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Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis (MESSINA)

Summary
EudraCT number	2019-002871-32
Trial protocol	ES NL PL DE GB FR IT
Global end of trial date	06 Feb 2023

Results information
Results version number	v1(current)
This version publication date	20 Jul 2023
First version publication date	20 Jul 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

D3255C00001

ISRCTN number

US NCT number

NCT04543409

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca

Sponsor organisation address

151 85, Södertälje, Sweden,

Public contact

Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com

Scientific contact

Global Clinical Lead, AstraZeneca, +1 8772409479, information.center@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001214-PIP05-19

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

06 Feb 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Feb 2023

Was the trial ended prematurely?

Yes

Main objective of the trial

The purpose of this study is to evaluate the effect of a 30 mg dosing regimen of benralizumab every four weeks on histologic signs and symptoms of Eosinophilic Esophagitis in patients with symptomatic and histologically active Eosinophilic Esophagitis

Protection of trial subjects

The independent data monitoring committee (IDMC), consisting of 2 clinicians (including at least 1 EoE expert) and a statistician, was used for this study. They had the responsibility of evaluating cumulative safety and other clinical trial data at regular intervals and made appropriate recommendations based on the available data. The IDMC functioned independently of all other individuals associated with the conduct of the studies, including the study sponsor, AstraZeneca. The committee operated in accordance with a IDMC charter.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Sep 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 70

Country: Number of subjects enrolled

Canada: 20

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Israel: 15

Country: Number of subjects enrolled

Italy: 12

Country: Number of subjects enrolled

Japan: 6

Country: Number of subjects enrolled

Netherlands: 9

Country: Number of subjects enrolled

Poland: 12

Country: Number of subjects enrolled

Russian Federation: 12

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

United Kingdom: 11

Worldwide total number of subjects

210

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

179

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

404 patients were screened from 22SEP2020-22FEB2022. 211 were randomized to the treatment (104) or placebo (107) arms of the double-blind period. 1 patient, who did not meet inclusion/exclusion criteria, was incorrectly randomized but not dosed. Therefore, 103 patients started in the treatment arm and 107 in the placebo arm, for a total of 210.

Screening 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.

Period 1 title

Double-Blind treatment period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Carer, Data analyst, Subject, Assessor

Are arms mutually exclusive

Yes

Benralizumab

Arm description

30mg Benralizumab injection delivered subcutaneously every 4 weeks through week 24

Arm type

Experimental

Investigational medicinal product name

Benralizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/mL solution for injection in accessorized prefilled syringe, 1 mL fill volume

Placebo

Arm description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Matching placebo solution for injection in accessorized prefilled syringe, 1 mL fill volume

Number of subjects in period 1	Benralizumab	Placebo
Started	103	107
Completed	101	106
Not completed	2	1
Consent withdrawn by subject	1	1
Subject perceives the IP to be ineffective.	1	-

Period 2 title

Open-Label Treatment Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Benralizumab

Arm description

30mg Benralizumab injection delivered subcutaneously every 4 weeks

Arm type

Experimental

Investigational medicinal product name

Benralizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/mL solution for injection in accessorized prefilled syringe, 1 mL fill volume

Placebo

Arm description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24

Arm type

Placebo

Investigational medicinal product name

Benralizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe, Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/mL solution for injection in accessorized prefilled syringe, 1 mL fill volume

Number of subjects in period 2 ^[1]	Benralizumab	Placebo
Started	100	105
Completed	79	82
Not completed	21	23
Consent withdrawn by subject	4	3
Study terminated by sponsor	17	19
Lost to follow-up	-	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: One participant enrolled in OL treatment period off study drug (not included in this count) for the treatment group. One participant chose not to enroll in the OL treatment period for the placebo group.

Period 3 title

Open-Label Extension Treatment Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Benralizumab

Arm description

30mg Benralizumab injection delivered subcutaneously every 4 weeks

Arm type

Experimental

Investigational medicinal product name

Benralizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/mL solution for injection in accessorized prefilled syringe, 1 mL fill volume

Placebo

Arm description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24

Arm type

Placebo

Investigational medicinal product name

Benralizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/mL solution for injection in accessorized prefilled syringe, 1 mL fill volume

Number of subjects in period 3 ^[2]	Benralizumab	Placebo
Started	45	48
Completed	0	0
Not completed	45	48
Consent withdrawn by subject	-	1
Adverse event, non-fatal	-	1
Study terminated by sponsor	44	44
No study/treatment discontinuation information	-	1
Lost to follow-up	1	-
Unable to schedule gastroscopy	-	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 34 participants in each treatment arm from previous period chose not to enroll in optional OLE period.

