.3 (10.02)	3.5 (8.42)

6. Primary Outcome

Title	Change From Baseline in Heart Rate at the Indicated Time Points
Description	Heart rate measurements were obtained at the following time points: Screening, pre-infusion, 10m, 30m, 1h, 2h post-infusion on Day 1, Week 4, Week 8; and Weeks 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Day 1 pre-infusion, n= 19, 20, 20	0.7 (10.29)	4.0 (12.21)	2.3 (10.76)
Day 1, 10m, n= 19, 20, 19	-3.6 (9.39)	1.7 (15.36)	0.1 (12.34)
Day 1, 30m, n= 19, 20, 20	-2.5 (13.02)	3.5 (14.36)	1.9 (11.56)
Day 1, 1h, n= 19, 20, 20	-4.2 (11.51)	3.0 (13.56)	0.9 (15.40)
Day 1, 2h, n= 19, 20, 20	1.6 (11.31)	4.7 (15.08)	-0.5 (12.53)
Week 4 pre-infusion, n= 19, 20, 19	0.4 (19.19)	2.0 (13.13)	1.4 (14.56)
Week 4, 10m, n= 19, 20, 19	-0.9 (13.56)	-1.6 (11.93)	-4.8 (14.83)
Week 4, 30m, n= 19, 19, 19	-1.4 (15.36)	-4.3 (13.67)	-4.0 (9.71)
Week 4, 1h, n= 19, 19, 20	-4.9 (14.08)	-1.8 (12.88)	-2.2 (15.10)
Week 4, 2h, n= 19, 19, 20	-3.3 (14.63)	-0.8 (10.58)	-5.3 (14.26)
Week 8 pre-infusion, n= 19, 20, 19	-3.1 (12.71)	1.5 (12.15)	7.1 (21.13)
Week 8, 10m, n= 19, 20, 19	-2.8 (11.69)	-4.6 (15.37)	0.1 (16.18)
Week 8, 30m, n= 19, 19, 18	-3.8 (12.19)	-2.7 (9.52)	-2.1 (18.73)
Week 8, 1h, n= 19, 19, 17	-6.2 (10.73)	0.3 (11.09)	0.9 (12.46)
Week 8, 2h, n= 19, 18, 18	-5.4 (11.14)	5.7 (10.33)	-0.3 (12.30)
Week 12, n= 18, 20, 20	-1.8 (13.58)	0.3 (13.05)	1.1 (14.37)
Week 16, n= 15, 19, 20	-7.1 (14.64)	6.9 (13.12)	2.9 (12.62)
Week 20, n= 15, 18, 18	-6.1 (17.40)	7.8 (14.81)	1.7 (15.50)
Week 24, n= 17, 20, 19	-2.1 (13.03)	0.5 (13.43)	-0.4 (13.41)

7. Primary Outcome

Title	Change From Baseline in Temperature at the Indicated Time Points
Description	Temperature measurements were obtained at the following time points: Screening, Day 1, and Weeks 4, 8, 12, 16, 20 and 24. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Screening, Day 1, Weeks 4, 8, 12, 16, 20 and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Day 1, n=19, 20, 20	-0.18 (0.472)	0.01 (0.824)	-0.07 (0.758)
Week 4, n=19, 20, 20	-0.44 (1.023)	-0.30 (0.614)	-0.14 (0.909)
Week 8, n=19, 20, 19	-0.44 (0.490)	-0.13 (0.696)	-0.06 (0.819)
Week 12, n=18, 20, 20	0.03 (0.661)	-0.09 (0.671)	-0.08 (0.914)
Week 16, n=15, 17, 20	-0.01 (0.518)	0.05 (0.491)	0.02 (0.753)
Week 20, n=15, 18, 18	0.00 (0.626)	-0.12 (0.696)	-0.12 (0.644)
Week 24, n=17, 20, 19	-0.11 (0.506)	-0.31 (0.668)	-0.12 (0.826)

8. Primary Outcome

Title	Number of Participants With Positive and Negative Anti-mepolizumab Antibody Results at Any Visit and Repeat Visit.
Description	Blood samples for testing anti-mepolizumab antibodies were collected on Day 1, Week 4 and 8 Infusion Visit (before the IV infusion) and at Week 12, 24 and 34 Week follow-up visits. The presence of anti-human mepolizumab antibodies was assessed using an immunoelectrochemiluminescent (ECL) assay. To address transient positive results, an assessment of repeated results were made. For any visit category: results were considered as positive if it was positive at any visit during the study, and results were considered as negative if it were negative at all visits during the study. For repeat visit category: results were considered as postive if the result was positive at >1 visit, and results were considered as negative if the result was negative at all visits or was positive at only one visit.
Time Frame	Day 1, Weeks 4, 8, 12, 24, and 34

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Any Visit- ECL Screening Positive	15 78.9%	15 75%	16 80%
Any Visit- ECL Screening Negative	4 21.1%	5 25%	4 20%
Repeat Visit-ECL Screening Positive	13 68.4%	5 25%	7 35%
Repeat Visit-ECL Screening Negative	6 31.6%	15 75%	13 65%

