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Clinical Trial Results:
A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)

Summary
EudraCT number	2018-000844-25
Trial protocol	DE FR SE GB NL PT BE IT ES
Global end of trial date	07 Jun 2022

Results information
Results version number	v1(current)
This version publication date	22 Dec 2022
First version publication date	22 Dec 2022
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

R668-EE-1774

ISRCTN number

US NCT number

NCT03633617

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron Pharmaceuticals, Inc.

Sponsor organisation address

777 Old Saw Mill River Rd., Tarrytown, NY, United States, 10591

Public contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com

Scientific contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001501-PIP04-19

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

07 Jun 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Jun 2022

Was the trial ended prematurely?

Main objective of the trial

The primary objectives of the study by study part are: Part A: To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B. (Participants enrolled in Part A may not participate in Part B) Part B: To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures. Part C: To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.

Protection of trial subjects

It is the responsibility of both the sponsor and the investigators to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the International Council for Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Sep 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

Canada: 9

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Netherlands: 4

Country: Number of subjects enrolled

Sweden: 1

Country: Number of subjects enrolled

United States: 272

Worldwide total number of subjects

321

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)

220

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Part A (24-week double-blind treatment period [DBTP]):157 participants screened, 81 randomized and received at least 1 dose of study drug; Part B (24-week DBTP): 462 participants screened, 240 randomized, 239 received treatment (1 participant randomized to placebo did not meet eligibility criteria and was discontinued prior to being treated).

Period 1 title

Double-blind, placebo-controlled

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Assessor, Monitor

Are arms mutually exclusive

Yes

Part A: Placebo

Arm description

Participants received placebo matching dupilumab subcutaneously (SC) during Part A (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part A entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching dupilumab

Part A: Dupilumab 300 mg QW

Arm description

Participants received dupilumab 300 milligrams (mg) SC once per week (QW) during Part A (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part A entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Part B: Placebo

Arm description

Participants received placebo matching dupilumab SC during Part B (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part B entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching dupilumab

Part B: Dupilumab 300 mg Q2W

Arm description

Participants received dupilumab 300 mg once every 2 weeks (Q2W) SC during Part B (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part B entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once every 2 weeks (Q2W); a SC injection of placebo was delivered in between dupilumab doses to maintain injection frequency between groups.

Part B: Dupilumab 300 mg QW

Arm description

Participants received dupilumab 300 mg SC once per week (QW) during Part B (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part B entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Number of subjects in period 1	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Started	39	42	79	81	80
Completed week 24 (Part A ; Part B)	37	40	74	79	75
Completed	37	40	74	79	75
Not completed	2	2	5	2	5
COVID-19 Restrictions	-	-	1	-	-
Consent withdrawn by subject	-	1	1	-	2
Physician decision	-	-	-	-	1
Adverse event, non-fatal	-	1	2	2	1
Unconfirmed early termination visit	1	-	-	-	-
Pregnancy	1	-	-	-	-
Lost to follow-up	-	-	-	-	1
Randomized, but no study drug (did not qualify)	-	-	1	-	-

Period 2 title

Extended active treatment & follow-up

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Only participants entering Part C from Part B were blinded to treatment regimen in Part C.

Are arms mutually exclusive

Yes

Part A/C: Placebo / Dupilumab 300 mg QW

Arm description

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW

Arm description

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Part B/C: Placebo / Dupilumab 300 mg Q2W

Arm description

Participants randomized to placebo in Part B were re-randomized in a 1:1 ratio to receive dupilumab 300 mg Q2W for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once every 2 weeks (Q2W); a SC injection of placebo was delivered in between dupilumab doses to maintain injection frequency between groups.

Part B/C: Placebo / Dupilumab 300 mg QW

Arm description

Participants randomized to placebo in Part B were re-randomized in a 1:1 ratio to receive dupilumab 300 mg QW for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W

Arm description

Participants randomized to dupilumab 300 mg Q2W in Part B continued to receive the same regimen for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once every 2 weeks (Q2W); a SC injection of placebo was delivered in between dupilumab doses to maintain injection frequency between groups.

Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW

Arm description

Participants randomized to dupilumab 300 mg QW during Part B, continued to receive the same regimen for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Arm type

Experimental

Investigational medicinal product name

dupilumab

Investigational medicinal product code

REGN668

Other name

DUPIXENT

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Dupilumab 300 mg delivered subcutaneously (SC) once weekly (QW)

Number of subjects in period 2 ^[1]	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Started	37	40	37	37	79	74
Completed week 52 treatment (Part C)	32	38	34	36	74	65
Completed	30	35	33	36	67	64
Not completed	7	5	4	1	12	10
Consent withdrawn by subject	2	2	-	1	1	6
Physician decision	-	-	1	-	-	1
Adverse event, non-fatal	1	-	1	-	-	-
Pregnancy	-	-	-	-	1	-
COVID-19 related	1	-	-	-	-	-
Lost to follow-up	3	3	1	-	7	2
Lack of efficacy	-	-	1	-	-	-
Protocol deviation	-	-	-	-	3	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's week 24 visit in Part A was delayed due to COVID-19; afterwards, participant moved to Part C

Baseline characteristics

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Reporting group title

Part A: Placebo

Reporting group description

Reporting group title

Part A: Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part B: Placebo

Reporting group description

Reporting group title

Part B: Dupilumab 300 mg Q2W

Reporting group description

Reporting group title

Part B: Dupilumab 300 mg QW

Reporting group description

Reporting group values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW	Total
Number of subjects	39	42	79	81	80	321
Age Categorical
Age
Units: Participants
≥ 12 to < 18 years old	9	11	26	27	26	99
≥ 18 to < 40 years old	22	13	38	35	38	146
≥ 40 to < 65 years old	8	18	15	18	15	74
≥ 65 years old	0	0	0	1	1	2
Sex: Female, Male
Units: Participants
Female	18	14	21	36	30	119
Male	21	28	58	45	50	202
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	4	5	3	5	18
Not Hispanic or Latino	38	38	74	77	75	302
Unknown or Not Reported	0	0	0	1	0	1
Race/Ethnicity, Customized
Race
Units: Subjects
White	37	41	72	74	71	295
Black or African American	1	1	3	3	2	10
Asian	0	0	1	1	3	5
Other	1	0	2	2	3	8
Not reported	0	0	1	1	1	3
Dysphagia Symptom Questionnaire (DSQ) Total Score
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Units: Score on a Scale
arithmetic mean (standard deviation)	35.1 ± 12.11	32.2 ± 12.66	36.1 ± 10.55	35.6 ± 12.24	38.4 ± 10.70	-
Peak Eosinophils (eos) Count of Three Regions per High-power Field (/hpf)
Units: Eosinophils/high-power field (eos/hpf)
arithmetic mean (standard deviation)	96.5 ± 54.69	82.6 ± 41.02	84.3 ± 41.20	87.7 ± 49.37	89.2 ± 46.67	-
Eosinophilic Esophagitis (EoE) Histological Grade Calculated Mean Score (0 - 3)
Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities.
Units: Score on a Scale
arithmetic mean (standard deviation)	1.324 ± 0.4676	1.260 ± 0.4088	1.226 ± 0.3996	1.245 ± 0.3721	1.305 ± 0.3882	-
Eosinophilic Esophagitis (EoE) Histological Stage Calculated Mean Score (0 - 3)
Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities.
Units: Score on a Scale
arithmetic mean (standard deviation)	1.376 ± 0.3972	1.299 ± 0.3334	1.216 ± 0.3608	1.248 ± 0.3182	1.294 ± 0.3256	-