Baseline characteristics

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Reporting group title

Benralizumab

Reporting group description

30mg Benralizumab injection delivered subcutaneously every 4 weeks through week 24

Reporting group title

Placebo

Reporting group description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24

Reporting group values	Benralizumab	Placebo	Total
Number of subjects	103	107	210
Age Categorical
Age Group 1
Units: Participants
< 18 years old	14	14	28
18-21 years old	11	11	22
22-35 years old	32	35	67
>= 36 years old	46	47	93
Age Continuous
Units: years
arithmetic mean (standard deviation)	33.9 ( 13.49 )	33.6 ( 12.73 )	-
Sex: Female, Male
Units: Participants
Female	31	22	53
Male	72	85	157
Age, Customized
Age Group 3
Units: Subjects
<= 21 years old	25	25	50
> 21 years old	78	82	160

End points

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Reporting group title

Benralizumab

Reporting group description

30mg Benralizumab injection delivered subcutaneously every 4 weeks through week 24

Reporting group title

Placebo

Reporting group description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24

Reporting group title

Benralizumab

Reporting group description

30mg Benralizumab injection delivered subcutaneously every 4 weeks

Reporting group title

Placebo

Reporting group description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24

Reporting group title

Benralizumab

Reporting group description

30mg Benralizumab injection delivered subcutaneously every 4 weeks

Reporting group title

Placebo

Reporting group description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24

Primary: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 24.

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End point title

Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 24.

End point description

Proportion of patients with a histologic response at Week 24. A histologic response is defined as a peak esophageal intraepithelial eosinophil count <= 6 eos/hpf across all available esophageal levels. 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.

End point type

Primary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Percentage of Participants
number (confidence interval 95%)
Week 24	87.4 (80.97 to 93.79)	6.5 (1.86 to 11.23)

Cochran-Mantel Haenszel (CMH) Test

Statistical analysis description

Analysis completed at Week 24.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

117.49

Confidence interval

level

95%

sides

2-sided

lower limit

38.17

upper limit

361.64

Notes
[1] - 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.
[2] - P value was <0.0001

Primary: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 24

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End point title

Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 24

End point description

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).

End point type

Primary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	95	100
Units: Score
least squares mean (confidence interval 95%)
Week 24	-12.102 (-16.05 to -8.15)	-15.101 (-19.02 to -11.19)

ANCOVA model analysis

Statistical analysis description

Model: Change from baseline in DSQ = Treatment + baseline DSQ + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.177

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

2.999

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

7.35

Notes
[3] - For any patients with intercurrent events, the DSQ scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.

Secondary: Percent change from baseline in tissue eosinophils at Week 24

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End point title

Percent change from baseline in tissue eosinophils at Week 24

End point description

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

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	97	100
Units: Percent
least squares mean (confidence interval 95%)
Week 24	-94.8 (-100.00 to -82.45)	1.4 (-11.75 to 14.60)

ANCOVA model analysis

Statistical analysis description

Model: Percent change from baseline in Peak Esophageal intraepithelial eosinophil counts = Treatment + baseline Peak Esophageal intraepithelial eosinophil counts.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.0001 ^[5]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-96.2

Confidence interval

level

95%

sides

2-sided

lower limit

-114.53

upper limit

-77.85

Notes
[4] - For any patients with intercurrent events, the Peak Esophageal intraepithelial eosinophil (eos) counts after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).
[5] - P-value was <0.0001

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total grade score at Week 24

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End point title

Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total grade score at Week 24

End point description

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).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	97	100
Units: Score
least squares mean (confidence interval 95%)	-0.264 (-0.297 to -0.232)	-0.089 (-0.122 to -0.056)

ANCOVA model analysis

Statistical analysis description

Model: Change from baseline in EoE-HSS total grade score = Treatment + baseline EoE-HSS grade score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.0001 ^[7]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.175

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

-0.14

Notes
[6] - For any patients with intercurrent events, the EoE-HSS total grade score after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).
[7] - P-value was <0.0001

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total stage score at Week 24

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End point title

Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total stage score at Week 24

End point description

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).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	97	100
Units: Score
least squares mean (confidence interval 95%)	-0.199 (-0.228 to -0.169)	-0.077 (-0.107 to -0.046)

ANCOVA model analysis

Statistical analysis description

Model: Change from baseline in EoE-HSS total stage score = Treatment + baseline EoE-HSS stage score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.0001 ^[9]