9. Primary Outcome

Title	Number of Participants Achieving a Reduction in Peak Esophageal Eosinophil Count to < 5 Cells Per High Power Field (HPF) at Week 12
Description	A responder was defined as a participant achieving a reduction in esophageal eosinophils to <5 cells per HPF as the highest count of eosinophils per HPF in all the esophageal sites biopsied at Week 12, confirmed by biopsy at Week 12 or at an early withdrawal visit prior to Week 12. A worst case (WC) approach was considered, if a particiapant withdrew prematurely : If a particiapnt dropped out of the study without having a biopsy taken, due to lack of efficacy or an adverse event, their response was imputed as not achieved. Participants who withdrew, without a biopsy, for other reasons (e.g. lost to follow-up) were considered non-evaluable for the primary analysis. For participants who withdrew early from the study and had a biopsy, the biopsy was used to determine their response.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT Population-WC

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	17	20	20
Number [Participants]	3 15.8%	2 10%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.865
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.04 to 5.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.190
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.01 to 2.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	Central (V1), Periperial (V2) and Steady-State (Vss) Volume of Distribution of Mepolizumab
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug is uniformly distributed to produce the desired plasma concentration of a drug. Central volume of distribution is a hypothetical volume into which a drug initially distributes upon administration. Peripheral volume of distribution is the sum of all tissue spaces outside the central compartment. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 from each participant to estimate central (V1) and periperial (V2) and Steady State (Vss) volume of distribution of mepolizumab.
Time Frame	Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population: all participants who received study medication and for whom mepolizumab sample was obtained and analyzed.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Central volume of distribution (V1)	2.00	2.29	2.14
Peripheral Volume of distribution (V2)	1.36	1.55	1.46
Steady-State Volume of distribution (Vss)	3.37	3.84	3.60

11. Primary Outcome

Title	Plasma Clearance (CL) of Mepolizumab
Description	Clearance is defined as the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 from each participant to estimate plasma clearance of mepolizumab.
Time Frame	Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Mepolizumab 0.55/ 2.5/ 10 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Geometric Mean (95% Confidence Interval) [Liters per Day (L/day)]	0.14	0.15	0.14

12. Secondary Outcome

Title	Change From Baseline in Pain in Stomach Severity Scores
Description	Par.and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A severity score of 0 was assigned for days on which pain in stomach was not experienced. If pain in stomach was reported, severity of pain was assessed as: 1=hurt a little, 2=hurt somewhat, 3=hurt quite a bit, and 4=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as the Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric Analysis of Covariance (ANCOVA) models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The observed case (OC) datasets with incorrect questionnaires excluded were used for the analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n= 15,18,13	-0.277	-0.149	-0.157
Weeks 21-24, n=13,16,11	-0.479	-0.144	-0.268

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.551
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.128
	Confidence Interval	(2-Sided) 95%; -0.303 to 0.560
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.593
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.120
	Confidence Interval	() 95%; -0.331 to 0.572
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.239
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.334
	Confidence Interval	(2-Sided) 95%; -0.232 to 0.901
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.488
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.211
	Confidence Interval	(2-Sided) 95%; -0.401 to 0.823
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

13. Secondary Outcome

Title	Change From Baseline in Pain in Chest/Throat Severity Scores
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A severity score of 0 was assigned for days on which pain in chest/throat was not experienced. If pain in chest/throat was reported, severity of pain was assessed as: 1=hurt a little, 2=hurt somewhat, 3=hurt quite a bit, and 4=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as the Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The OC datasets with incorrect questionnaires excluded were used for the analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.419	-0.063	-0.049
Weeks 21-24, n=13,16,11	-0.524	-0.091	-0.181

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.139
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.356
	Confidence Interval	(2-Sided) 95%; -0.121 to 0.833
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.371
	Confidence Interval	() 95%; -0.133 to 0.874
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.433
	Confidence Interval	(2-Sided) 95%; -0.080 to 0.946
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.219
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.343
	Confidence Interval	(2-Sided) 95%; -0.214 to 0.899
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

14. Secondary Outcome

Title	Change From Baseline in Percentage of Days With Pain in Stomach
Description	The percentage of days with the symptom of pain in stomach during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-14.02	-12.44	-10.11
Weeks 21-24, n=13,16,11	-22.80	-10.97	-7.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; -13.47 to 16.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.622
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.92
	Confidence Interval	(2-Sided) 95%; -12.01 to 19.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.317
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.83
	Confidence Interval	(2-Sided) 95%; -11.86 to 35.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.246
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.10
	Confidence Interval	(2-Sided) 95%; -10.91 to 41.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

15. Secondary Outcome

Title	Change From Baseline in Percentage of Days With Pain in Chest/Throat
Description	The percentage of days with the symptom of pain in chest/throat during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-24.37	-5.09	-10.16
Weeks 21-24, n=13,16,11	-27.12	-9.43	-6.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.28
	Confidence Interval	(2-Sided) 95%; 0.39 to 38.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.21
	Confidence Interval	(2-Sided) 95%; -5.83 to 34.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.078
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.69
	Confidence Interval	(2-Sided) 95%; -2.10 to 37.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.11
	Confidence Interval	(2-Sided) 95%; -0.51 to 42.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

