A Study of Benralizumab in Patients With Eosinophilic Esophagitis

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04543409

Acronym

MESSINA

Enrollment

211

Registered

2020-09-10

Start date

2020-09-22

Completion date

2023-02-06

Last updated

2023-11-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Eosinophilic Esophagitis

Keywords

Eosinophilic Esophagitis, EoE, Benralizumab

Brief summary

The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week open-label treatment period). It is proposed that benralizumab will deplete eosinophils from GI tissue(s), improve the symptoms of dysphagia, and improve endoscopy scores as well as other markers of disease activity. Upon completion of the initial 52-week treatment period, patients will be offered an additional Open Label Extension period of at least 1 year, with benralizumab treatment and ongoing study assessments.

Interventions

BIOLOGICALBenralizumab

Solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

BIOLOGICALMatching placebo

Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form. * Documented previous diagnosis of EoE by endoscopy. * Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization): 1. A patient reported an average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND 2. An average of at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) between Visit 1 and Visit 2, and at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) in each of the 2 weeks immediately prior to randomization * May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to the screening and there is agreement not to change type of background medication or dosage during the run-in period and for the first 52 weeks of the study unless a change is medically indicated. * Negative serum pregnancy test for female patients of childbearing potential at Visit1. * Women of childbearing potential must agree to use a highly effective form of birth control (confirmed by the Investigator) from randomization throughout the study duration and within 12 weeks after last dose if IP.

Exclusion criteria

* Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease. * Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period. * Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery that would impact the assessments for EoE * Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period. * Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count \>1500 eos/μL. * EGPA vasculitis. * Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy. * Current malignancy, or history of malignancy with some specific exceptions. * History of anaphylaxis to any biologic therapy or vaccine. * Current active liver disease: * Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen \[HBsAg\] or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period. * Helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent or assent (if applicable) is obtained that has not been treated with or has failed to respond to standard of care therapy. * History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. * Concomitant use of immunosuppressive medication. * Initiation or change of a food-elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to start of the run-in period. * Currently pregnant, breastfeeding, or lactating women.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.	Week 24, Week 52	Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count \<= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders. The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.
Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)	Week 24, Week 52	The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing. The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).