End points

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Reporting group title

Part A: Placebo

Reporting group description

Reporting group title

Part A: Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part B: Placebo

Reporting group description

Reporting group title

Part B: Dupilumab 300 mg Q2W

Reporting group description

Reporting group title

Part B: Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part A/C: Placebo / Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part B/C: Placebo / Dupilumab 300 mg Q2W

Reporting group description

Reporting group title

Part B/C: Placebo / Dupilumab 300 mg QW

Reporting group description

Reporting group title

Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W

Reporting group description

Reporting group title

Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW

Reporting group description

Primary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 24

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End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 24

End point description

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). Part A Full Analysis Set (FAS): All participants randomized to Part A (Participants considered non-responder after rescue treatment use and multiple imputation (MI) method for missing due to COVID-19; Participants considered non-responder for missing not due to COVID-19); Part B FAS: All participants randomized to Part B (Participants considered non-responder after rescue treatment use or missing not due to COVID-19 and MI method for missing or dosing interruption due to COVID-19)

End point type

Primary

End point timeframe

At week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Participants
number (confidence interval 95%)	5.1 (0.63 to 17.32)	59.5 (43.28 to 74.37)	6.3 (2.09 to 14.16)	60.5 (49.01 to 71.19)	58.8 (47.18 to 69.65)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is dupilumab minus placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

55.3

Confidence interval

level

95%

sides

2-sided

lower limit

39.58

upper limit

71.04

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Difference is dupilumab minus placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

43.44

upper limit

68.54

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is dupilumab minus placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

53.5

Confidence interval

level

95%

sides

2-sided

lower limit

41.2

upper limit

65.79

Primary: Absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) total score at week 24

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End point title

Absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) total score at week 24

End point description

The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. Part A Full Analysis Set (FAS): All participant randomized to Part A (MI method for missing data or data set to missing after rescue treatment use); Part B FAS: All participants randomized to Part B (MI method for missing data or data set to missing after rescue treatment use)

End point type

Primary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-9.60 (-15.056 to -4.136)	-21.92 (-26.870 to -16.967)	-13.86 (-17.605 to -10.120)	-14.37 (-18.018 to -10.723)	-23.78 (-27.427 to -20.131)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-12.32

Confidence interval

level

95%

sides

2-sided

lower limit

-19.107

upper limit

-5.537

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-9.92

Confidence interval

level

95%

sides

2-sided

lower limit

-14.811

upper limit

-5.022

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8393

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-5.423

upper limit

4.406

Secondary: Percent change from baseline in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 24

Top of page

End point title

Percent change from baseline in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 24

End point description

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease. Part A FAS (Worst-observation carried forward [WOCF]-MI method with WOCF for rescue treatment use and missing not due to COVID-19; MI method for missing due to COVID-19); Part B FAS (WOCF-MI method with WOCF for rescue treatment use and missing not due to COVID-19 and MI method for missing or dosing interruption due to COVID-19)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Change
least squares mean (confidence interval 95%)	-2.98 (-17.886 to 11.921)	-71.24 (-84.863 to -57.613)	8.38 (-11.677 to 28.433)	-70.84 (-87.095 to -54.585)	-80.24 (-96.589 to -63.895)

Part A: Placebo; Part A: Dupilumab 300 mg QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-68.26

Confidence interval

level

95%

sides

2-sided

lower limit

-86.896

upper limit

-49.615

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-88.62

Confidence interval

level

95%

sides

2-sided

lower limit

-112.194

upper limit

-65.046

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab 300 mg Q2W vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-79.22

Confidence interval

level

95%

sides

2-sided

lower limit

-103.098

upper limit

-55.338

Secondary: Percent change from baseline in DSQ total score at week 24

Top of page

End point title

Percent change from baseline in DSQ total score at week 24

End point description

The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. Part A FAS (MI method for missing data or data set to missing after rescue treatment use); Part B FAS (MI method for missing data or data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Change
least squares mean (confidence interval 95%)	-31.68 (-47.545 to -15.818)	-69.17 (-83.578 to -54.752)	-41.43 (-51.749 to -31.116)	-45.78 (-55.658 to -35.904)	-64.32 (-74.267 to 54.382)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-37.48

Confidence interval

level

95%

sides

2-sided

lower limit

-57.222

upper limit

-17.745

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab 300 mg Q2W vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5243

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4.35

Confidence interval

level

95%

sides

2-sided

lower limit

-17.734

upper limit

9.038

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-22.89

Confidence interval

level

95%

sides

2-sided

lower limit

-36.272

upper limit

-9.513

Secondary: Absolute change from baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) mean Grade score at week 24

Top of page

End point title

Absolute change from baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) mean Grade score at week 24

End point description

Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities. Part A FAS (WOCF-MI method with WOCF for rescue treatment use and missing not due to COVID-19; MI method for missing due to COVID-19); Part B FAS (WOCF-MI method with WOCF for rescue treatment use and missing not due to COVID-19 and MI method for missing or dosing interruption due to COVID-19)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-0.001 (-0.1166 to 0.1139)	-0.761 (-0.8732 to -0.6484)	-0.148 (-0.2379 to -0.0584)	-0.814 (-0.8958 to -0.7317)	-0.830 (-0.9136 to -0.7463)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.759

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9061

upper limit

-0.6127

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.682

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7929

upper limit

-0.5707

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab 300 mg Q2W vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.666

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7773

upper limit

-0.5538

Secondary: Absolute change from baseline in EoEHSS mean Stage score at week 24

Top of page

End point title

Absolute change from baseline in EoEHSS mean Stage score at week 24

End point description

Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities. Part A FAS (WOCF-MI method with WOCF for rescue treatment use and missing not due to COVID-19; MI method for missing due to COVID-19); Part B FAS (WOCF-MI Method with WOCF for Rescue Treatment Use and Missing Not Due to COVID-19 and MI Method for Missing or Dosing Interruption Due to COVID-19)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-0.012 (-0.1243 to 0.0995)	-0.753 (-0.8627 to -0.6441)	-0.132 (-0.2179 to -0.0464)	-0.793 (-0.8713 to -0.7144)	-0.804 (-0.8839 to -0.7237)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.741

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8842

upper limit

-0.5978

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.672

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7778

upper limit

-0.5655

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab 300 mg Q2W vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.661

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7674

upper limit

-0.554

Secondary: Absolute change from baseline in EoE Endoscopic Reference total Score (EoE-EREFS) at week 24

Top of page

End point title

Absolute change from baseline in EoE Endoscopic Reference total Score (EoE-EREFS) at week 24

End point description

EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease. Part A FAS (WOCF-MI method with WOCF for rescue treatment use and missing not due to COVID-19; MI method for missing due to COVID-19); Part B FAS (WOCF-MI Method with WOCF for Rescue Treatment Use and Missing Not Due to COVID-19 and MI Method for Missing or Dosing Interruption Due to COVID-19)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-0.3 (-1.11 to 0.50)	-3.2 (-3.98 to -2.38)	-0.6 (-1.37 to 0.12)	-4.6 (-5.24 to -3.89)	-4.5 (-5.17 to -3.77)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.91

upper limit

-1.84

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab 300 mg QW vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.77

upper limit

-2.93

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab 300 mg Q2W vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.86

upper limit

-3.02

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 24

Top of page

End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 24

End point description

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). Part A FAS (Participants considered non-responder after rescue treatment use and MI method for missing due to COVID-19; Participants considered non-responder for missing not due to COVID-19); Part B FAS (Participants considered non-responder after rescue treatment use or missing not due to COVID-19 and MI method for missing or dosing interruption due to COVID-19).