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.122

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

-0.09

Notes
[8] - For any patients with intercurrent events, the EoE-HSS total stage score after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).
[9] - P-value was <0.0001

Secondary: Changes from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 24

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End point title

Changes from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 24

End point description

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).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	85	84
Units: Score
least squares mean (confidence interval 95%)	-0.5 (-0.91 to -0.10)	-0.4 (-0.85 to -0.01)

ANCOVA model analysis

Statistical analysis description

Model: Change from baseline in EREFS total score = Treatment + baseline EREFS total score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.7322

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

0.32

Notes
[10] - For any patients with intercurrent events, the centrally-read EREFS total score after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Secondary: Treatment responder rate, 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

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End point title

Treatment responder rate, 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

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Percentage of Participants
number (confidence interval 95%)	43.7 (34.11 to 53.27)	4.7 (0.67 to 8.67)

Cochran-Mantel Haenszel (CMH) test

Statistical analysis description

Controlling for region (North America and Rest of the world), baseline steroid use, and presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

15.86

Confidence interval

level

95%

sides

2-sided

lower limit

5.79

upper limit

43.47

Notes
[11] - P-value was <0.0001

Secondary: Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24

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End point title

Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24

End point description

Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Participants
<1 eos/hpf	84	0
1 to <=6 eos/hpf	6	7
7 to <15 eos/hpf	2	3
15 to <60 eos/hpf	0	33
>=60 eos/hpf	2	56

No statistical analyses for this end point

Secondary: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 24

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End point title

Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	89	93
Units: Days
arithmetic mean (standard deviation)
Week 24	12.65 ( 10.589 )	16.32 ( 11.286 )

No statistical analyses for this end point

Secondary: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

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End point title

Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	89	94
Units: Days
arithmetic mean (standard deviation)
Week 24	20.3 ( 28.05 )	13.8 ( 19.15 )

No statistical analyses for this end point

Secondary: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24

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End point title

Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24

End point description

EoE-3D is a daily diary focused on the patient experience of EoE. The dysphagia-related pain, discomfort and overall episode severity are 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. Requires at least 8 days of evaluable data during the period; otherwise the mean scores are set to missing. Days with 0 episode of difficulty swallowing count as evaluable even there is no severity collected. In case all 14 days with 0 episode of difficulty swallowing, the score would be set as missing. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	84	73
Units: Score
least squares mean (confidence interval 95%)
Dysphagia-related pain	-0.452 (-0.86 to -0.05)	-0.412 (-0.84 to 0.02)
Dysphagia-related discomfort	-0.370 (-0.73 to -0.01)	-0.189 (-0.57 to 0.19)
Overall episode severity	-0.481 (-0.83 to -0.13)	-0.137 (-0.51 to 0.24)

ANCOVA model analysis for dysphagia-related pain

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.8656

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.42

Notes
[12] - For any patients with intercurrent events, the EoE-3D scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis for overall episode severity

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

= 0.0867

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.344

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

0.05

Notes
[13] - For any patients with intercurrent events, the EoE-3D scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA analysis for dysphagia-related discomfort

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

157

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.3926

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.181

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.23

Notes
[14] - For any patients with intercurrent events, the EoE-3D scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Secondary: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24

Top of page

End point title

Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24

End point description

Abdominal pain severity and nausea severity were summarized individually as 14-day means scores. Requires at least 8 days of evaluable data. Otherwise the mean score is set to missing. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	95	101
Units: Score
least squares mean (confidence interval 95%)
Abdominal pain severity	-0.549 (-0.94 to -0.16)	-0.815 (-1.20 to -0.53)
Nausea severity	-0.524 (-0.90 to -0.15)	-0.820 (-1.19 to -0.45)

ANCOVA model analysis for nausea severity

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.1575

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.296

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.71

Notes
[15] - For any patients with intercurrent events, the EoE-3D scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA analysis for abdominal pain severity

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

= 0.2248

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.267

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.7

Notes
[16] - For any patients with intercurrent events, the EoE-3D scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Secondary: Changes from baseline in PEESS at Week 24

Top of page

End point title

Changes from baseline in PEESS at Week 24

End point description

The Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) is a questionnaire of EoE symptom severity and frequency in patients age 8 to 18 years. The number analyzed represents the number of participants with data at that visit.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	12	9
Units: Score
arithmetic mean (standard deviation)
Week 24	-0.8 ( 11.69 )	-5.9 ( 14.24 )