Secondary

Measure	Time frame	Description
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Week 52	In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), patients report on whether they experienced episodes of difficulty swallowing in the past 24 hours and if so, how many. Patients respond to 3 questions on the pain, discomfort, and overall severity of the event using a numeric rating scale (0 \[no\] to 10 \[worst\]). This is repeated for each episode reported. Each category score is calculated as the sum of daily average values in the 14-day period divided by the number of days with available episodes of difficulty swallowing episodes during the same 14-day period (each of the three final scores range from 0 to 10, with higher values indicating a worse outcome in that category). Requires at least 8 days of evaluable data during the period; otherwise, the mean scores are set to missing. Days with 0 episodes of difficulty swallowing count as evaluable. In case all 14 days with 0 episode of difficulty swallowing, the score is set to missing.
Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.	Week 24, Week 52	Percent of patients with any relevant concomitant procedures or healthcare resource utilization for Eosinophilic esophagitis (EoE) or an EoE-related episode (e.g., an intervention for food impaction or stricture requiring dilatation) since last healthcare resource utilization assessment during the previous scheduled visit. Assessed at Week 24 and Week 52.
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Week 24	Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are no symptoms, very mild, mild, moderate, severe, and very severe. The number analyzed represents the participants with evaluable PGI-S results at that timepoint.
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Week 52	Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are no symptoms, very mild, mild, moderate, severe, and very severe. The number analyzed represents the participants with evaluable PGI-S results at that timepoint.
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Week 24	Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are much better, moderately better, a little better, about the same/no change, a little worse, moderately worse, and much worse. The number analyzed represents the participants with evaluable PGI-C results at that timepoint.
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Week 52	Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are much better, moderately better, a little better, about the same/no change, a little worse, moderately worse, and much worse. The number analyzed represents the participants with evaluable PGI-C results at that timepoint.
Percent Change From Baseline in Tissue Eosinophils	Week 24, Week 52	Percent change from baseline in tissue eosinophils (eos) at Week 24 and Week 52. The number analyzed represents the number of participants with data at that visit (including imputed values).
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24	Week 24	EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total grade score (TGS): mean of the grade score ratios per region. Grade score ratio per region is the sum of all available feature grade scores divided by the maximum possible score. The maximum possible total grade score is 1. The number analyzed represents the number of participants with data at that visit (including imputed values).
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24	Week 24	EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total stage score (TSS): mean of the stage score ratios per region. Stage score ratio per region is the sum of all available feature stage scores divided by the maximum possible score. The maximum possible total stage score is 1. The number analyzed represents the number of participants with data at that visit (including imputed values).
Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)	Week 24, Week 52	EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EoE.The score ranges from 0 (normal) to 9 (severe disease). EREFS total score (TS): The worst score for each individual component from the proximal and distal scores were summed to form the EREFS total score (TS). The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).
Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24	Week 24	Percentage of participants with a treatment response at Week 24. A treatment response is defined as composite of histologic response and clinically meaningful improvement (30% reduction) from baseline in DSQ score. Participants with missing data at Week 24 or with intercurrent events prior to Week 24 are considered non-responders.
Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	Week 24	Esophagogastroduodenoscopy biopsies were collected at week 24 and sent to the central lab for slide preparation and for central, blinded pathology review of tissue eosinophil counts and histopathology. Centralized slide assessments and scoring from an independent physician review was performed for all biopsies.
Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)	Week 24, Week 52	Dysphagia free days is a count ranging from 0-28. Higher counts indicate better outcomes. The number analyzed represents the number of participants with data at that visit.
Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)	Week 24, Week 52	EoE-3D is a daily diary focused on the patient experience of EoE. Dysphagia episode frequency is summarized as the total number of dysphagia episodes occurring over each 28-day period following randomization, scaled up to 28 days based on missing days. Requires at least 8 days of evaluable data in each 14-day period within each 28-day period; otherwise the period is set to missing. The number analyzed represents the number of participants with data at that visit.
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Week 24	In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), patients report on whether they experienced episodes of difficulty swallowing in the past 24 hours and if so, how many. Patients respond to 3 questions on the pain, discomfort, and overall severity of the event using a numeric rating scale (0 \[no\] to 10 \[worst\]). This is repeated for each episode reported. Each category score is calculated as the sum of daily average values in the 14-day period divided by the number of days with available episodes of difficulty swallowing episodes during the same 14-day period (each of the three final scores range from 0 to 10, with higher values indicating a worse outcome in that category). Requires at least 8 days of evaluable data during the period; otherwise, the mean scores are set to missing. Days with 0 episodes of difficulty swallowing count as evaluable. In case all 14 days with 0 episode of difficulty swallowing, the score is set to missing.
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24	Week 24	In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), respondents are asked to report the severity of abdominal pain and the severity of nausea at their worst over the past 24 hours using an 11-point numeric rating scale (0 \[no\] to 10 \[worst\]). Abdominal pain severity and nausea severity will be summarized individually as 14-day mean scores. Each 14-day mean score will be calculated as the sum of daily numerical rating scale score responses divided by the number of days with evaluable data in the same 14-day period. Calculation of the 14-day means will require at least 8 out of 14 days of evaluable data; otherwise, the mean score will be set to missing. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52	Week 52	In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), respondents are asked to report the severity of abdominal pain and the severity of nausea at their worst over the past 24 hours using an 11-point numeric rating scale (0 \[no\] to 10 \[worst\]). Abdominal pain severity and nausea severity will be summarized individually as 14-day mean scores. Each 14-day mean score will be calculated as the sum of daily numerical rating scale score responses divided by the number of days with evaluable data in the same 14-day period. Calculation of the 14-day means will require at least 8 out of 14 days of evaluable data; otherwise, the mean score will be set to missing. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Week 24, Week 52	The Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) is an 18-item assessment of EoE symptom severity and frequency validated for use in patients age 8 to 18 years. The recall period is one month. The first 18 questions alternate between a question about a given symptom's frequency (never=0, almost never=1, sometimes=2, often=3, almost always=4) and a question about the symptom's severity (face rating scale with drawings representing: not bad at all=0, a little bad=1, kind of bad=2, bad=3, very bad=4). The remaining two questions ask about frequency of eating less food than others and frequency of needing more time to eat than others. The overall score ranges from 0 to 80, with higher scores representing more severe and frequent EoE symptoms. The number analyzed represents the number of participants with data at that visit.
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Week 24	The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. Responses are on a 5-point scale: Not at all = 4, Slightly = 3, Moderately = 2, Quite a Bit = 1, Extremely = 0. The assessment has 5 domains: eating/diet impact, social impact, emotional impact, disease anxiety and swallowing anxiety. Domain scores are calculated as follows: * Eating/Diet Impact (range 0 to 40): sum of Q2, Q9, Q16, Q24, Q25, Q26, Q27, Q28, Q29, Q30 * Social Impact (range 0 to 16): sum of Q14, Q17, Q19, Q22 * Emotional Impact (range 0 to 32): sum of Q1, Q5, Q6, Q7, Q11, Q13, Q21, Q23 * Disease Anxiety (range 0 to 20): sum of Q4, Q10, Q12, Q15, Q18, * Swallowing Anxiety (range 0 to 12): sum of Q3, Q8, Q20 The total score (range 0 to 120) is calculated as the sum of all responses. Lower scores indicate a greater degree of impairment. Higher scores indicate a better quality of life.
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Week 52	The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. Responses are on a 5-point scale: Not at all = 4, Slightly = 3, Moderately = 2, Quite a Bit = 1, Extremely = 0. The assessment has 5 domains: eating/diet impact, social impact, emotional impact, disease anxiety and swallowing anxiety. Domain scores are calculated as follows: * Eating/Diet Impact (range 0 to 40): sum of Q2, Q9, Q16, Q24, Q25, Q26, Q27, Q28, Q29, Q30 * Social Impact (range 0 to 16): sum of Q14, Q17, Q19, Q22 * Emotional Impact (range 0 to 32): sum of Q1, Q5, Q6, Q7, Q11, Q13, Q21, Q23 * Disease Anxiety (range 0 to 20): sum of Q4, Q10, Q12, Q15, Q18, * Swallowing Anxiety (range 0 to 12): sum of Q3, Q8, Q20 The total score (range 0 to 120) is calculated as the sum of all responses. Lower scores indicate a greater degree of impairment. Higher scores indicate a better quality of life.
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Week 24	The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) were computed from subscale scores to give a broader metric of physical and mental health-related quality of life. All scores range from 0-100, with higher scores meaning better outcomes. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Week 52	The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) were computed from subscale scores to give a broader metric of physical and mental health-related quality of life. All scores range from 0-100, with higher scores meaning better outcomes. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