End point type

Secondary

End point timeframe

At week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Participants
number (confidence interval 95%)	7.7 (1.62 to 20.87)	64.3 (48.03 to 78.45)	7.6 (2.84 to 15.80)	79.0 (68.54 to 87.27)	82.5 (72.38 to 90.09)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

57.5

Confidence interval

level

95%

sides

2-sided

lower limit

41.69

upper limit

73.33

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

74.9

Confidence interval

level

95%

sides

2-sided

lower limit

64.25

upper limit

85.5

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

72.4

Confidence interval

level

95%

sides

2-sided

lower limit

61.05

upper limit

83.7

Secondary: Normalized Enrichment Score (NES) for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 24

Top of page

End point title

Normalized Enrichment Score (NES) for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 24

End point description

NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. A NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease). Part A FAS (Participants with NES Score in Part A; Last observation carried forward [LOCF] method with data set to missing after rescue treatment use); Part B FAS (Participants with NES Score in Part B; LOCF method with data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	29	31	41	44	40
Units: Score on a Scale
median (not applicable)	-0.160 ± 99999	-2.660 ± 99999	-0.730 ± 99999	-2.675 ± 99999	-2.665 ± 99999

Part B:Placebo, Part B:Dupilumab 300 mg SC Q2W

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-1.84

Confidence interval

level

95%

sides

2-sided

lower limit

-2.42

upper limit

-1.11

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-2.25

Confidence interval

level

95%

sides

2-sided

lower limit

-2.72

upper limit

-1.73

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-1.85

Confidence interval

level

95%

sides

2-sided

lower limit

-2.44

upper limit

-1.15

Secondary: NES for the relative change from baseline in type 2 inflammation signature at week 24

Top of page

End point title

NES for the relative change from baseline in type 2 inflammation signature at week 24

End point description

NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. A NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease). Part A FAS (Participants with NES Score in Part A; LOCF Method with data set to missing after rescue treatment use); Part B FAS (Participants with NES Score in Part B; LOCF method with data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	29	31	41	44	40
Units: Score on a Scale
median (not applicable)	-0.320 ± 99999	-1.970 ± 99999	-0.640 ± 99999	-1.950 ± 99999	-1.930 ± 99999

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-1.59

Confidence interval

level

95%

sides

2-sided

lower limit

-1.74

upper limit

-1.27

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-1.275

Confidence interval

level

95%

sides

2-sided

lower limit

-1.82

upper limit

-1.07

Part B:Placebo, Part B:Dupilumab 300 mg SC Q2W

Statistical analysis description

Median Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Wilcoxon rank-sum test

Parameter type

Hodges-Lehmann estimator

Point estimate

-1.255

Confidence interval

level

95%

sides

2-sided

lower limit

-1.73

upper limit

-1.05

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 24

Top of page

End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 24

End point description

End point type

Secondary

End point timeframe

At week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Participants
number (confidence interval 95%)	0.0 (0.00 to 9.03)	21.4 (10.30 to 36.81)	1.3 (0.03 to 6.85)	27.2 (17.87 to 38.19)	28.8 (19.18 to 39.95)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

21.9

Confidence interval

level

95%

sides

2-sided

lower limit

9.42

upper limit

34.38

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

28.9

Confidence interval

level

95%

sides

2-sided

lower limit

18.36

upper limit

39.46

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

27.6

Confidence interval

level

95%

sides

2-sided

lower limit

17.2

upper limit

38.09

Secondary: Absolute change from baseline in health-related quality of life (QOL) average score as measured by EoE Impact Questionnaire (EoE-IQ) at week 24

Top of page

End point title

Absolute change from baseline in health-related quality of life (QOL) average score as measured by EoE Impact Questionnaire (EoE-IQ) at week 24

End point description

The EoE-IQ measures impact of EoE on emotional, social, work & school, & sleep aspects. Participants were asked to respond to 11 questions based on experience living with EoE during past 7 days. Response to each item is on a 5-point scale (1=Not at all [impacted] 2=A little, 3=Somewhat, 4=Quite a bit, 5=Extremely [impacted]). The average score is the sum of non-missing responses divided by the number of items with non-missing responses. The average score can range from 1 to 5; a higher score is indicative of a more negative impact. Part A FAS (MI method with data set to missing after rescue treatment use); Part B FAS (MI method with data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-0.246 (-0.4659 to -0.0266)	-0.614 (-0.8140 to -0.4149)	-0.578 (-0.6977 to -0.4585)	-0.593 (-0.7152 to -0.4706)	-0.887 (-1.0050 to -0.7685)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0077

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.368

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6388

upper limit

-0.0975

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.309

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4703

upper limit

-0.1471

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab group vs Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8586

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.015

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1782

upper limit

0.1485

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE Symptom Questionnaire (EoE-SQ) at week 24

Top of page

End point title

Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE Symptom Questionnaire (EoE-SQ) at week 24

End point description

The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the severity of each symptom based on the worst experience in the past 7 days is on a scale of 0 to 10 (higher is worse). The EoE-SQ severity score is calculated as the sum of the severity scores from questions 1 to 3 (chest pain, stomach pain, burning feeling in chest), which could range from 0 to 30; a higher score is indicative of more severe symptoms. Part A FAS (MI method with data set to missing after rescue treatment use); Part B FAS (MI method with data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-3.9 (-5.46 to -2.31)	-5.8 (-7.24 to -4.44)	-4.0 (-5.16 to -2.80)	-4.5 (-5.59 to -3.32)	-5.4 (-6.60 to -4.27)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0467

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.87

upper limit

-0.03

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5469

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.03

upper limit

1.08

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0718

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

0.13

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 24

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End point title

Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 24

End point description

The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the frequency of each symptom is on a 5-point scale (1 = ‘Never’, 2 = ‘One day’, 3 = ‘ 2-6 days’, 4 = ‘Once a day’, 5 = ‘More than once a day’). The EoE-SQ frequency score is calculated as the sum of the frequency scores from the 5 items which could range from 5 to 25; a higher score is indicative of higher frequency of symptoms. Part A FAS (MI method with data set to missing after rescue treatment use); Part B FAS (MI method with data set to missing after rescue treatment use)