16. Secondary Outcome

Title	Change From Baseline in Regurgitation Bothersome Scores
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 0 was assigned for days on which the symptom regurgitation was not experienced. The days regurgitation experienced, the amount the symptom bothered the Par. was assessed as 1=not bothered at all, 2=bothered a little, 3=somewhat bothered, 4=bothered quite a bit, 5=bothered a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 0) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for Baseline score, treatment group, age group interactions
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The OC datasets with incorrect questionnaires excluded were the primary analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.307	0.017	-0.047
Weeks 21-24, n=13,16,10	-0.387	-0.034	-0.563

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.241
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.324
	Confidence Interval	(2-Sided) 95%; -0.226 to 0.873
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.371
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.260
	Confidence Interval	(2-Sided) 95%; -0.320 to 0.839
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.291
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.353
	Confidence Interval	(2-Sided) 95%; -0.317 to 1.023
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.653
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.176
	Confidence Interval	(2-Sided) 95%; -0.965 to 0.614
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

17. Secondary Outcome

Title	Change From Baseline in Percentage of Days With Regurgitation Bothersome Scores
Description	The percentage of days with the symptom of pain in regurgitation bothersome during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-10.26	3.80	-4.64
Weeks 21-24, n=13,16,10	-13.77	2.28	-19.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.123
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.06
	Confidence Interval	(2-Sided) 95%; -4.00 to 32.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.551
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.62
	Confidence Interval	(2-Sided) 95%; -13.29 to 24.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.04
	Confidence Interval	(2-Sided) 95%; -5.61 to 37.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.666
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.42
	Confidence Interval	(2-Sided) 95%; -30.74 to 19.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

18. Secondary Outcome

Title	Change From Baseline in Frequency of Vomiting
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A participant vomiting any time was counted as one episode of vomiting, irrespective of how close they are to each other. The daily frequency of vomiting was calculated as the total number of times the participant vomited during the interval divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The OC datasets with incorrect questionnaires excluded were used for the analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15, 18, 13	-0.048	0.040	-0.060
Weeks 21-24, n=13, 16, 11	-0.009	-0.004	0.096

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.572
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.088
	Confidence Interval	(2-Sided) 95%; -0.224 to 0.400
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.942
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.012
	Confidence Interval	(2-Sided) 95%; -0.350 to 0.326
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.960
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.005
	Confidence Interval	(2-Sided) 95%; -0.188 to 0.197
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.317
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.105
	Confidence Interval	(2-Sided) 95%; -0.105 to 0.315
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

19. Secondary Outcome

Title	Change From Baseline in Percentage of Days With Vomiting
Description	The percentage of days with the symptom of vomiting during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-2.40	-3.54	-4.56
Weeks 21-24, n=13,16,11	1.62	-2.98	1.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.666
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 95%; -6.39 to 4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.450
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 95%; -7.87 to 3.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.215
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.60
	Confidence Interval	(2-Sided) 95%; -12.00 to 2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.898
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -8.61 to 7.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

20. Secondary Outcome

Title	Change From Baseline in Daily Degree of Difficulty With Drinking
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned days the participant did not drink. The amount of difficulty with drinking was assessed as 1=no difficulty, 2=a little difficulty, 3=some difficulty, 4=quite a bit of difficulty, 5=a whole lot of difficulty. The average difficulty for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the drinking difficulty scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	0.008	0.046	-0.152
Weeks 21-24, n=13,16,11	-0.137	-0.049	-0.070

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.762
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.038
	Confidence Interval	(2-Sided) 95%; -0.217 to 0.294
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.235
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.159
	Confidence Interval	(2-Sided) 95%; -0.426 to 0.108
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.607
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.089
	Confidence Interval	(2-Sided) 95%; -0.259 to 0.436
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.716
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.068
	Confidence Interval	(2-Sided) 95%; -0.308 to 0.443
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

21. Secondary Outcome

Title	Change From Baseline in Pain With Drinking Severity Scores
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned the day participant did not drink. The severity of pain was assessed as: 1=didn't hurt at all, 2=hurt a little, 3=hurt somewhat, 4=hurt quite a bit, and 5=hurt a whole lot. The average difficulty and pain severity scores was calculated as the sum of the respective scores for that interval divided by the number of days in the interval. . Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The OC datasets with incorrect questionnaires excluded were used for the analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.005	0.085	-0.166
Weeks 21-24, n=13,16,11	-0.193	-0.006	-0.118

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.090
	Confidence Interval	(2-Sided) 95%; -0.365 to 0.545
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.161
	Confidence Interval	(2-Sided) 95%; -0.639 to 0.317
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.568
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.187
	Confidence Interval	(2-Sided) 95%; -0.474 to 0.849
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.076
	Confidence Interval	(2-Sided) 95%; -0.643 to 0.794
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