No statistical analyses for this end point

Secondary: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24

Top of page

End point title

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

End point description

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. The overall score ranges from 0 to 96, with higher scores meaning better quality of life. Total Score: sum of Eating/Diet, Social Impact, Emotional Impact, Disease Anxiety and Swallow Anxiety domain scores. The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	96	96
Units: Score
least squares mean (confidence interval 95%)
Eating/Diet Impact	1.370 (-0.27 to 3.01)	1.169 (-0.46 to 2.79)
Social Impact	1.095 (0.21 to 1.98)	0.948 (0.07 to 1.83)
Emotional Impact	0.912 (-0.46 to 2.29)	0.902 (-0.46 to 2.27)
Disease Anxiety	0.185 (-0.77 to 1.14)	-0.201 (-1.15 to 0.75)
Swallowing Anxiety	0.443 (-0.23 to 1.12)	0.605 (-0.06 to 1.27)
Total Score	4.380 (-0.36 to 9.12)	3.362 (-1.33 to 8.06)

ANCOVA model analysis on Eating/Diet Impact

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.8239

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.202

Confidence interval

level

95%

sides

2-sided

lower limit

-1.57

upper limit

1.98

Notes
[17] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis on Social Impact

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

P-value

= 0.7623

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.147

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.1

Notes
[18] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis on Emotional Impact

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

= 0.9898

Method

ANCOVA

Parameter type

Difference of Least Squares Means

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

1.49

Notes
[19] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis on Disease Anxiety

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

= 0.4603

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

0.386

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

1.41

Notes
[20] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis on Swallowing Anxiety

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.6613

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.162

Confidence interval

level

95%

sides

2-sided

lower limit

-0.89

upper limit

0.56

Notes
[21] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

ANCOVA model analysis on Total Score

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

= 0.6965

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

1.017

Confidence interval

level

95%

sides

2-sided

lower limit

-4.09

upper limit

6.13

Notes
[22] - For any patients with intercurrent events, the EoE-QoL-A scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Secondary: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 24

Top of page

End point title

Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 24

End point description

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).

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	83	81
Units: Score
least squares mean (confidence interval 95%)
Physical functioning	0.2 (-1.36 to 1.70)	0.5 (-0.98 to 1.97)
Role limitations due to physical health	0.5 (-1.03 to 2.10)	1.5 (-0.06 to 2.99)
Bodily pain	-0.6 (-2.92 to 1.82)	0.2 (-2.07 to 2.53)
General health perceptions	-0.9 (-2.62 to 0.78)	-0.9 (-2.54 to 0.76)
Vitality	-0.5 (-2.47 to 1.54)	-0.5 (-2.50 to 1.48)
Social functioning	-1.5 (-3.84 to 0.92)	0.1 (-2.26 to 2.39)
Role limitations due to emotional problems	-1.1 (-3.68 to 1.51)	-0.4 (-2.95 to 2.15)
Mental health	-1.7 (-3.83 to 0.51)	-0.8 (-2.91 to 1.31)
Psychometrically-based physical summary score	0.4 (-1.21 to 2.01)	0.8 (-0.75 to 2.34)
Mental health component summary scores	-1.8 (-4.10 to 0.53)	-1.2 (-3.44 to 1.11)

Physical functioning

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.6852

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.93

upper limit

1.27

Notes
[23] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Role limitations due to physical health

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[24]

P-value

= 0.2685

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.57

upper limit

0.72

Notes
[24] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Bodily pain

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.538

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.27

upper limit

1.71

Notes
[25] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

General health perceptions

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

P-value

= 0.9734

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.81

upper limit

1.75

Notes
[26] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Vitality

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

= 0.9653

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.09

upper limit

2.19

Notes
[27] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Role limitations due to emotional problems

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[28]

P-value

= 0.6274

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

2.08

Notes
[28] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Social functioning

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.2326

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.04

upper limit

0.98

Notes
[29] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Psychometrically-based physical summary score

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

= 0.6456

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

1.28

Notes
[30] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Mental health

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.4599

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.14

upper limit

1.42

Notes
[31] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Mental health component summary scores

Statistical analysis description

Model: Change from baseline item score = Treatment + baseline item score + Region + Baseline steroid use + Presence of strictures at baseline.

Comparison groups

Benralizumab v Placebo

Number of subjects included in analysis

164

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.6206

Method

ANCOVA

Parameter type

Difference in Least Squares Means

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.08

upper limit

1.84

Notes
[32] - For any patients with intercurrent events, the SF-36 domain scores after the occurrence of those events were imputed using return-to-baseline MI. Missing data not due to intercurrent events were imputed using MI (MAR).

Secondary: Percent of patients with relevant concomitant procedures and healthcare resource utilization at Week 24 and Week 52.