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Score on a Scale
least squares mean (confidence interval 95%)	-1.7 (-2.67 to -0.71)	-3.4 (-4.29 to -2.53)	-2.6 (-3.25 to -1.87)	-3.0 (-3.69 to -2.36)	-3.9 (-4.61 to -3.25)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0051

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.93

upper limit

-0.52

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0037

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.45

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Dupilumab group vs. Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3152

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.38

upper limit

0.44

Secondary: Percentage of participants who received rescue medication during the 24-week double-blind, placebo-controlled treatment period

Top of page

End point title

Percentage of participants who received rescue medication during the 24-week double-blind, placebo-controlled treatment period

End point description

End point type

Secondary

End point timeframe

At week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	79	81	80
Units: Percentage of Participants
number (confidence interval 95%)	12.8 (4.30 to 27.43)	0.0 (0.00 to 8.41)	2.5 (0.31 to 8.85)	1.2 (0.03 to 6.69)	2.5 (0.30 to 8.74)

Part A: Placebo, Part A: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part A: Placebo v Part A: Dupilumab 300 mg QW

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

-12.7

Confidence interval

level

95%

sides

2-sided

lower limit

-23.21

upper limit

-2.26

Part B: Placebo, Part B: Dupilumab 300 mg SC Q2W

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg Q2W

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5493

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.51

upper limit

2.93

Part B: Placebo, Part B: Dupilumab 300 mg SC QW

Statistical analysis description

Difference is Dupilumab minus Placebo

Comparison groups

Part B: Placebo v Part B: Dupilumab 300 mg QW

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9887

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in proportion

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

5.02

Secondary: Concentration of functional dupilumab in serum at week 24

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End point title

Concentration of functional dupilumab in serum at week 24

End point description

The PK analysis set (PKAS) for Part A included all randomized participants who received any study drug and who had at least one non-missing drug concentration result following the first dose of study drug in the corresponding study part. The PKAS for Part B included all randomized participants who received any study drug and who had at least one non-missing drug concentration result following the first dose of study drug in the corresponding study part.

End point type

Secondary

End point timeframe

Up to week 24

End point values	Part A: Placebo	Part A: Dupilumab 300 mg QW	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg QW
Number of subjects analysed	39	42	76	79	76
Units: milligrams per liter (mg/L)
arithmetic mean (standard deviation)
Week 0 (n=38,41,75,77,73)	0 ± 0	0 ± 0	0.00553 ± 0.0479	0 ± 0	0 ± 0
Week 12 (n=37,42,72,67,65)	0 ± 0	187 ± 63.3	0.00118 ± 0.0100	70.2 ± 37.7	162 ± 83.7
Week 24 (n=33,36,67,68,63)	0 ± 0	197 ± 71.8	0 ± 0	72.1 ± 46.6	189 ± 98.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 52

Top of page

End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 52

End point description

Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

At week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Percentage of Participants
number (not applicable)	60.0	55.9	71.9	67.6	74.0	84.6

No statistical analyses for this end point

Secondary: Absolute change in DSQ total score at week 52

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End point title

Absolute change in DSQ total score at week 52

End point description

The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	23	29	27	24	52	54
Units: Score on a Scale
arithmetic mean (standard deviation)	-21.71 ± 17.143	-23.44 ± 16.149	-23.69 ± 13.737	-27.25 ± 11.457	-20.87 ± 16.387	-30.26 ± 15.389

No statistical analyses for this end point

Secondary: Percent change in DSQ total score at week 52

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End point title

Percent change in DSQ total score at week 52

End point description

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	23	29	27	24	52	54
Units: Percentage of Change
arithmetic mean (standard deviation)	-65.87 ± 49.705	-75.93 ± 36.892	-71.01 ± 37.256	-78.13 ± 31.003	-61.19 ± 44.447	-80.74 ± 32.866

No statistical analyses for this end point

Secondary: Absolute change in EoE-EREFS total score at week 52

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End point title

Absolute change in EoE-EREFS total score at week 52

End point description

EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	35	31	37	73	63
Units: Score on a Scale
arithmetic mean (standard deviation)	-3.9 ± 2.74	-4.1 ± 3.37	-4.3 ± 3.21	-6.1 ± 3.60	-5.2 ± 3.40	-5.3 ± 2.85

No statistical analyses for this end point

Secondary: Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 52

Top of page

End point title

Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 52

End point description

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Percentage of Change
arithmetic mean (standard deviation)	-83.76 ± 24.996	-88.59 ± 13.506	-91.20 ± 13.037	-84.21 ± 42.169	-84.78 ± 40.973	-95.85 ± 4.037

No statistical analyses for this end point

Secondary: Absolute change in EoEHSS mean Grade score at week 52

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End point title

Absolute change in EoEHSS mean Grade score at week 52

End point description

Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Score on a Scale
arithmetic mean (standard deviation)	-0.873 ± 0.5506	-0.873 ± 0.3537	-0.779 ± 0.4292	-0.906 ± 0.3936	-0.838 ± 0.4039	-0.968 ± 0.4293

No statistical analyses for this end point

Secondary: Absolute change in EoEHSS mean Stage score at week 52

Top of page

End point title

Absolute change in EoEHSS mean Stage score at week 52

End point description

Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Score on a Scale
arithmetic mean (standard deviation)	-0.874 ± 0.4630	-0.891 ± 0.2770	-0.710 ± 0.3783	-0.871 ± 0.3510	-0.809 ± 0.3434	-0.932 ± 0.3730

No statistical analyses for this end point

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 52

Top of page

End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 52

End point description

End point type

Secondary

End point timeframe

At week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Percentage of Participants
number (not applicable)	70.0	82.4	87.5	78.4	83.6	100

No statistical analyses for this end point

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 52

Top of page

End point title

Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 52

End point description

End point type

Secondary

End point timeframe

At week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	30	34	32	37	73	65
Units: Percentage of Participants
number (not applicable)	26.7	29.4	40.6	16.2	31.5	30.8

No statistical analyses for this end point

Secondary: Absolute change in health-related QOL average score as measured by EoE-IQ at week 52

Top of page

End point title

Absolute change in health-related QOL average score as measured by EoE-IQ at week 52

End point description

The EoE-IQ measures impact of EoE on emotional, social, work & school, & sleep aspects. Participants were asked to respond to 11 questions based on experience living with EoE during past 7 days. Response to each item is on a 5-point scale (1=Not at all [impacted] 2=A little, 3=Somewhat, 4=Quite a bit, 5=Extremely [impacted]). The average score is the sum of non-missing responses divided by the number of items with non-missing responses. The average score can range from 1 to 5; a higher score is indicative of a more negative impact. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	27	27	31	35	67	56
Units: Score on a Scale
arithmetic mean (standard deviation)	-0.954 ± 0.6690	-0.911 ± 0.6344	-1.021 ± 0.7169	-0.858 ± 0.6360	-0.773 ± 0.6217	-0.935 ± 0.6883