22. Secondary Outcome

Title	Change From Baseline in Percentage of Days on Which the Participant Drank
Description	The percentage of days with the symptom of difficulty and pain when participant drank during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.24	-1.08	0.66
Weeks 21-24, n=13,16,11	-0.04	-1.09	-1.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.515
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -3.45 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.496
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; -1.74 to 3.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.657
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95%; -5.82 to 3.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -6.11 to 4.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

23. Secondary Outcome

Title	Change From Baseline in Difficulty With Eating Solid Foods
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP and FP. A score of 6 was assigned for that symptom when Par. did not eat solid foods. When Par.eat solid foods, the amount of difficulty was assessed as 1=no difficulty, 2=a little difficulty, 3=some difficulty, 4=quite a bit of difficulty, 5=a whole lot of difficulty. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interactions.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.474	-0.174	-0.119
Weeks 21-24, n=13,16,11	-0.427	-0.245	-0.305

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.142
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.300
	Confidence Interval	(2-Sided) 95%; -0.105 to 0.704
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.115
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.354
	Confidence Interval	(2-Sided) 95%; -0.090 to 0.798
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.465
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.182
	Confidence Interval	(2-Sided) 95%; -0.319 to 0.683
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.649
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.121
	Confidence Interval	(2-Sided) 95%; -0.417 to 0.660
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

24. Secondary Outcome

Title	Change in Baseline in Pain With Eating Solid Foods Severity Scores
Description	Par. and/or parent/guardian recorded daily symptoms of eosinophilic esophagitis on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 6 was assigned for that symptom when Par. did not eat. The severity of pain was assessed when Par. eats food as: 1=didn't hurt at all, 2=hurt a little, 3=hurt somewhat, 4=hurt quite a bit, and 5=hurt a whole lot. The average pain severity for the interval (Baseline, Weeks 9-12, Weeks 21-24) was calculated as the sum of the pain severity scores for that interval (including days assigned as 6) divided by the number of days in the interval. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age group interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	-0.493	-0.123	-0.137
Weeks 21-24, n=13,16,11	-0.399	-0.109	-0.271

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.370
	Confidence Interval	(2-Sided) 95%; -0.042 to 0.782
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.356
	Confidence Interval	(2-Sided) 95%; -0.097 to 0.809
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.345
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.290
	Confidence Interval	(2-Sided) 95%; -0.326 to 0.906
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.700
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.128
	Confidence Interval	(2-Sided) 95%; -0.541 to 0.798
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

25. Secondary Outcome

Title	Change From Baseline in the Percentage of Days Participants Ate Solid Foods
Description	The percentage of days with the symptom of difficulty and pain when eating solid foods during each analysis interval (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=15,18,13	3.64	1.85	3.05
Weeks 21-24, n=13,16,11	2.26	0.65	1.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.609
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95%; -8.79 to 5.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.882
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -8.55 to 7.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.595
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.60
	Confidence Interval	(2-Sided) 95%; -7.68 to 4.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.895
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -7.34 to 6.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

26. Secondary Outcome

Title	Change From Baseline in Feeling of Something Stuck in Throat Bothersome Scores (for Par. 8-17 Years Only)
Description	Par. and/or parent/guardian recorded daily symptoms of the feeling like something is stuck in throat on a hand held personal digital assistant (electronic diary) during the Screening Phase, TP, and FP. A score of 0 was assigned for days on which the symptom of feeling of something stuck was not experienced. On days that feeling of something stuck in the throat was experienced, the amount the symptom bothered the Par. was assessed as 1=not bothered at all, 2=bothered a little, 3=somewhat bothered, 4=bothered quite a bit, 5=bothered a whole lot. Average bothersome score was calculated as the sum of the respective scores for that interval divided by the number of days. Screening phase was considered as Baseline interval. Change from Baseline was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA models with terms for the relevant Baseline score, treatment group, age group and treatment by age interaction.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. The OC datasets with incorrect questionnaires excluded were the primary analysis. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=12,12,8	-0.751	-0.238	-0.510
Weeks 21-24, n=11,11,8	-0.785	-0.075	-0.535

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.513
	Confidence Interval	(2-Sided) 95%; -0.028 to 1.055
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.425
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.241
	Confidence Interval	(2-Sided) 95%; -0.369 to 0.852
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.710
	Confidence Interval	(2-Sided) 95%; -0.096 to 1.516
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.250
	Confidence Interval	(2-Sided) 95%; -0.631 to 1.132
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

27. Secondary Outcome

Title	Change From Baseline in Percentage of Days With Feeling of Something Stuck in Throat (for Par. 8-17 Years)
Description	The percentage of days with feeling of something stuck in throat during each analysis period (Baseline, Weeks 9-12 and Weeks 21-24) was calculated as the number of days the symptom was experienced divided by the number of days in the analysis interval, and presented as a percentage (ie, the proportion X 100%). Screening phase was considered as Baseline interval. Change from Baseline for each analysis interval was calculated as the value for that interval minus the value for the Baseline interval. Analysis was performed using parametric ANCOVA model with terms for Baseline score, treatment group, age group and treatment by age group interaction. The OC datasets with incorrect questionnaires excluded were used for the analysis.
Time Frame	Screening, Weeks 9-12 and Weeks 21-24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Weeks 9-12, n=12,12,8	-21.56	-12.11	-17.44
Weeks 21-24, n=11,11,8	-21.33	-10.76	-15.84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.270
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.45
	Confidence Interval	(2-Sided) 95%; -7.77 to 26.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 9-12.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.664
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.12
	Confidence Interval	(2-Sided) 95%; -15.11 to 23.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.381
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.57
	Confidence Interval	(2-Sided) 95%; -13.81 to 34.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.672
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.49
	Confidence Interval	(2-Sided) 95%; -20.87 to 31.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and estimated value are presented for Weeks 21-24.