Top of page

End point title

Percent of patients with relevant concomitant procedures and healthcare resource utilization at Week 24 and Week 52.

End point description

Percent of patients with any relevant concomitant procedures and healthcare resource utilization at Week 24 and Week 52.

End point type

Secondary

End point timeframe

Week 24, Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Participants
Week 24	3	5
Week 52	0	2

No statistical analyses for this end point

Secondary: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 24

Top of page

End point title

Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	96	95
Units: Participants
No symptoms	4	11
Very mild	23	27
Mild	34	32
Moderate	29	17
Severe	3	6
Very Severe	3	2

No statistical analyses for this end point

Secondary: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 24

Top of page

End point title

Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	96	96
Units: Participants
Much better	13	13
Moderately better	13	17
A little better	21	20
About the same	37	36
A little worse	7	6
Moderately worse	3	3
Much worse	2	1

No statistical analyses for this end point

Secondary: Benralizumab Pharmacokinetics for Double Blind Period

Top of page

End point title

Benralizumab Pharmacokinetics for Double Blind Period

End point description

Serum concentrations of benralizumab through Week 24. Geometric mean calculated using log transformed data.

End point type

Secondary

End point timeframe

Up to week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	97	0 ^[33]
Units: ng/mL
geometric mean (confidence interval 95%)
Week 8 (n = 95)	1555.70 (1425.31 to 1698.02)	( to )
Week 16 (n = 91)	1582.46 (1322.66 to 1893.30)	( to )
Week 24 (n = 85)	1338.65 (1027.05 to 1744.78)	( to )

Notes
[33] - Placebo treatment, so no PK data till after week 24 (where values were mean = BLQ, CI = NA to NA)

No statistical analyses for this end point

Secondary: Benralizumab Pharmacokinetics for Open Label Period

Top of page

End point title

Benralizumab Pharmacokinetics for Open Label Period

End point description

Serum concentrations of benralizumab in Weeks 36 and 52. Geometric mean calculated using log transformed data.

End point type

Secondary

End point timeframe

Week 36, Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	97	96
Units: ng/mL
geometric mean (confidence interval 95%)
Week 36 (n = 67, 63)	1405.94 (985.94 to 2004.86)	1362.27 (1051.69 to 1764.58)
Week 52 (n = 30, 36)	1278.13 (749.19 to 2180.52)	1495.61 (975.73 to 2292.50)

No statistical analyses for this end point

Secondary: Immunogenicity of benralizumab in Double Blind period

Top of page

End point title

Immunogenicity of benralizumab in Double Blind period

End point description

Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind period. Note: TE = Treatment Emergent. *Condition = maximum titre >median of maximum titres. Last two categories for placebo group recorded as 0, but no data calculated (due to placebo treatment).

End point type

Secondary

End point timeframe

Up to Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Participants
ADA positive/ADA prevalence (n = 103, 107)	18	8
ADA negative (n = 103, 107)	85	99
TE ADA positive/ADA incidence (n = 102, 106)	18	4
ADA persistently positive (n = 102, 106)	18	3
ADA positive with condition* (n = 103, 107)	6	4
nAb positive/nAb prevalence (n = 103)	10	0
ADA persistently positive + nAb positive (n = 102)	10	0

No statistical analyses for this end point

Secondary: Immunogenicity of benralizumab in Double Blind + Open Label periods

Top of page

End point title

Immunogenicity of benralizumab in Double Blind + Open Label periods

End point description

Immunogenicity of benralizumab assessed by ADA and nAb in the Double Blind and Open Label periods. Note: TE = Treatment Emergent. *Condition = maximum titre >median of maximum titres. Pos = positive.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Participants
ADA positive/ADA prevalence (n = 103, 105)	19	17
ADA negative (n = 103, 105)	84	88
TE ADA positive/ADA incidence (n = 102, 105)	19	11
ADA persistently positive (n = 102, 105)	16	10
ADA positive with condition* (n = 103, 105)	7	7
nAb positive/nAb prevalence (n = 103, 105)	10	5
ADA persistently pos. & nAb pos. (n = 102, 105)	10	5

No statistical analyses for this end point

Other pre-specified: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 52

Top of page

End point title

Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 52

End point description

Proportion of patients with a histologic response at Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count <= 6 eos/hpf across all available esophageal levels. 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.