No statistical analyses for this end point

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Top of page

End point title

Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

End point description

The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the severity of each symptom based on the worst experience in the past 7 days is on a scale of 0 to 10 (higher is worse). The EoE-SQ severity score is calculated as the sum of the severity scores from questions 1 to 3 (chest pain, stomach pain, burning feeling in chest), which could range from 0 to 30; a higher score is indicative of more severe symptoms. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	27	27	32	35	68	57
Units: Score on a Scale
arithmetic mean (standard deviation)	-7.2 ± 6.46	-5.9 ± 6.80	-6.2 ± 6.42	-5.9 ± 6.47	-4.7 ± 5.99	-6.4 ± 6.86

No statistical analyses for this end point

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Top of page

End point title

Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

End point description

The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the frequency of each symptom is on a 5-point scale (1 = ‘Never’, 2 = ‘One day’, 3 = ‘ 2-6 days’, 4 = ‘Once a day’, 5 = ‘More than once a day’). The EoE-SQ frequency score is calculated as the sum of the frequency scores from the 5 items which could range from 5 to 25; a higher score is indicative of higher frequency of symptoms. Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	27	27	32	35	68	57
Units: Score on a Scale
arithmetic mean (standard deviation)	-4.3 ± 3.78	-3.2 ± 3.50	-4.0 ± 3.54	-3.8 ± 3.62	-3.6 ± 3.45	-4.7 ± 4.03

No statistical analyses for this end point

Secondary: Percentage of participants who received rescue medication during the 28-week extended active treatment period

Top of page

End point title

Percentage of participants who received rescue medication during the 28-week extended active treatment period

End point description

End point type

Secondary

End point timeframe

Baseline (of Part C) to week 28

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	37	40	37	37	79	74
Units: Percentage of Participants
number (not applicable)	8.1	0	2.7	2.7	0	1.4

No statistical analyses for this end point

Secondary: NES for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 52

Top of page

End point title

NES for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 52

End point description

NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease). Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	27	30	17	24	60	49
Units: Score on a Scale
median (full range (min-max))	-2.580 (-2.87 to -0.45)	-2.670 (-2.83 to -1.09)	-2.28 (-2.8 to -0.8)	-2.62 (-2.9 to -2.1)	-2.64 (-2.9 to 1.2)	-2.69 (-2.9 to -0.6)

No statistical analyses for this end point

Secondary: NES for the relative change in type 2 inflammation signature at week 52

Top of page

End point title

NES for the relative change in type 2 inflammation signature at week 52

End point description

NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease). Part C safety analysis set (SAF): All participants who were randomized in Part A/B, entered Part C, and received any study drug in Part C.

End point type

Secondary

End point timeframe

Baseline (of previous study part) and week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	27	30	17	24	60	49
Units: Score on a Scale
median (full range (min-max))	-1.940 (-2.11 to -0.42)	-1.970 (-2.07 to -0.95)	-1.76 (-2.1 to -1.0)	-1.96 (-2.1 to -1.5)	-1.95 (-2.1 to 0.3)	-1.97 (-2.2 to -0.7)

No statistical analyses for this end point

Secondary: Concentration of functional dupilumab in serum at week 52

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End point title

Concentration of functional dupilumab in serum at week 52

End point description

The PK analysis set (PKAS) for Part A and Part C included all randomized participants who received any study drug and who had at least one non-missing drug concentration result following the first dose of study drug in the corresponding study part. The PKAS for Part B and Part C included all randomized participants who received any study drug and who had at least one non-missing drug concentration result following the first dose of study drug in the corresponding study part.

End point type

Secondary

End point timeframe

Baseline (of Part C) up to week 52

End point values	Part A/C: Placebo / Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	34	38	36	37	77	69
Units: milligrams per liter (mg/L)
arithmetic mean (standard deviation)
Week 24 (n=32,36,35,37,73,64)	0 ± 0	193 ± 71.4	0 ± 0	1.21 ± 7.33	74.6 ± 45.5	199 ± 92.7
Week 32 (n=28,24,31,35,71,58)	101 ± 44.6	205 ± 76.8	46.0 ± 33.1	124 ± 56.7	74.0 ± 42.0	195 ± 94.6
Week 52 (n=30,37,33,37,73,66)	137 ± 81.6	152 ± 70.2	58.6 ± 36.5	151 ± 96.0	68.9 ± 45.7	176 ± 120

No statistical analyses for this end point

Secondary: Incidence of treatment-emergent anti-drug antibody (ADA) response

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End point title

Incidence of treatment-emergent anti-drug antibody (ADA) response

End point description

Number of treatment-emergent ADA responses to dupilumab reported. The ADA analysis set (AAS) for Part A and Part C included all participants who received any study drug and had at least one non-missing ADA result from the dupilumab ADA assay after first dose of the study drug in the corresponding study part (participants analyzed according to treatment actually received). The AAS for Part B and Part C included all participants who received any study drug and had at least one non-missing ADA result from the dupilumab ADA assay after first dose of the study drug in the corresponding study part (participants analyzed according to treatment actually received)..

End point type

Secondary

End point timeframe

Baseline (of previous study part) up to week 52

End point values	Part A: Placebo	Part A/C: Placebo / Dupilumab 300 mg QW	Part A: Dupilumab 300 mg QW	Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW	Part B: Placebo	Part B/C: Placebo / Dupilumab 300 mg Q2W	Part B: Dupilumab 300 mg Q2W	Part B/C: Placebo / Dupilumab 300 mg QW	Part B: Dupilumab 300 mg QW	Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W	Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW
Number of subjects analysed	39	35	42	39	77	36	77	37	76	77	69
Units: Events
number (not applicable)	0	4	0	1	0	1	2	0	1	5	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From day of first dose up to 12 weeks after end of treatment visit

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Part A: Placebo

Reporting group description

Participants received placebo matching dupilumab SC during Part A (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part A entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Reporting group title

Part B: Placebo

Reporting group description

Reporting group title

Part B: Dupilumab 300 mg Q2W

Reporting group description

Participants received dupilumab 300 mg Q2W SC during Part B (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part B entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Reporting group title

Part A: Dupilumab 300 mg QW

Reporting group description

Participants received dupilumab 300 mg SC QW during Part A (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part A entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Reporting group title

Part B: Dupilumab 300 mg QW

Reporting group description

Participants received dupilumab 300 mg SC QW during Part B (24-week DBTP). At end of week 24 visit (one-week after last dose of study drug during DBTP), eligible participants from Part B entered into 28-week extended treatment (Part C) and 12-week follow-up. Participants who did not enter into Part C, entered follow-up period.

Reporting group title

Part C: Dupilumab 300 mg Q2W (placebo in Part B)

Reporting group description

Reporting group title

Part C: Dupilumab 300 mg QW (placebo in Part A or B)

Reporting group description

Participants randomized to placebo in Part A, received dupilumab 300 mg QW for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up. Participants randomized to placebo in Part B were re-randomized in a 1:1 ratio to receive dupilumab 300 mg Q2W for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Reporting group title

Part C: Dupilumab 300 mg Q2W (Part B regimen continued)

Reporting group description

Reporting group title

Part C: Dupilumab 300 mg QW (Part A or B regimen continued)

Reporting group description

Participants randomized to dupilumab 300 mg QW in Part A continued to receive the same regimen for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up. Participants randomized to dupilumab 300 mg QW during Part B, continued to receive the same regimen for 28-week extended treatment (Part C) followed by 12-week follow-up. Participants who did not enter into Part C, entered follow-up.