Other

Measure	Time frame	Description
Safety and Tolerability in Double Blind Period	Up to Week 24	Percentage of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Double Blind treatment period (up to Week 24).
Safety and Tolerability in the Open Label Period	From Week 24 up to Week 52	Percentage of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Open Label treatment period (past week 24).
Benralizumab Pharmacokinetics	Up to week 52	Serum concentrations of benralizumab through Week 52. Geometric mean calculated using log transformed data.
Immunogenicity of Benralizumab in Double Blind + Open Label Periods	Up to Week 52	Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind and Open Label periods.
Immunogenicity of Benralizumab in Double Blind Period	Up to Week 24	Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind period.

Countries

Canada, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Russia, Spain, United Kingdom, United States

Participant flow

Recruitment details

A total of 404 participants were screened between 22SEP2020 and 22FEB2022. Of those, 211 were randomized to either the treatment (104 participants) or placebo (107 participants) arms of the double-blind treatment period. One participant, who did not meet inclusion/exclusion criteria, was incorrectly randomized but not dosed. Therefore, 103 participants started in the treatment arm and 107 in the placebo arm, for a total of 210 participants.

Pre-assignment details

All patients completed a run-in period of 2 to 8 weeks during which inclusion/exclusion criteria was assessed, medical history taken, endoscopy with biopsies performed, and patient reported outcomes (PROs), clinical laboratories, and diet questionnaires were administered.

Participants by arm

Arm	Count
Benralizumab 30mg Benralizumab injection delivered subcutaneously every 4 weeks	103
Placebo Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24	107
Total	210

Withdrawals & dropouts

Period	Reason	FG000	FG001
Double-Blind Treatment Period	Subject perceives the IP to be ineffective.	1	0
Double-Blind Treatment Period	Withdrawal by Subject	1	1
Open-Label Extension Treatment Period	Adverse Event	0	1
Open-Label Extension Treatment Period	Lost to Follow-up	1	0
Open-Label Extension Treatment Period	No study/treatment discontinuation information	0	1
Open-Label Extension Treatment Period	Study terminated by sponsor	44	44
Open-Label Extension Treatment Period	Unable to schedule gastroscopy	0	1
Open-Label Extension Treatment Period	Withdrawal by Subject	0	1
Open-Label Treatment Period	Lost to Follow-up	0	1
Open-Label Treatment Period	Study terminated by sponsor	17	19
Open-Label Treatment Period	Withdrawal by Subject	4	3

Baseline characteristics

Characteristic	Total	Benralizumab	Placebo
Age, Continuous	33.7 years STANDARD_DEVIATION 13.08	33.9 years STANDARD_DEVIATION 13.49	33.6 years STANDARD_DEVIATION 12.73
Age, Customized 18-21 years old	22 Participants	11 Participants	11 Participants
Age, Customized < 18 years old	28 Participants	14 Participants	14 Participants
Age, Customized <= 21 years old	50 Participants	25 Participants	25 Participants
Age, Customized > 21 years old	160 Participants	78 Participants	82 Participants
Age, Customized 22-35 years old	67 Participants	32 Participants	35 Participants
Age, Customized >= 36 years old	93 Participants	46 Participants	47 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	7 Participants	2 Participants	5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 Participants	6 Participants	10 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	191 Participants	97 Participants	94 Participants
Race/Ethnicity, Customized Other	4 Participants	3 Participants	1 Participants
Race/Ethnicity, Customized White	193 Participants	97 Participants	96 Participants
Sex: Female, Male Female	53 Participants	31 Participants	22 Participants
Sex: Female, Male Male	157 Participants	72 Participants	85 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 103	0 / 107	0 / 208
other Total, other adverse events	60 / 103	42 / 107	95 / 208
serious Total, serious adverse events	4 / 103	1 / 107	9 / 208

