Trial Outcomes & Findings for A Study of Benralizumab in Patients With Eosinophilic Esophagitis (NCT NCT04543409)

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.

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.

Race and ethnicity are missing for all French participants due to local regulation rules.

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.

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).

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).

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).

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).

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).

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.

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 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.

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.

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.

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.

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).

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).

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.

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.

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.

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).

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).

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 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 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 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 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.

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

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

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

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

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