Serious adverse events	Part A: Placebo	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part A: Dupilumab 300 mg QW	Part B: Dupilumab 300 mg QW	Part C: Dupilumab 300 mg Q2W (placebo in Part B)	Part C: Dupilumab 300 mg QW (placebo in Part A or B)	Part C: Dupilumab 300 mg Q2W (Part B regimen continued)	Part C: Dupilumab 300 mg QW (Part A or B regimen continued)
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 39 (5.13%)	1 / 78 (1.28%)	2 / 81 (2.47%)	2 / 42 (4.76%)	5 / 80 (6.25%)	1 / 37 (2.70%)	3 / 74 (4.05%)	1 / 79 (1.27%)	4 / 114 (3.51%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Investigations
Blood creatine phosphokinase abnormal
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Open globe injury
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	1 / 37 (2.70%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 39 (2.56%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 74 (1.35%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	1 / 42 (2.38%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 74 (1.35%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal tenesmus
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine polyp
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	1 / 42 (2.38%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 39 (2.56%)	0 / 78 (0.00%)	2 / 81 (2.47%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression suicidal
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	0 / 39 (0.00%)	1 / 78 (1.28%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised anxiety disorder
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	1 / 79 (1.27%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Substance use disorder
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	1 / 79 (1.27%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Campylobacter colitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	1 / 80 (1.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 74 (1.35%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis infectious
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A: Placebo	Part B: Placebo	Part B: Dupilumab 300 mg Q2W	Part A: Dupilumab 300 mg QW	Part B: Dupilumab 300 mg QW	Part C: Dupilumab 300 mg Q2W (placebo in Part B)	Part C: Dupilumab 300 mg QW (placebo in Part A or B)	Part C: Dupilumab 300 mg Q2W (Part B regimen continued)	Part C: Dupilumab 300 mg QW (Part A or B regimen continued)
Total subjects affected by non serious adverse events
subjects affected / exposed	28 / 39 (71.79%)	41 / 78 (52.56%)	57 / 81 (70.37%)	26 / 42 (61.90%)	50 / 80 (62.50%)	19 / 37 (51.35%)	44 / 74 (59.46%)	47 / 79 (59.49%)	62 / 114 (54.39%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	2 / 39 (5.13%)	1 / 78 (1.28%)	1 / 81 (1.23%)	0 / 42 (0.00%)	3 / 80 (3.75%)	4 / 37 (10.81%)	3 / 74 (4.05%)	2 / 79 (2.53%)	2 / 114 (1.75%)
occurrences all number	2	1	1	0	3	6	3	2	3
Injury, poisoning and procedural complications
Vaccination complication
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	2 / 80 (2.50%)	0 / 37 (0.00%)	1 / 74 (1.35%)	4 / 79 (5.06%)	2 / 114 (1.75%)
occurrences all number	0	0	0	0	2	0	1	4	2
Vascular disorders
Hypertension
subjects affected / exposed	0 / 39 (0.00%)	1 / 78 (1.28%)	1 / 81 (1.23%)	1 / 42 (2.38%)	4 / 80 (5.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	1 / 79 (1.27%)	2 / 114 (1.75%)
occurrences all number	0	1	1	1	5	0	0	1	2
Nervous system disorders
Headache
subjects affected / exposed	4 / 39 (10.26%)	9 / 78 (11.54%)	5 / 81 (6.17%)	2 / 42 (4.76%)	7 / 80 (8.75%)	2 / 37 (5.41%)	4 / 74 (5.41%)	4 / 79 (5.06%)	5 / 114 (4.39%)
occurrences all number	11	28	10	7	8	6	9	6	8
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	6 / 39 (15.38%)	9 / 78 (11.54%)	18 / 81 (22.22%)	4 / 42 (9.52%)	8 / 80 (10.00%)	2 / 37 (5.41%)	6 / 74 (8.11%)	6 / 79 (7.59%)	10 / 114 (8.77%)
occurrences all number	22	42	93	12	25	32	13	36	21
Injection site reaction
subjects affected / exposed	5 / 39 (12.82%)	16 / 78 (20.51%)	18 / 81 (22.22%)	9 / 42 (21.43%)	16 / 80 (20.00%)	3 / 37 (8.11%)	12 / 74 (16.22%)	14 / 79 (17.72%)	14 / 114 (12.28%)
occurrences all number	19	69	75	45	84	4	40	50	101
Injection site pain
subjects affected / exposed	3 / 39 (7.69%)	4 / 78 (5.13%)	10 / 81 (12.35%)	5 / 42 (11.90%)	7 / 80 (8.75%)	4 / 37 (10.81%)	6 / 74 (8.11%)	6 / 79 (7.59%)	9 / 114 (7.89%)
occurrences all number	6	21	45	9	39	34	7	66	45
Injection site oedema
subjects affected / exposed	2 / 39 (5.13%)	3 / 78 (3.85%)	4 / 81 (4.94%)	2 / 42 (4.76%)	0 / 80 (0.00%)	0 / 37 (0.00%)	3 / 74 (4.05%)	3 / 79 (3.80%)	3 / 114 (2.63%)
occurrences all number	2	7	4	7	0	0	12	12	8
Injection site pruritus
subjects affected / exposed	2 / 39 (5.13%)	3 / 78 (3.85%)	1 / 81 (1.23%)	1 / 42 (2.38%)	4 / 80 (5.00%)	1 / 37 (2.70%)	1 / 74 (1.35%)	3 / 79 (3.80%)	0 / 114 (0.00%)
occurrences all number	2	5	6	1	5	6	1	8	0
Injection site bruising
subjects affected / exposed	1 / 39 (2.56%)	0 / 78 (0.00%)	6 / 81 (7.41%)	1 / 42 (2.38%)	0 / 80 (0.00%)	1 / 37 (2.70%)	4 / 74 (5.41%)	1 / 79 (1.27%)	3 / 114 (2.63%)
occurrences all number	2	0	7	2	0	4	4	4	3