Outcome results

Primary

Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)

The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing. The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)	Week 24	-12.102 Score
Benralizumab	Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)	Week 52	-19.409 Score
Placebo	Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)	Week 24	-15.101 Score
Placebo	Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)	Week 52	-19.806 Score

Comparison: Analysis completed at Week 24.p-value: 0.17795% CI: [-1.36, 7.35]ANCOVA

Primary

Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.

Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count \<= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders. The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (NUMBER)
Benralizumab	Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.	Week 24	87.4 Percentage of Participants
Benralizumab	Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.	Week 52	82.6 Percentage of Participants
Placebo	Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.	Week 24	6.5 Percentage of Participants
Placebo	Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.	Week 52	89.4 Percentage of Participants

Comparison: Analysis completed at Week 24.p-value: <0.000195% CI: [38.17, 361.64]Cochran-Mantel-Haenszel

Secondary

Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24

Esophagogastroduodenoscopy biopsies were collected at week 24 and sent to the central lab for slide preparation and for central, blinded pathology review of tissue eosinophil counts and histopathology. Centralized slide assessments and scoring from an independent physician review was performed for all biopsies.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	1 to <=6 eos/hpf	6 Participants
Benralizumab	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	15 to <60 eos/hpf	0 Participants
Benralizumab	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	7 to <15 eos/hpf	2 Participants
Benralizumab	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	>=60 eos/hpf	2 Participants
Benralizumab	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	<1 eos/hpf	84 Participants
Placebo	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	>=60 eos/hpf	56 Participants
Placebo	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	<1 eos/hpf	0 Participants
Placebo	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	1 to <=6 eos/hpf	7 Participants
Placebo	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	7 to <15 eos/hpf	3 Participants
Placebo	Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24	15 to <60 eos/hpf	33 Participants

Secondary

Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24

EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total grade score (TGS): mean of the grade score ratios per region. Grade score ratio per region is the sum of all available feature grade scores divided by the maximum possible score. The maximum possible total grade score is 1. The number analyzed represents the number of participants with data at that visit (including imputed values).

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Benralizumab	Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24	-0.264 Grade Score Ratio Change
Placebo	Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24	-0.089 Grade Score Ratio Change

p-value: <0.000195% CI: [-0.21, -0.14]ANCOVA

Secondary

Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24

EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total stage score (TSS): mean of the stage score ratios per region. Stage score ratio per region is the sum of all available feature stage scores divided by the maximum possible score. The maximum possible total stage score is 1. The number analyzed represents the number of participants with data at that visit (including imputed values).

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Benralizumab	Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24	-0.199 Grade Score Ratio Change
Placebo	Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24	-0.077 Grade Score Ratio Change

p-value: <0.000195% CI: [-0.16, -0.09]ANCOVA

Secondary

Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24

The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) were computed from subscale scores to give a broader metric of physical and mental health-related quality of life. All scores range from 0-100, with higher scores meaning better outcomes. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Physical functioning (PF)	0.2 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Role limitations due to physical health (RP)	0.5 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Bodily pain (BP)	-0.6 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	General health perceptions (GH)	-0.9 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Vitality (VT)	-0.5 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Social functioning (SF)	-1.5 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Role limitations due to emotional problems (RE)	-1.1 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Mental health (MH)	-1.7 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Psychometrically-based physical summary score (PCS)	0.4 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Mental health component summary scores (MCS)	-1.8 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Mental health (MH)	-0.8 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Physical functioning (PF)	0.5 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Social functioning (SF)	0.1 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Role limitations due to physical health (RP)	1.5 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Mental health component summary scores (MCS)	-1.2 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Bodily pain (BP)	0.2 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Role limitations due to emotional problems (RE)	-0.4 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	General health perceptions (GH)	-0.9 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Psychometrically-based physical summary score (PCS)	0.8 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24	Vitality (VT)	-0.5 Score

Comparison: Physical functioning (PF)p-value: 0.685295% CI: [-1.93, 1.27]ANCOVA

Comparison: Role limitations due to physical health (RP)p-value: 0.268595% CI: [-2.57, 0.72]ANCOVA

Comparison: Bodily pain (BP)p-value: 0.53895% CI: [-3.27, 1.71]ANCOVA

Comparison: General health perceptions (GH)p-value: 0.973495% CI: [-1.81, 1.75]ANCOVA