28. Secondary Outcome

Title	Number of Participants With Maintenance of Response
Description	Participants who achieved a response of <5 esophageal eosinophils/HPF at Week 12 by worst case analysis, were evaluated for maintenance of response of <20 cells/HPF at Week 24. Response categories were defined as: non-responder (did not respond at Week 12 or Week 24); delayed responder (did not respond at Week 12 but responded at Week 24); relapsed (responded at Week 12 but not at Week 24); maintained (responded at Week 12 and Week 24). The following assumptions were made for worst case: if a Participant dropped out of the study due to lack of efficacy or an adverse event and had a missing response, their response was imputed as not achieved (i.e. failure). However for Participants withdrawn for other reasons (e.g. lost to follow-up) with a missing response (i.e. did not have the biopsy) the response was made as missing and not imputed.
Time Frame	Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants were responders at Week 12 were analyzed.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	16	20	20
Non-responder	12 63.2%	18 90%	18 90%
Delayed responder	1 5.3%	0 0%	2 10%
Relapsed	2 10.5%	1 5%	0 0%
Maintained	1 5.3%	1 5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.400
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.111
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

29. Secondary Outcome

Title	Mean Change From Baseline in Peak Esophageal Eosinophil Counts at Weeks 12 and 24
Description	Participants underwent an esophagogastroduodenoscopy (EGD) with biopsies at Screening and at Weeks 12 and 24. Peak esophageal eosinophils were calculated as the maximum count across all esophageal biopsies at each time point. Screening value was considered as the Baseline value. Change from baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Week 12, n=17,20,20	-76.8 (16.13)	-95.2 (19.63)	-78.9 (13.62)
Week 24, n=16,19,19	-26.3 (16.52)	-41.6 (23.71)	-60.1 (15.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-18.3
	Confidence Interval	(2-Sided) 95%; -71.1 to 34.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for Change from Baseline at Week 12

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.633
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -44.6 to 40.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for Change from Baseline at Week 12

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.920
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.3
	Confidence Interval	(2-Sided) 95%; -76.3 to 45.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for Change from Baseline at Week 24

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-33.8
	Confidence Interval	(2-Sided) 95%; -79.2 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for Change from Baseline at Week 24

30. Secondary Outcome

Title	Change From Baseline in Mean Esophageal Eosinophil Counts at Weeks 12 and 24
Description	Participants underwent an EGD with biopsies at Screening and at Weeks 12 and 24. Mean esophageal eosinophils were calculated as the mean number across all esophageal biopsies at each time point. Screening value was considered as the Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame	Baseline, Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Week 12, n=17,20,20	-27.34 (6.323)	-29.97 (6.184)	-34.04 (5.984)
Week 24, n=16, 19, 19	-8.23 (6.449)	-17.48 (7.446)	-26.03 (5.677)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.747
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.63
	Confidence Interval	(2-Sided) 95%; -20.68 to 15.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for change from baseline values at Week 12

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.352
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.70
	Confidence Interval	(2-Sided) 95%; -24.41 to 11.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for change from baseline values at Week 12

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 2.5 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.525
	Comments
	Method	van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.25
	Confidence Interval	(2-Sided) 95%; -29.69 to 11.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for change from baseline values at Week 24

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab 0.55 mg/kg, Mepolizumab 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.071
	Comments
	Method	Van Elteren test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-17.79
	Confidence Interval	(2-Sided) 95%; -35.21 to -0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	P-value, 95% CI, and Estimated value are presented for change from baseline at week 24