Injection site swelling
subjects affected / exposed	1 / 39 (2.56%)	2 / 78 (2.56%)	7 / 81 (8.64%)	5 / 42 (11.90%)	10 / 80 (12.50%)	4 / 37 (10.81%)	0 / 74 (0.00%)	2 / 79 (2.53%)	4 / 114 (3.51%)
occurrences all number	5	10	12	7	25	4	0	4	27
Pyrexia
subjects affected / exposed	1 / 39 (2.56%)	1 / 78 (1.28%)	3 / 81 (3.70%)	2 / 42 (4.76%)	5 / 80 (6.25%)	0 / 37 (0.00%)	0 / 74 (0.00%)	1 / 79 (1.27%)	2 / 114 (1.75%)
occurrences all number	1	1	3	2	5	0	0	1	2
Fatigue
subjects affected / exposed	0 / 39 (0.00%)	4 / 78 (5.13%)	2 / 81 (2.47%)	1 / 42 (2.38%)	5 / 80 (6.25%)	1 / 37 (2.70%)	1 / 74 (1.35%)	1 / 79 (1.27%)	2 / 114 (1.75%)
occurrences all number	0	20	2	1	5	1	1	1	2
Injection site urticaria
subjects affected / exposed	0 / 39 (0.00%)	2 / 78 (2.56%)	6 / 81 (7.41%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	2 / 79 (2.53%)	0 / 114 (0.00%)
occurrences all number	0	4	9	0	0	0	0	5	0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	1 / 81 (1.23%)	0 / 42 (0.00%)	0 / 80 (0.00%)	2 / 37 (5.41%)	0 / 74 (0.00%)	1 / 79 (1.27%)	2 / 114 (1.75%)
occurrences all number	0	0	1	0	0	2	0	1	2
Gastrointestinal disorders
Nausea
subjects affected / exposed	3 / 39 (7.69%)	7 / 78 (8.97%)	4 / 81 (4.94%)	1 / 42 (2.38%)	5 / 80 (6.25%)	2 / 37 (5.41%)	1 / 74 (1.35%)	2 / 79 (2.53%)	4 / 114 (3.51%)
occurrences all number	4	7	4	2	5	3	1	2	4
Abdominal pain
subjects affected / exposed	2 / 39 (5.13%)	4 / 78 (5.13%)	2 / 81 (2.47%)	1 / 42 (2.38%)	4 / 80 (5.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	2 / 79 (2.53%)	4 / 114 (3.51%)
occurrences all number	3	4	2	1	4	0	0	2	4
Diarrhoea
subjects affected / exposed	2 / 39 (5.13%)	8 / 78 (10.26%)	3 / 81 (3.70%)	2 / 42 (4.76%)	1 / 80 (1.25%)	2 / 37 (5.41%)	2 / 74 (2.70%)	2 / 79 (2.53%)	0 / 114 (0.00%)
occurrences all number	2	12	4	2	1	2	2	2	0
Dysphagia
subjects affected / exposed	2 / 39 (5.13%)	0 / 78 (0.00%)	1 / 81 (1.23%)	0 / 42 (0.00%)	2 / 80 (2.50%)	1 / 37 (2.70%)	1 / 74 (1.35%)	4 / 79 (5.06%)	4 / 114 (3.51%)
occurrences all number	2	0	1	0	2	1	2	4	4
Vomiting
subjects affected / exposed	1 / 39 (2.56%)	4 / 78 (5.13%)	3 / 81 (3.70%)	2 / 42 (4.76%)	3 / 80 (3.75%)	1 / 37 (2.70%)	3 / 74 (4.05%)	2 / 79 (2.53%)	4 / 114 (3.51%)
occurrences all number	1	6	5	2	3	1	4	2	4
Dyspepsia
subjects affected / exposed	0 / 39 (0.00%)	4 / 78 (5.13%)	2 / 81 (2.47%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	4 / 74 (5.41%)	2 / 79 (2.53%)	4 / 114 (3.51%)
occurrences all number	0	9	2	0	0	0	6	2	6
Eosinophilic oesophagitis
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	4 / 37 (10.81%)	0 / 74 (0.00%)	0 / 79 (0.00%)	0 / 114 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	2 / 39 (5.13%)	6 / 78 (7.69%)	5 / 81 (6.17%)	0 / 42 (0.00%)	4 / 80 (5.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	2 / 79 (2.53%)	1 / 114 (0.88%)
occurrences all number	2	7	6	0	4	0	0	2	1
Rhinitis allergic
subjects affected / exposed	2 / 39 (5.13%)	2 / 78 (2.56%)	1 / 81 (1.23%)	1 / 42 (2.38%)	2 / 80 (2.50%)	0 / 37 (0.00%)	3 / 74 (4.05%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences all number	2	2	1	1	2	0	3	0	1
Rhinorrhoea
subjects affected / exposed	0 / 39 (0.00%)	0 / 78 (0.00%)	0 / 81 (0.00%)	3 / 42 (7.14%)	0 / 80 (0.00%)	0 / 37 (0.00%)	0 / 74 (0.00%)	0 / 79 (0.00%)	1 / 114 (0.88%)
occurrences all number	0	0	0	3	0	0	0	0	1
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	4 / 39 (10.26%)	1 / 78 (1.28%)	0 / 81 (0.00%)	0 / 42 (0.00%)	0 / 80 (0.00%)	0 / 37 (0.00%)	1 / 74 (1.35%)	1 / 79 (1.27%)	2 / 114 (1.75%)
occurrences all number	5	1	0	0	0	0	1	1	2
Rash
subjects affected / exposed	4 / 39 (10.26%)	0 / 78 (0.00%)	4 / 81 (4.94%)	0 / 42 (0.00%)	3 / 80 (3.75%)	1 / 37 (2.70%)	0 / 74 (0.00%)	2 / 79 (2.53%)	7 / 114 (6.14%)
occurrences all number	4	0	4	0	3	1	0	2	9
Acne
subjects affected / exposed	1 / 39 (2.56%)	3 / 78 (3.85%)	2 / 81 (2.47%)	0 / 42 (0.00%)	0 / 80 (0.00%)	2 / 37 (5.41%)	4 / 74 (5.41%)	2 / 79 (2.53%)	2 / 114 (1.75%)
occurrences all number	1	3	3	0	0	2	4	2	2
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 39 (0.00%)	1 / 78 (1.28%)	2 / 81 (2.47%)	0 / 42 (0.00%)	3 / 80 (3.75%)	1 / 37 (2.70%)	4 / 74 (5.41%)	1 / 79 (1.27%)	4 / 114 (3.51%)
occurrences all number	0	1	2	0	3	1	4	1	5
Infections and infestations
Nasopharyngitis
subjects affected / exposed	4 / 39 (10.26%)	3 / 78 (3.85%)	4 / 81 (4.94%)	5 / 42 (11.90%)	2 / 80 (2.50%)	2 / 37 (5.41%)	7 / 74 (9.46%)	2 / 79 (2.53%)	5 / 114 (4.39%)
occurrences all number	4	4	5	6	2	2	8	3	6
Sinusitis
subjects affected / exposed	2 / 39 (5.13%)	0 / 78 (0.00%)	0 / 81 (0.00%)	1 / 42 (2.38%)	4 / 80 (5.00%)	0 / 37 (0.00%)	2 / 74 (2.70%)	2 / 79 (2.53%)	1 / 114 (0.88%)
occurrences all number	2	0	0	1	5	0	2	2	1
COVID-19
subjects affected / exposed	1 / 39 (2.56%)	0 / 78 (0.00%)	5 / 81 (6.17%)	0 / 42 (0.00%)	4 / 80 (5.00%)	1 / 37 (2.70%)	7 / 74 (9.46%)	8 / 79 (10.13%)	10 / 114 (8.77%)
occurrences all number	1	0	5	0	4	1	7	8	10
Upper respiratory tract infection
subjects affected / exposed	0 / 39 (0.00%)	2 / 78 (2.56%)	2 / 81 (2.47%)	4 / 42 (9.52%)	3 / 80 (3.75%)	0 / 37 (0.00%)	2 / 74 (2.70%)	0 / 79 (0.00%)	6 / 114 (5.26%)
occurrences all number	0	2	2	4	4	0	2	0	7