Comparison: Vitality (VT)p-value: 0.965395% CI: [-2.09, 2.19]ANCOVA

Comparison: Social functioning (SF)p-value: 0.232695% CI: [-4.04, 0.98]ANCOVA

Comparison: Role limitations due to emotional problems (RE)p-value: 0.627495% CI: [-3.44, 2.08]ANCOVA

Comparison: Mental health (MH)p-value: 0.459995% CI: [-3.14, 1.42]ANCOVA

Comparison: Psychometrically-based physical summary score (PCS)p-value: 0.645695% CI: [-2.07, 1.28]ANCOVA

Comparison: Mental health component summary scores (MCS)p-value: 0.620695% CI: [-3.08, 1.84]ANCOVA

Secondary

Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Physical functioning (PF)	0.3 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Role limitations due to physical health (RP)	-0.5 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Bodily pain (BP)	0.6 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	General health perceptions (GH)	2.3 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Vitality (VT)	-0.2 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Social functioning (SF)	0.2 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Role limitations due to emotional problems (RE)	-0.1 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Mental health (MH)	1.2 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Psychometrically-based physical summary score (PCS)	0.5 Score
Benralizumab	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Mental health component summary scores (MCS)	0.5 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Mental health (MH)	-1.1 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Physical functioning (PF)	0.4 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Social functioning (SF)	-0.5 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Role limitations due to physical health (RP)	0.9 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Mental health component summary scores (MCS)	-1.9 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Bodily pain (BP)	1.8 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Role limitations due to emotional problems (RE)	-0.3 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	General health perceptions (GH)	0.7 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Psychometrically-based physical summary score (PCS)	1.4 Score
Placebo	Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52	Vitality (VT)	-2.0 Score

Secondary

Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24

In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), respondents are asked to report the severity of abdominal pain and the severity of nausea at their worst over the past 24 hours using an 11-point numeric rating scale (0 \[no\] to 10 \[worst\]). Abdominal pain severity and nausea severity will be summarized individually as 14-day mean scores. Each 14-day mean score will be calculated as the sum of daily numerical rating scale score responses divided by the number of days with evaluable data in the same 14-day period. Calculation of the 14-day means will require at least 8 out of 14 days of evaluable data; otherwise, the mean score will be set to missing. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24	Abdominal pain severity	-0.549 Scores per day
Benralizumab	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24	Nausea severity	-0.524 Scores per day
Placebo	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24	Abdominal pain severity	-0.815 Scores per day
Placebo	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24	Nausea severity	-0.820 Scores per day

Comparison: Abdominal pain severityp-value: 0.224895% CI: [-0.16, 0.7]ANCOVA

Comparison: Nausea severity.p-value: 0.157595% CI: [-0.11, 0.71]ANCOVA

Secondary

Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52	Abdominal pain severity	-0.826 Scores per day
Benralizumab	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52	Nausea severity	-0.855 Scores per day
Placebo	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52	Abdominal pain severity	-1.039 Scores per day
Placebo	Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52	Nausea severity	-0.960 Scores per day

Secondary

Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24

The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. Responses are on a 5-point scale: Not at all = 4, Slightly = 3, Moderately = 2, Quite a Bit = 1, Extremely = 0. The assessment has 5 domains: eating/diet impact, social impact, emotional impact, disease anxiety and swallowing anxiety. Domain scores are calculated as follows: * Eating/Diet Impact (range 0 to 40): sum of Q2, Q9, Q16, Q24, Q25, Q26, Q27, Q28, Q29, Q30 * Social Impact (range 0 to 16): sum of Q14, Q17, Q19, Q22 * Emotional Impact (range 0 to 32): sum of Q1, Q5, Q6, Q7, Q11, Q13, Q21, Q23 * Disease Anxiety (range 0 to 20): sum of Q4, Q10, Q12, Q15, Q18, * Swallowing Anxiety (range 0 to 12): sum of Q3, Q8, Q20 The total score (range 0 to 120) is calculated as the sum of all responses. Lower scores indicate a greater degree of impairment. Higher scores indicate a better quality of life.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Eating/Diet Impact	1.370 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Social Impact	1.095 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Emotional Impact	0.912 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Disease Anxiety	0.185 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Swallowing Anxiety	0.443 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Total Score	4.380 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Swallowing Anxiety	0.605 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Eating/Diet Impact	1.169 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Disease Anxiety	-0.201 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Social Impact	0.948 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Total Score	3.362 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24	Emotional Impact	0.902 Score