31. Secondary Outcome

Title	Absolute Blood Eosinophils Count at the Indicated Time Points
Description	Blood samples were obtained at Screening, pre-infusion and 24h and 72-96h post-infusion at Day 1, Weeks 4 and 8; and at Week 2, 6, 10, 12, 16, 20, 24 and 34 visits or Early Withdrawal Visit to estimate blood eosinophil count.
Time Frame	Screening, Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Screening, n=17,16,20	0.441 (0.2358)	0.524 (0.2579)	0.493 (0.2218)
Day 1 predose, n= 17,19,20	0.419 (0.1620)	0.476 (0.2660)	0.559 (0.2987)
Day 1 24h postdose, n=12,10,14	0.147 (0.0623)	0.158 (0.1156)	0.230 (0.1120)
Day 1 72-96h postdose, n=14,11,11	0.123 (0.0930)	0.151 (0.0823)	0.179 (0.1319)
Week 2, n=19,18,20	0.139 (0.1531)	0.114 (0.0815)	0.111 (0.068)
Week 4 predose, n=19,16,20	0.165 (0.1635)	0.072 (0.0571)	0.062 (0.0381)
Week 4 24h postdose, n=16,14,14	0.093 (0.0690)	0.097 (0.0548)	0.079 (0.0285)
Week 4 72-96h postdose, n=15,15,15	0.081 (0.0666)	0.089 (0.0721)	0.053 (0.0377)
Week 6, n=19,16,20	0.099 (0.0897)	0.060 (0.0678)	0.146 (0.3902)
Week 8 predose, n=19,19,19	0.113 (0.0910)	0.081 (0.0517)	0.052 (0.0385)
Week 8 24h postdose, n=17,14,14	0.077 (0.0645)	0.055 (0.0494)	0.061 (0.0305)
Week 8 72-96h postdose, n= 16,15,13	0.070 (0.0803)	0.045 (0.0566)	0.075 (0.0285)
Week 10, n= 18,18,18	0.100 (0.0872)	0.059 (0.0537)	0.043 (0.0412)
Week 12, n=16,18,20	0.091 (0.0686)	0.070 (0.1116)	0.048 (0.0411)
Week 16, n=15,18,19	0.261 (0.2097)	0.076 (0.0619)	0.078 (0.0517)
Week 20, n=15,17,18	0.478 (0.3944)	0.191 (0.0893)	0.124 (0.0658)
Week 24, n=15,20,18	0.706 (0.4513)	0.389 (0.2756)	0.147 (0.1167)
Week 34, n=14,18,16	0.650 (0.3025)	0.569 (0.2599)	0.575 (0.4268)

32. Secondary Outcome

Title	Plasma Concentration of Mepolizumab
Description	Blood samples were obtained at pre-infusion and 5m, 2h, 24h, 72-96h post-infusion at Day 1, Weeks 4, 8; and Weeks 2, 6 10, 12, 16, 20, 24 and 34 to estimate the plasma concentration of mepolizumab. Only those participants available at specified time points are analyzed (represented as n=X,X,X in the category titles).
Time Frame	Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population: all participants who received study medication and for whom mepolizumab sample was obtained and analyzed.

Arm/Group Title	Mepolizumab 0.55 mg/kg	Mepolizumab 2.5 mg/kg	Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.	Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
Measure Participants	19	20	20
Day 1 5mins postdose, n=18,20,19	11.3 (7.172)	39.56 (19.041)	177.94 (70.581)
Day 1 2h postdose, n=18,19,17	11.34 (3.516)	42.38 (14.895)	192.99 (49.243)
Day 1 24h postdose, n=18,19,16	8.32 (2.428)	30.05 (7.974)	144.26 (43.87)
Day 1 72-96h postdose, n=15,19,17	6.08 (1.907)	22.62 (7.306)	111.87 (30.046)
Week 2, n=17,16,18	3.42 (1.381)	16.08 (4.68)	59.2 (16.636)
Week 4 Predose,n=19,20,19	1.83 (0.643)	9.43 (2.884)	37.29 (21.978)
Week 4, 5 min postdose, n=19,19,18	9.69 (3.097)	61.56 (18.021)	204.93 (69.325)
Week 4 2h postdose, n=19,19,20	10.04 (3.241)	50.75 (12.992)	212.5 (71.48)
Week 4 24h postdose, n=19,15,20	8.07 (2.515)	42.89 (11.337)	189.92 (55.81)
Week 4, 72-96h postdose, n=19,18,17	6.35 (2.497)	34.54 (8.188)	143.47 (38.414)
Week 6, n=17,13,17	3.69 (1.031)	20.13 (6.602)	88.14 (42.311)
Week 8 predose, n=17,16,16	2.48 (0.69)	10.97 (4.072)	50.96 (17.244)
Week 8 5 min postdose, n=19,20,18	12.44 (3.285)	57.3 (18.132)	213.05 (51.882)
Week 8 2h postdose, n=19,19,19	12.45 (3.386)	58.28 (16.981)	217.71 (51.983)
Week 8 24 h postdose, n=18,18,17	9 (2.554)	47.13 (12.09)	173.41 (43.848)
Week 8 72-96h postdose, n=17,19,19	6.89 (1.651)	36.49 (11.133)	145.75 (35.48)
Week 10, n=19,15,16	4.56 (1.192)	20.7 (6.977)	90.38 (26.77)
Week 12, n=14,18,15	2.57 (0.965)	11.19 (3.395)	48.8 (20.314)
Week 16, n=14,16,17	0.79 (0.474)	4.04 (1.768)	16.38 (6.523)
Week 20, n=11,14,15	0.27 (0.16)	1.27 (0.535)	5.76 (2.477)
Week 24, n=8,14,12	0.11 (0.056)	0.67 (0.389)	2.13 (2.368)
Week 34, n=1,5,7	0.06 (NA)	0.08 (0.025)	1.14 (1.882)