More information

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Were there any global substantial amendments to the protocol? Yes

04 Oct 2018

Added an exclusion criterion: known systemic hypersensitivity to dupilumab or the excipients of the drug product; Exclusion Criterion # 26: replaced serum creatinine threshold with estimated glomerular filtration rate (eGFR); Exclusion Criterion #27: replaced the example for severe renal conditions of “patients on dialysis” with “severe nephrotic syndrome”; Exclusion Criterion #33: Added clarification that the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient based on Clinical Trial Facilitation Group guideline on contraception; Clarified criteria for resumption of treatment after study drug has been temporarily discontinued because of a severe laboratory abnormality.

18 Apr 2019

Per Health Authority request, changed Part C from open-label to a design with added placebo SC injections alternating with dupilumab 300 mg Q2W doses in order to mask the dosing regimen for Part B patients during this extended active treatment phase of the study; Added a per protocol set to the defined efficacy analysis sets to assess the overall robustness of the analysis results. Added that any re-estimation of sample size for Part B will be documented in the Part B SAP before its database lock. If the re-estimated sample size requires an increase of the planned sample size in Part B by more than 86 total patients (25%), it will also be documented in a protocol amendment so as to inform Has, ECs, and investigators; Added a substudy which may be performed at select sites and a secondary endpoint to the study for the endolumenal functional lumen imaging probe (EndoFLIP) procedure to measure esophageal distensibility during the esophagogastroscopy procedures at selected sites in approximately 150 adult patients; Added additional secondary endpoints for proportion of patients who receive rescue medications or procedures during the 24-week placebo-controlled treatment period and absolute change in EoE Stage Score from the EoEHSS from baseline to week 24.

10 Mar 2020

The purpose of this amendment was to add transcriptome sequencing for analyzing RNA expression of eosinophilic esophagitis (EoE) and type 2 inflammation to the study secondary objectives and endpoints, and to add the European Quality of Life 5-dimension 3-level (EQ-5D3L) Questionnaire to collect general health status of EoE patients. Additionally, the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) procedure for Part B patients was revised to allow for centralized reading and scoring. Other minor changes were made to align with regulatory authority feedback and for general clarification.

16 Apr 2020

The purpose of this protocol amendment was to protect patient safety and data integrity during the COVID-19 pandemic by allowing for certain study procedures to occur at delayed time points and/or outside of the clinic environment. All temporary mechanisms utilized, and deviations from planned study procedures are to be documented as being related to COVID-19 and will remain in effect only for the duration of the public health emergency.

05 Nov 2020

The purpose of this protocol amendment was to adjust the sample size for Part B based on the results of Part A of the study, and to add an additional database lock after all patients in Part A complete study week 52 of Part C. Other changes were made for clarification and consistency

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
27 Mar 2020	Enrollment was halted due to operational challenges associated with measures in place to limit the spread of the COVID-19 pandemic.	01 Jun 2020

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 Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 24

Primary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 24

Primary: Absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) total score at week 24

Primary: Absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) total score at week 24

Secondary: Percent change from baseline in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 24

Secondary: Percent change from baseline in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 24

Secondary: Percent change from baseline in DSQ total score at week 24

Secondary: Percent change from baseline in DSQ total score at week 24

Secondary: Absolute change from baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) mean Grade score at week 24

Secondary: Absolute change from baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) mean Grade score at week 24

Secondary: Absolute change from baseline in EoEHSS mean Stage score at week 24

Secondary: Absolute change from baseline in EoEHSS mean Stage score at week 24

Secondary: Absolute change from baseline in EoE Endoscopic Reference total Score (EoE-EREFS) at week 24

Secondary: Absolute change from baseline in EoE Endoscopic Reference total Score (EoE-EREFS) at week 24

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 24

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 24

Secondary: Normalized Enrichment Score (NES) for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 24

Secondary: Normalized Enrichment Score (NES) for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 24

Secondary: NES for the relative change from baseline in type 2 inflammation signature at week 24

Secondary: NES for the relative change from baseline in type 2 inflammation signature at week 24

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 24

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 24

Secondary: Absolute change from baseline in health-related quality of life (QOL) average score as measured by EoE Impact Questionnaire (EoE-IQ) at week 24

Secondary: Absolute change from baseline in health-related quality of life (QOL) average score as measured by EoE Impact Questionnaire (EoE-IQ) at week 24

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE Symptom Questionnaire (EoE-SQ) at week 24

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE Symptom Questionnaire (EoE-SQ) at week 24

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 24

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 24

Secondary: Percentage of participants who received rescue medication during the 24-week double-blind, placebo-controlled treatment period

Secondary: Percentage of participants who received rescue medication during the 24-week double-blind, placebo-controlled treatment period

Secondary: Concentration of functional dupilumab in serum at week 24

Secondary: Concentration of functional dupilumab in serum at week 24

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 52

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) in all three regions at week 52

Secondary: Absolute change in DSQ total score at week 52

Secondary: Absolute change in DSQ total score at week 52

Secondary: Percent change in DSQ total score at week 52

Secondary: Percent change in DSQ total score at week 52

Secondary: Absolute change in EoE-EREFS total score at week 52

Secondary: Absolute change in EoE-EREFS total score at week 52

Secondary: Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 52

Secondary: Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) in all three regions at week 52

Secondary: Absolute change in EoEHSS mean Grade score at week 52

Secondary: Absolute change in EoEHSS mean Grade score at week 52

Secondary: Absolute change in EoEHSS mean Stage score at week 52

Secondary: Absolute change in EoEHSS mean Stage score at week 52

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 52

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf in all three regions at week 52

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 52

Secondary: Percentage of participants achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf in all three regions at week 52

Secondary: Absolute change in health-related QOL average score as measured by EoE-IQ at week 52

Secondary: Absolute change in health-related QOL average score as measured by EoE-IQ at week 52

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Secondary: Absolute change from baseline in Severity of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Secondary: Absolute change from baseline in Frequency of EoE symptoms other than dysphagia as measured by EoE-SQ at week 52

Secondary: Percentage of participants who received rescue medication during the 28-week extended active treatment period

Secondary: Percentage of participants who received rescue medication during the 28-week extended active treatment period

Secondary: NES for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 52

Secondary: NES for the relative change from baseline in EoE Diagnostic Panel (EDP) at week 52

Secondary: NES for the relative change in type 2 inflammation signature at week 52

Secondary: NES for the relative change in type 2 inflammation signature at week 52

Secondary: Concentration of functional dupilumab in serum at week 52

Secondary: Concentration of functional dupilumab in serum at week 52

Secondary: Incidence of treatment-emergent anti-drug antibody (ADA) response

Secondary: Incidence of treatment-emergent anti-drug antibody (ADA) response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)