Comparison: Eating/Diet Impactp-value: 0.823995% CI: [-1.57, 1.98]ANCOVA

Comparison: Social Impactp-value: 0.762395% CI: [-0.8, 1.1]ANCOVA

Comparison: Emotional Impactp-value: 0.989895% CI: [-1.47, 1.49]ANCOVA

Comparison: Disease Anxietyp-value: 0.460395% CI: [-0.64, 1.41]ANCOVA

Comparison: Swallowing Anxietyp-value: 0.661395% CI: [-0.89, 0.56]ANCOVA

Comparison: Total Scorep-value: 0.696595% CI: [-4.09, 6.13]ANCOVA

Secondary

Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Eating/Diet Impact	1.408 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Social Impact	1.462 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Emotional Impact	1.768 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Disease Anxiety	1.063 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Swallowing Anxiety	0.677 Score
Benralizumab	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Total Score	6.749 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Swallowing Anxiety	1.085 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Eating/Diet Impact	1.949 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Disease Anxiety	1.152 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Social Impact	1.984 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Total Score	8.714 Score
Placebo	Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52	Emotional Impact	2.451 Score

Secondary

Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)

EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EoE.The score ranges from 0 (normal) to 9 (severe disease). EREFS total score (TS): The worst score for each individual component from the proximal and distal scores were summed to form the EREFS total score (TS). The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)	Week 24	-0.5 Score
Benralizumab	Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)	Week 52	-0.3 Score
Placebo	Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)	Week 24	-0.4 Score
Placebo	Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)	Week 52	-0.7 Score

Comparison: Analysis completed at Week 24.p-value: 0.732295% CI: [-0.52, 0.32]ANCOVA

Secondary

Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), patients report on whether they experienced episodes of difficulty swallowing in the past 24 hours and if so, how many. Patients respond to 3 questions on the pain, discomfort, and overall severity of the event using a numeric rating scale (0 \[no\] to 10 \[worst\]). This is repeated for each episode reported. Each category score is calculated as the sum of daily average values in the 14-day period divided by the number of days with available episodes of difficulty swallowing episodes during the same 14-day period (each of the three final scores range from 0 to 10, with higher values indicating a worse outcome in that category). Requires at least 8 days of evaluable data during the period; otherwise, the mean scores are set to missing. Days with 0 episodes of difficulty swallowing count as evaluable. In case all 14 days with 0 episode of difficulty swallowing, the score is set to missing.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Dysphagia-related pain	-0.452 Scores per day
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Dysphagia-related discomfort	-0.370 Scores per day
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Overall episode severity	-0.481 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Dysphagia-related pain	-0.412 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Dysphagia-related discomfort	-0.189 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24	Overall episode severity	-0.137 Scores per day

Comparison: Dysphagia-related pain.p-value: 0.865695% CI: [-0.5, 0.42]ANCOVA

Comparison: Dysphagia-related discomfort.p-value: 0.392695% CI: [-0.6, 0.23]ANCOVA

Comparison: Overall episode severity.p-value: 0.086795% CI: [-0.74, 0.05]ANCOVA

Secondary

Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Dysphagia-related pain	-0.511 Scores per day
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Dysphagia-related discomfort	-0.456 Scores per day
Benralizumab	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Overall episode severity	-0.522 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Dysphagia-related pain	-0.776 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Dysphagia-related discomfort	-0.625 Scores per day
Placebo	Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52	Overall episode severity	-0.732 Scores per day

Secondary

Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)

The Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) is an 18-item assessment of EoE symptom severity and frequency validated for use in patients age 8 to 18 years. The recall period is one month. The first 18 questions alternate between a question about a given symptom's frequency (never=0, almost never=1, sometimes=2, often=3, almost always=4) and a question about the symptom's severity (face rating scale with drawings representing: not bad at all=0, a little bad=1, kind of bad=2, bad=3, very bad=4). The remaining two questions ask about frequency of eating less food than others and frequency of needing more time to eat than others. The overall score ranges from 0 to 80, with higher scores representing more severe and frequent EoE symptoms. The number analyzed represents the number of participants with data at that visit.

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (MEAN)	Dispersion
Benralizumab	Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Week 24	-0.8 Score	Standard Deviation 11.69
Benralizumab	Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Week 52	-6.5 Score	Standard Deviation 18.04
Placebo	Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Week 24	-5.9 Score	Standard Deviation 14.24
Placebo	Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Week 52	-12.5 Score	Standard Deviation 15.67

Secondary

Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)

Dysphagia free days is a count ranging from 0-28. Higher counts indicate better outcomes. The number analyzed represents the number of participants with data at that visit.

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (MEAN)	Dispersion
Benralizumab	Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)	Week 24	12.65 Days	Standard Deviation 10.589
Benralizumab	Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)	Week 52	19.33 Days	Standard Deviation 10.95
Placebo	Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)	Week 24	16.32 Days	Standard Deviation 11.286
Placebo	Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)	Week 52	20.80 Days	Standard Deviation 10.472

Secondary

Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)

EoE-3D is a daily diary focused on the patient experience of EoE. Dysphagia episode frequency is summarized as the total number of dysphagia episodes occurring over each 28-day period following randomization, scaled up to 28 days based on missing days. Requires at least 8 days of evaluable data in each 14-day period within each 28-day period; otherwise the period is set to missing. The number analyzed represents the number of participants with data at that visit.

