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. 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. The secondary objectives of the study are: * To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE * To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses * To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation * To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
321
Regeneron Study Site
Phoenix, Arizona, United States
Regeneron Study Site
Scottsdale, Arizona, United States
Regeneron Study Site
Little Rock, Arkansas, United States
Regeneron Study Site
La Jolla, California, United States
Regeneron Study Site
Los Angeles, California, United States
Regeneron Study Site
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
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 24
Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24
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.
Time frame: Baseline and week 24
Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24
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.
Time frame: Baseline and week 24
Percent Change From Baseline in DSQ Total Score at Week 24
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.
Time frame: Baseline and week 24
Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24
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.
Time frame: Baseline and week 24
Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24
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.
Time frame: Baseline and week 24
Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24
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.
Time frame: Baseline and week 24
Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 24
Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24
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).
Time frame: Baseline and week 24
NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24
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).
Time frame: Baseline and week 24
Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 24
Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24
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.
Time frame: Baseline and week 24
Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24
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.
Time frame: Baseline and week 24
Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24
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.
Time frame: Baseline and week 24
Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24
Time frame: At week 24
Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24
Time frame: At week 24
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
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 52
Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Percent Change in DSQ Total Score at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Absolute Change in EoEHSS Mean Stage Score at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 52
Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 52
Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52
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.
Time frame: Baseline (of previous study part) and week 52
Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period
Time frame: Baseline (of Part C) to week 28
NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52
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).
Time frame: Baseline (of previous study part) and week 52
NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52
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).
Time frame: Baseline (of previous study part) and week 52
Concentration of Functional Dupilumab in Serum at Week 52
Time frame: Baseline (of Part C) up to week 52
Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response
Number of treatment-emergent ADA responses to dupilumab reported.
Time frame: Baseline (of previous study part) up to week 52
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Orange, California, United States
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Aurora, Colorado, United States
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