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	46	47
Units: Percentage of Participants
number (confidence interval 95%)	82.6 (71.66 to 93.56)	89.4 (80.55 to 98.18)

No statistical analyses for this end point

Other pre-specified: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 52

Top of page

End point title

Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	41	45
Units: Score
least squares mean (confidence interval 95%)	-19.409 (-25.65 to -13.17)	-19.806 (-25.70 to -13.91)

No statistical analyses for this end point

Other pre-specified: Change from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 52

Top of page

End point title

Change from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	41	41
Units: Score
least squares mean (confidence interval 95%)	-0.3 (-0.90 to 0.32)	-0.7 (-1.35 to -0.09)

No statistical analyses for this end point

Other pre-specified: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 52

Top of page

End point title

Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 52

End point description

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.

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	31	41
Units: Days
arithmetic mean (standard deviation)	19.33 ( 10.950 )	20.8 ( 10.472 )

No statistical analyses for this end point

Other pre-specified: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

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End point title

Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	31	41
Units: Days
arithmetic mean (standard deviation)	6.8 ( 11.59 )	6.2 ( 9.83 )

No statistical analyses for this end point

Other pre-specified: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 52

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End point title

Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	46	49
Units: Score
least squares mean (confidence interval 95%)
Dysphagia-related pain	-0.511 (-1.40 to 0.38)	-0.776 (-1.65 to 0.10)
Dysphagia-related discomfort	-0.456 (-1.14 to 0.22)	-0.625 (-1.30 to 0.05)
Overall episode severity	-0.522 (-1.26 to 0.22)	-0.732 (-1.48 to 0.02)

No statistical analyses for this end point

Other pre-specified: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 52

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End point title

Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	41	45
Units: Score
least squares mean (confidence interval 95%)
Abdominal pain severity	-0.826 (-1.44 to -0.22)	-1.039 (-1.62 to -0.46)
Nausea severity	-0.855 (-1.43 to -0.28)	-0.960 (-1.50 to -0.42)

No statistical analyses for this end point

Other pre-specified: Change from baseline in PEES at Week 52

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End point title

Change from baseline in PEES at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	6	6
Units: Score
arithmetic mean (standard deviation)	-6.5 ( 18.04 )	-12.5 ( 15.67 )

No statistical analyses for this end point

Other pre-specified: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52

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End point title

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

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	43	47
Units: Score
least squares mean (confidence interval 95%)
Eating/Diet Impact	1.408 (-1.01 to 3.83)	1.949 (-0.32 to 4.21)
Social Impact	1.462 (0.09 to 2.83)	1.984 (0.70 to 3.27)
Emotional Impact	1.768 (-0.21 to 3.75)	2.451 (0.58 to 4.33)
Disease Anxiety	1.063 (-0.43 to 2.56)	1.152 (-0.27 to 2.57)
Swallowing Anxiety	0.677 (-0.37 to 1.72)	1.085 (0.10 to 2.07)
Total Score	6.749 (-0.35 to 13.84)	8.714 (2.03 to 15.40)

No statistical analyses for this end point

Other pre-specified: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 52

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End point title

Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	34	38
Units: Score
least squares mean (confidence interval 95%)
Physical functioning	0.3 (-1.86 to 2.51)	0.4 (-1.60 to 2.46)
Role limitations due to physical health	-0.5 (-3.27 to 2.20)	0.9 (-1.63 to 3.51)
Bodily pain	0.6 (-2.69 to 3.97)	1.8 (-1.34 to 5.00)
General health perceptions	2.3 (-0.71 to 5.39)	0.7 (-2.17 to 3.59)
Vitality	-0.2 (-2.69 to 2.31)	-2.0 (-4.42 to 0.44)
Social functioning	0.2 (-3.73 to 4.17)	-0.5 (-4.26 to 3.34)
Role limitations due to emotional problems	-0.1 (-3.30 to 3.19)	-0.3 (-3.39 to 2.76)
Mental health	1.2 (-1.37 to 3.69)	-1.1 (-3.46 to 1.30)
Psychometrically-based physical summary score	0.5 (-2.15 to 3.18)	1.4 (-1.15 to 3.85)
Mental health component summary scores	0.5 (-2.44 to 3.50)	-1.9 (-4.78 to 0.89)

No statistical analyses for this end point

Other pre-specified: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 52

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End point title

Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	36	42
Units: Participants
No symptoms	6	10
Very mild	12	14
Mild	9	13
Moderate	8	5
Severe	0	0
Very Severe	1	0

No statistical analyses for this end point

Other pre-specified: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 52

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End point title

Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 52

End point description

End point type

Other pre-specified

End point timeframe

Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	36	43
Units: Participants
Much better	12	13
Moderately better	3	12
A little better	8	12
About the same	9	6
A little worse	4	0
Moderately worse	0	0
Much worse	0	0