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (MEAN)	Dispersion
Benralizumab	Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)	Week 24	20.3 Ratio of Episodes per 28 Day period	Standard Deviation 28.05
Benralizumab	Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)	Week 52	6.8 Ratio of Episodes per 28 Day period	Standard Deviation 11.59
Placebo	Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)	Week 24	13.8 Ratio of Episodes per 28 Day period	Standard Deviation 19.15
Placebo	Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)	Week 52	6.2 Ratio of Episodes per 28 Day period	Standard Deviation 9.83

Secondary

Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24

Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are much better, moderately better, a little better, about the same/no change, a little worse, moderately worse, and much worse. The number analyzed represents the participants with evaluable PGI-C results at that timepoint.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	A little better	21 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	A little worse	7 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Moderately better	13 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Moderately worse	3 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	About the same	37 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Much worse	2 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Much better	13 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Much worse	1 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Much better	13 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Moderately better	17 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	A little better	20 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	About the same	36 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	A little worse	6 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24	Moderately worse	3 Participants

Secondary

Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	A little better	8 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	A little worse	4 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Moderately better	3 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Moderately worse	0 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	About the same	9 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Much worse	0 Participants
Benralizumab	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Much better	12 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Much worse	0 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Much better	13 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Moderately better	12 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	A little better	12 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	About the same	6 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	A little worse	0 Participants
Placebo	Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52	Moderately worse	0 Participants

Secondary

Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24

Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are no symptoms, very mild, mild, moderate, severe, and very severe. The number analyzed represents the participants with evaluable PGI-S results at that timepoint.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	No symptoms	4 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Very mild	23 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Mild	34 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Moderate	29 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Severe	3 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Very Severe	3 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Severe	6 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	No symptoms	11 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Moderate	17 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Very mild	27 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Very Severe	2 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24	Mild	32 Participants

Secondary

Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52

Time frame: Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	No symptoms	6 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Very mild	12 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Mild	9 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Moderate	8 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Severe	0 Participants
Benralizumab	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Very Severe	1 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Severe	0 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	No symptoms	10 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Moderate	5 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Very mild	14 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Very Severe	0 Participants
Placebo	Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52	Mild	13 Participants

Secondary

Percent Change From Baseline in Tissue Eosinophils

Percent change from baseline in tissue eosinophils (eos) at Week 24 and Week 52. The number analyzed represents the number of participants with data at that visit (including imputed values).

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Benralizumab	Percent Change From Baseline in Tissue Eosinophils	Week 24	-94.8 Percentage of change
Benralizumab	Percent Change From Baseline in Tissue Eosinophils	Week 52	-85.0 Percentage of change
Placebo	Percent Change From Baseline in Tissue Eosinophils	Week 24	1.4 Percentage of change
Placebo	Percent Change From Baseline in Tissue Eosinophils	Week 52	-88.6 Percentage of change

Comparison: Analysis completed at Week 24.p-value: <0.000195% CI: [-114.53, -77.85]ANCOVA

Secondary

Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.

Percent of patients with any relevant concomitant procedures or healthcare resource utilization for Eosinophilic esophagitis (EoE) or an EoE-related episode (e.g., an intervention for food impaction or stricture requiring dilatation) since last healthcare resource utilization assessment during the previous scheduled visit. Assessed at Week 24 and Week 52.

Time frame: Week 24, Week 52

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.	Week 24	3 Participants
Benralizumab	Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.	Week 52	0 Participants
Placebo	Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.	Week 24	5 Participants
Placebo	Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.	Week 52	2 Participants

Secondary

Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24

Percentage of participants with a treatment response at Week 24. A treatment response is defined as composite of histologic response and clinically meaningful improvement (30% reduction) from baseline in DSQ score. Participants with missing data at Week 24 or with intercurrent events prior to Week 24 are considered non-responders.

Time frame: Week 24

Population: Full analysis set (All randomized participants who received at least one dose of IP).

Arm	Measure	Value (NUMBER)
Benralizumab	Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24	43.7 Percentage of Participants
Placebo	Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24	4.7 Percentage of Participants

p-value: <0.000195% CI: [5.79, 43.47]Cochran-Mantel-Haenszel

Other Pre-specified

Benralizumab Pharmacokinetics

Serum concentrations of benralizumab through Week 52. Geometric mean calculated using log transformed data.

Time frame: Up to week 52

Population: PK analysis set (All participants who received benralizumab and who had at least one quantifiable serum PK observation post first dose).