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the date of the first dose of study medication up to the Week 12.
Adverse Event Reporting Description	AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment cohort who gave informed consent, were randomized and received at least one dose of study medication.
Arm/Group Title	Mepolizumab 0.55 mg/kg		Mepolizumab 2.5 mg/kg		Mepolizumab 10 mg/kg
Arm/Group Description	Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.		Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.		Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.
All Cause Mortality
	Mepolizumab 0.55 mg/kg		Mepolizumab 2.5 mg/kg		Mepolizumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mepolizumab 0.55 mg/kg		Mepolizumab 2.5 mg/kg		Mepolizumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		1/20 (5%)		2/20 (10%)
General disorders
Chest discomfort	0/19 (0%)		0/20 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Foreign body trauma	0/19 (0%)		1/20 (5%)		0/20 (0%)
Oesophageal injury	0/19 (0%)		0/20 (0%)		1/20 (5%)
Other (Not Including Serious) Adverse Events
	Mepolizumab 0.55 mg/kg		Mepolizumab 2.5 mg/kg		Mepolizumab 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)		14/20 (70%)		18/20 (90%)
Blood and lymphatic system disorders
Any event	2/19 (10.5%)		0/20 (0%)		0/20 (0%)
Lymphadenopathy	2/19 (10.5%)		0/20 (0%)		0/20 (0%)
Ear and labyrinth disorders
Any event	0/19 (0%)		1/20 (5%)		0/20 (0%)
Vertigo	0/19 (0%)		1/20 (5%)		0/20 (0%)
Eye disorders
Any event	1/19 (5.3%)		0/20 (0%)		2/20 (10%)
Conjunctivitis	0/19 (0%)		0/20 (0%)		1/20 (5%)
Eye irritation	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Ocular hyperaemia	0/19 (0%)		0/20 (0%)		1/20 (5%)
Gastrointestinal disorders
Any event	10/19 (52.6%)		8/20 (40%)		7/20 (35%)
Vomiting	5/19 (26.3%)		3/20 (15%)		2/20 (10%)
Diarrhoea	3/19 (15.8%)		4/20 (20%)		1/20 (5%)
Abdominal pain	3/19 (15.8%)		2/20 (10%)		1/20 (5%)
Abdominal pain	2/19 (10.5%)		0/20 (0%)		3/20 (15%)
Nausea	4/19 (21.1%)		0/20 (0%)		1/20 (5%)
Abdominal discomfort	0/19 (0%)		0/20 (0%)		1/20 (5%)
Dyspepsia	0/19 (0%)		0/20 (0%)		1/20 (5%)
Dysphagia	0/19 (0%)		1/20 (5%)		0/20 (0%)
Eosinophilic oesophagitis	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Faeces discoloured	0/19 (0%)		1/20 (5%)		0/20 (0%)
Flatulence	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Gastritis	0/19 (0%)		0/20 (0%)		1/20 (5%)
Haematochezia	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Paraesthesia oral	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Rectal haemorrhage	0/19 (0%)		0/20 (0%)		1/20 (5%)
Stomach discomfort	0/19 (0%)		1/20 (5%)		0/20 (0%)
General disorders
Any event	5/19 (26.3%)		0/20 (0%)		5/20 (25%)
Pyrexia	4/19 (21.1%)		0/20 (0%)		2/20 (10%)
Chest pain	0/19 (0%)		0/20 (0%)		2/20 (10%)
Catheter site pain	0/19 (0%)		0/20 (0%)		1/20 (5%)
Chest discomfort	0/19 (0%)		0/20 (0%)		1/20 (5%)
Fatigue	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Granuloma	0/19 (0%)		0/20 (0%)		1/20 (5%)
Influenza like illness	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Peripheral coldness	0/19 (0%)		0/20 (0%)		1/20 (5%)
Hepatobiliary disorders
Any event	0/19 (0%)		1/20 (5%)		0/20 (0%)
Hyperbilirubinuria	0/19 (0%)		1/20 (5%)		0/20 (0%)
Immune system disorders
Any event	0/19 (0%)		2/20 (10%)		3/20 (15%)
Seasonal allergy	0/19 (0%)		0/20 (0%)		2/20 (10%)
Food allergy	0/19 (0%)		1/20 (5%)		0/20 (0%)
Hypersensitivity	0/19 (0%)		0/20 (0%)		1/20 (5%)
Multiple allergies	0/19 (0%)		1/20 (5%)		0/20 (0%)
Infections and infestations
Any event	10/19 (52.6%)		7/20 (35%)		8/20 (40%)
Nasopharyngitis	5/19 (26.3%)		1/20 (5%)		4/20 (20%)
Ear infection	1/19 (5.3%)		1/20 (5%)		1/20 (5%)
Influenza	1/19 (5.3%)		2/20 (10%)		0/20 (0%)
Pharyngitis streptococcal	1/19 (5.3%)		1/20 (5%)		1/20 (5%)
Sinusitis	2/19 (10.5%)		0/20 (0%)		1/20 (5%)
Upper respiratory tract infection	1/19 (5.3%)		1/20 (5%)		1/20 (5%)
Gastroenteritis viral	0/19 (0%)		0/20 (0%)		2/20 (10%)