No statistical analyses for this end point

Other pre-specified: Safety and tolerability in Double Blind Period

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End point title

Safety and tolerability in Double Blind Period

End point description

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

End point type

Other pre-specified

End point timeframe

Up to Week 24

End point values	Benralizumab	Placebo
Number of subjects analysed	103	107
Units: Participants
Any AE	66	66
Any SAE	2	1

No statistical analyses for this end point

Other pre-specified: Safety and tolerability in the Open Label period

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End point title

Safety and tolerability in the Open Label period

End point description

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

End point type

Other pre-specified

End point timeframe

From Week 24 up to Week 52

End point values	Benralizumab	Placebo
Number of subjects analysed	100	105
Units: Participants
Any AE	53	60
Any SAE	2	4

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On study AEs were collected from the first dose to the last date in study.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Placebo

Reporting group description

Matching Placebo injection delivered subcutaneously every 4 weeks through week 24, then 30mg Benralizumab injection delivered subcutaneously every 4 weeks after week 24

Reporting group title

Benra 30 mg

Reporting group description

30mg Benralizumab injection delivered subcutaneously every 4 weeks

Serious adverse events	Placebo	Benra 30 mg
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 107 (5.61%)	4 / 103 (3.88%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Oesophageal food impaction
subjects affected / exposed	2 / 107 (1.87%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal perforation
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumoperitoneum
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumomediastinum
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Affective disorder
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Oppositional defiant disorder
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Disruptive mood dysregulation disorder
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia bacterial
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 107 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 107 (0.93%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 3%

Non-serious adverse events	Placebo	Benra 30 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	69 / 107 (64.49%)	61 / 103 (59.22%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 107 (0.93%)	4 / 103 (3.88%)
occurrences all number	1	4
Nervous system disorders
Headache
subjects affected / exposed	12 / 107 (11.21%)	12 / 103 (11.65%)
occurrences all number	19	15
General disorders and administration site conditions
Influenza like illness
subjects affected / exposed	6 / 107 (5.61%)	3 / 103 (2.91%)
occurrences all number	6	5
Injection site erythema
subjects affected / exposed	3 / 107 (2.80%)	5 / 103 (4.85%)
occurrences all number	4	13
Pyrexia
subjects affected / exposed	5 / 107 (4.67%)	3 / 103 (2.91%)
occurrences all number	6	3
Immune system disorders
Immunisation reaction
subjects affected / exposed	1 / 107 (0.93%)	4 / 103 (3.88%)
occurrences all number	1	4
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	6 / 107 (5.61%)	2 / 103 (1.94%)
occurrences all number	6	2
Diarrhoea
subjects affected / exposed	7 / 107 (6.54%)	7 / 103 (6.80%)
occurrences all number	11	7
Dyspepsia
subjects affected / exposed	4 / 107 (3.74%)	0 / 103 (0.00%)
occurrences all number	4	0
Nausea
subjects affected / exposed	4 / 107 (3.74%)	4 / 103 (3.88%)
occurrences all number	4	4
Vomiting
subjects affected / exposed	4 / 107 (3.74%)	1 / 103 (0.97%)
occurrences all number	4	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	2 / 107 (1.87%)	6 / 103 (5.83%)
occurrences all number	2	6
Asthma
subjects affected / exposed	7 / 107 (6.54%)	5 / 103 (4.85%)
occurrences all number	9	5
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 107 (4.67%)	1 / 103 (0.97%)
occurrences all number	5	1
Back pain
subjects affected / exposed	1 / 107 (0.93%)	4 / 103 (3.88%)
occurrences all number	2	4
Infections and infestations
Nasopharyngitis
subjects affected / exposed	11 / 107 (10.28%)	12 / 103 (11.65%)
occurrences all number	15	20
Influenza
subjects affected / exposed	4 / 107 (3.74%)	0 / 103 (0.00%)
occurrences all number	4	0
Pharyngitis
subjects affected / exposed	0 / 107 (0.00%)	5 / 103 (4.85%)
occurrences all number	0	5
Upper respiratory tract infection
subjects affected / exposed	7 / 107 (6.54%)	4 / 103 (3.88%)
occurrences all number	11	4
COVID-19
subjects affected / exposed	27 / 107 (25.23%)	34 / 103 (33.01%)
occurrences all number	28	38
Gastroenteritis
subjects affected / exposed	4 / 107 (3.74%)	1 / 103 (0.97%)
occurrences all number	6	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

31 Jul 2020

The primary rationale for this amendment is to add study mitigation language which will provide sites with measures that may be implemented if a patient is not able to visit a study site to ensure that the clinical trial can continue whilst minimizing risk to the patient, maintaining compliance with GCP, and minimizing risks to the study integrity. The Qualitative Patient Interview Sub-study (Section 8.11.1) was also added. In addition, inclusion/exclusion criteria were clarified, and Table 9 of Restrictions (Section 6.5.4) was updated with clarifications regarding medications allowed, restricted and prohibited prior to screening. Finally, some minor clarifications were made to ensure correct interpretation of the protocol.