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Benralizumab	Benralizumab Pharmacokinetics	Week 8	1555.70 ng/mL
Benralizumab	Benralizumab Pharmacokinetics	Week 16	1582.46 ng/mL
Benralizumab	Benralizumab Pharmacokinetics	Week 24	1338.65 ng/mL
Benralizumab	Benralizumab Pharmacokinetics	Week 36	1405.94 ng/mL
Benralizumab	Benralizumab Pharmacokinetics	Week 52	1278.13 ng/mL
Placebo	Benralizumab Pharmacokinetics	Week 36	1362.27 ng/mL
Placebo	Benralizumab Pharmacokinetics	Week 24	NA ng/mL
Placebo	Benralizumab Pharmacokinetics	Week 52	1495.61 ng/mL

Other Pre-specified

Immunogenicity of Benralizumab in Double Blind + Open Label Periods

Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind and Open Label periods.

Time frame: Up to Week 52

Population: Safety analysis set (All participants who received at least one dose of IP).

Arm	Measure	Group	Value (NUMBER)
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	Treatment-emergent ADA positive/ADA incidence	19 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA positive subjects with maximum titre > median of maximum titres	7 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA negative (negative at all assessments)	84 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	nAb positive/nAb prevalence	10 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA persistently positive	16 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA persistently positive and nAb positive	10 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA positive/ADA prevalence (positive at baseline and/or post-baseline)	19 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA persistently positive and nAb positive	5 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA positive/ADA prevalence (positive at baseline and/or post-baseline)	17 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA negative (negative at all assessments)	88 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	Treatment-emergent ADA positive/ADA incidence	11 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA persistently positive	10 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	ADA positive subjects with maximum titre > median of maximum titres	7 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind + Open Label Periods	nAb positive/nAb prevalence	5 Participants

Other Pre-specified

Immunogenicity of Benralizumab in Double Blind Period

Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind period.

Time frame: Up to Week 24

Population: Safety analysis set (All participants who received at least one dose of IP).

Arm	Measure	Group	Value (NUMBER)
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	ADA persistently positive and nAb positive	10 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	ADA persistently positive	18 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	ADA negative (negative at all assessments)	85 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	ADA positive subjects with maximum titre > median of maximum titres	6 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	ADA positive/ADA prevalence (positive at baseline and/or post-baseline)	18 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	nAb positive/nAb prevalence	10 Participants
Benralizumab	Immunogenicity of Benralizumab in Double Blind Period	Treatment-emergent ADA positive/ADA incidence	18 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	nAb positive/nAb prevalence	0 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	ADA positive/ADA prevalence (positive at baseline and/or post-baseline)	8 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	ADA negative (negative at all assessments)	99 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	Treatment-emergent ADA positive/ADA incidence	4 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	ADA persistently positive	3 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	ADA positive subjects with maximum titre > median of maximum titres	4 Participants
Placebo	Immunogenicity of Benralizumab in Double Blind Period	ADA persistently positive and nAb positive	0 Participants

Other Pre-specified

Safety and Tolerability in Double Blind Period

Percentage of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Double Blind treatment period (up to Week 24).

Time frame: Up to Week 24

Population: Safety analysis set (All participants who received at least one dose of IP).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Safety and Tolerability in Double Blind Period	Any AE	66 Participants
Benralizumab	Safety and Tolerability in Double Blind Period	Any SAE	2 Participants
Placebo	Safety and Tolerability in Double Blind Period	Any AE	66 Participants
Placebo	Safety and Tolerability in Double Blind Period	Any SAE	1 Participants

Other Pre-specified

Safety and Tolerability in the Open Label Period

Percentage of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Open Label treatment period (past week 24).

Time frame: From Week 24 up to Week 52

Population: Safety analysis set (All participants who received at least one dose of IP).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Benralizumab	Safety and Tolerability in the Open Label Period	Any AE	53 Participants
Benralizumab	Safety and Tolerability in the Open Label Period	Any SAE	2 Participants
Placebo	Safety and Tolerability in the Open Label Period	Any AE	60 Participants
Placebo	Safety and Tolerability in the Open Label Period	Any SAE	4 Participants

Source: ClinicalTrials.gov · Data processed: Feb 6, 2026

A Study of Benralizumab in Patients With Eosinophilic Esophagitis

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)

Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.

Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24

Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24

Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24

Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24

Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52

Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24

Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52

Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24

Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52

Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)

Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)

Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)

Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)

Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24

Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52

Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24

Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52

Percent Change From Baseline in Tissue Eosinophils

Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.

Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24

Benralizumab Pharmacokinetics

Immunogenicity of Benralizumab in Double Blind + Open Label Periods

Immunogenicity of Benralizumab in Double Blind Period

Safety and Tolerability in Double Blind Period

Safety and Tolerability in the Open Label Period