Otitis media	2/19 (10.5%)		0/20 (0%)		0/20 (0%)
Bronchitis	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Bronchitis viral	0/19 (0%)		0/20 (0%)		1/20 (5%)
Cellulitis	0/19 (0%)		1/20 (5%)		0/20 (0%)
Eczema infected	0/19 (0%)		0/20 (0%)		1/20 (5%)
Eye infection	0/19 (0%)		1/20 (5%)		0/20 (0%)
Oral candidiasis	0/19 (0%)		1/20 (5%)		0/20 (0%)
Oral herpes	0/19 (0%)		1/20 (5%)		0/20 (0%)
Orchitis	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Otitis externa	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Pneumonia	0/19 (0%)		1/20 (5%)		0/20 (0%)
Tonsillitis	0/19 (0%)		1/20 (5%)		0/20 (0%)
Urinary tract infection	0/19 (0%)		1/20 (5%)		0/20 (0%)
Viral upper respiratory tract infection	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Any event	3/19 (15.8%)		3/20 (15%)		2/20 (10%)
Joint sprain	1/19 (5.3%)		1/20 (5%)		0/20 (0%)
Ankle fracture	0/19 (0%)		1/20 (5%)		0/20 (0%)
Arthropod bite	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Foot fracture	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Foreign body trauma	0/19 (0%)		1/20 (5%)		0/20 (0%)
Muscle strain	0/19 (0%)		1/20 (5%)		0/20 (0%)
Oesophageal injury	0/19 (0%)		0/20 (0%)		1/20 (5%)
Scratch	0/19 (0%)		0/20 (0%)		1/20 (5%)
Investigations
Any event	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Blood urine present	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Metabolism and nutrition disorders
Any event	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Decreased appetite	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Any event	1/19 (5.3%)		0/20 (0%)		2/20 (10%)
Back pain	1/19 (5.3%)		0/20 (0%)		1/20 (5%)
Pain in extremity	0/19 (0%)		0/20 (0%)		1/20 (5%)
Nervous system disorders
Any event	6/19 (31.6%)		2/20 (10%)		6/20 (30%)
Headache	2/19 (10.5%)		2/20 (10%)		4/20 (20%)
Dizziness	1/19 (5.3%)		0/20 (0%)		2/20 (10%)
Aphonia	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Hypersomnia	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Lethargy	0/19 (0%)		0/20 (0%)		1/20 (5%)
Paraesthesia	0/19 (0%)		0/20 (0%)		1/20 (5%)
Psychomotor hyperactivity	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Psychiatric disorders
Any event	0/19 (0%)		1/20 (5%)		1/20 (5%)
Aggression	0/19 (0%)		0/20 (0%)		1/20 (5%)
Insomnia	0/19 (0%)		1/20 (5%)		0/20 (0%)
Renal and urinary disorders
Any event	1/19 (5.3%)		1/20 (5%)		2/20 (10%)
Dysuria	1/19 (5.3%)		0/20 (0%)		1/20 (5%)
Polyuria	0/19 (0%)		0/20 (0%)		1/20 (5%)
Proteinuria	0/19 (0%)		1/20 (5%)		0/20 (0%)
Reproductive system and breast disorders
Any event	2/19 (10.5%)		0/20 (0%)		0/20 (0%)
Dysmenorrhoea	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Menorrhagia	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Testicular pain	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Any event	9/19 (47.4%)		7/20 (35%)		6/20 (30%)
Cough	7/19 (36.8%)		1/20 (5%)		0/20 (0%)
Oropharyngeal pain	4/19 (21.1%)		1/20 (5%)		2/20 (10%)
Nasal congestion	1/19 (5.3%)		3/20 (15%)		1/20 (5%)
Asthma	3/19 (15.8%)		1/20 (5%)		0/20 (0%)
Throat irritation	1/19 (5.3%)		1/20 (5%)		1/20 (5%)
Postnasal drip	0/19 (0%)		1/20 (5%)		1/20 (5%)
Rhinorrhoea	1/19 (5.3%)		0/20 (0%)		1/20 (5%)
Wheezing	0/19 (0%)		2/20 (10%)		0/20 (0%)
Choking	0/19 (0%)		1/20 (5%)		0/20 (0%)
Dysphonia	0/19 (0%)		1/20 (5%)		0/20 (0%)
Epistaxis	0/19 (0%)		0/20 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
Any event	6/19 (31.6%)		3/20 (15%)		1/20 (5%)
Pruritus	3/19 (15.8%)		0/20 (0%)		0/20 (0%)
Hyperhidrosis	1/19 (5.3%)		0/20 (0%)		1/20 (5%)
Photosensitivity reaction	0/19 (0%)		1/20 (5%)		1/20 (5%)
Eczema	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Erythema	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Pruritus generalised	0/19 (0%)		1/20 (5%)		0/20 (0%)
Rash generalised	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Skin exfoliation	0/19 (0%)		1/20 (5%)		0/20 (0%)
Vascular disorders
Any event	1/19 (5.3%)		0/20 (0%)		0/20 (0%)
Phlebitis	1/19 (5.3%)		0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.