26 Aug 2020

11 Feb 2021

The primary rationale for this amendment is to update the duration of the OLE-period to at least 1 year (variable duration) and to include the option of at-home or remote location self-IP administration after week 52. Inclusion/exclusion criteria were clarified, the primary estimand approach for the analyses of study data was updated to a composite strategy to more accurately account for the occurrence of the described intercurrent events which are considered to reflect a treatment failure outcome. In addition, some minor clarifications were made to ensure correct interpretation of the protocol.

30 Apr 2021

The primary rationale for this amendment is to add the early time point sub-study. The substudy aims to generate early time point evidence of eosinophil depletion in tissue and to understand its relationship with endoscopic findings and symptom response. In addition, some minor clarifications were made to ensure correct interpretation of the protocol.

01 Apr 2022

The rationale for this amendment is to adjust the ordering of endpoints within the multiple testing procedure and update the analysis method for treatment failure intercurrent events for continuous endpoints. In addition, some minor clarifications were made to ensure correct interpretation of the protocol.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis (MESSINA)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 24.

Primary: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 24.

Primary: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 24

Primary: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 24

Secondary: Percent change from baseline in tissue eosinophils at Week 24

Secondary: Percent change from baseline in tissue eosinophils at Week 24

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total grade score at Week 24

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total grade score at Week 24

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total stage score at Week 24

Secondary: Change from baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) total stage score at Week 24

Secondary: Changes from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 24

Secondary: Changes from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 24

Secondary: Treatment responder rate, 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

Secondary: Treatment responder rate, 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

Secondary: Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24

Secondary: Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24

Secondary: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 24

Secondary: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 24

Secondary: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

Secondary: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24

Secondary: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24

Secondary: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24

Secondary: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24

Secondary: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24

Secondary: Changes from baseline in PEESS at Week 24

Secondary: Changes from baseline in PEESS at Week 24

Secondary: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24

Secondary: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24

Secondary: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 24

Secondary: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 24

Secondary: Percent of patients with relevant concomitant procedures and healthcare resource utilization at Week 24 and Week 52.

Secondary: Percent of patients with relevant concomitant procedures and healthcare resource utilization at Week 24 and Week 52.

Secondary: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 24

Secondary: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 24

Secondary: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 24

Secondary: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 24

Secondary: Benralizumab Pharmacokinetics for Double Blind Period

Secondary: Benralizumab Pharmacokinetics for Double Blind Period

Secondary: Benralizumab Pharmacokinetics for Open Label Period

Secondary: Benralizumab Pharmacokinetics for Open Label Period

Secondary: Immunogenicity of benralizumab in Double Blind period

Secondary: Immunogenicity of benralizumab in Double Blind period

Secondary: Immunogenicity of benralizumab in Double Blind + Open Label periods

Secondary: Immunogenicity of benralizumab in Double Blind + Open Label periods

Other pre-specified: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 52

Other pre-specified: Proportion of patients with a histologic response, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf at Week 52

Other pre-specified: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 52

Other pre-specified: Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) at Week 52

Other pre-specified: Change from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 52

Other pre-specified: Change from baseline in centrally-read Endoscopic Reference Score (EREFS) at Week 52

Other pre-specified: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 52

Other pre-specified: Dysphagia-free days as captured by the Dysphagia Symptom Questionnaire (DSQ) at Week 52

Other pre-specified: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

Other pre-specified: Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52

Other pre-specified: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 52

Other pre-specified: Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 52

Other pre-specified: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 52

Other pre-specified: Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 52

Other pre-specified: Change from baseline in PEES at Week 52

Other pre-specified: Change from baseline in PEES at Week 52

Other pre-specified: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52

Other pre-specified: Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52

Other pre-specified: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 52

Other pre-specified: Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) at Week 52

Other pre-specified: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 52

Other pre-specified: Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) at Week 52

Other pre-specified: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 52

Other pre-specified: Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) at Week 52

Other pre-specified: Safety and tolerability in Double Blind Period

Other pre-specified: Safety and tolerability in Double Blind Period

Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis (MESSINA)