Eosinophilic Esophagitis
Conditions
Brief summary
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
Interventions
DRUGDupilumab
Solution for injection administered subcutaneously
DRUGPlacebo
Matching placebo
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria (Parts A & B): * A documented diagnosis of EoE by endoscopic biopsy * Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration * History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening Key
Exclusion criteria
(Parts A & B): * Body weight ≤40 kg * Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab * Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening. * Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) * Active Helicobacter pylori infection * History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery * Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening * History of bleeding disorders or esophageal varices * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | Baseline and 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. |
| Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | Baseline and 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. |
| Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | Baseline and 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. |
| Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | At week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | Baseline and 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). |
| NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | Baseline and 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). |
| Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | At week 24 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | Baseline and 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. |
| Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | Baseline and 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. |
| Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | Baseline and 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. |
| Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | At week 24 | — |
| Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24 | 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 | At week 52 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | Baseline (of previous study part) and 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. |
| Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | Baseline and 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. |
| Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | Baseline (of previous study part) and 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. |
| Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | Baseline (of previous study part) and 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. |
| Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | Baseline (of previous study part) and 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. |
| Absolute Change in EoEHSS Mean Stage Score at Week 52 | Baseline (of previous study part) and 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. |
| Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | At week 52 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | At week 52 | Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). |
| Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | Baseline (of previous study part) and 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. |
| Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | Baseline (of previous study part) and 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. |
| Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | Baseline (of previous study part) and 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. |
| Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | Baseline (of Part C) to week 28 | — |
| NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | Baseline (of previous study part) and 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). |
| NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | Baseline (of previous study part) and 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). |
| Concentration of Functional Dupilumab in Serum at Week 52 | Baseline (of Part C) up to week 52 | — |
| Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | Baseline (of previous study part) up to week 52 | Number of treatment-emergent ADA responses to dupilumab reported. |
| Percent Change in DSQ Total Score at Week 52 | Baseline (of previous study part) and 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. |
| Percent Change From Baseline in DSQ Total Score at Week 24 | Baseline and 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. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
Part A (24-week 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).
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Participants received placebo matching dupilumab subcutaneously (SC) during Part A (a 24-week double-blind treatment period \[DBTP\]). At end of double-blind treatment visit, week 24 (one-week after last dose of study drug during the DBTP), eligible participants may enter into Part C. Participants who do not enter Part C will enter a 12-week follow-up period. | 39 |
| Part A: Dupilumab 300 mg SC QW Participants received dupilumab 300 milligrams (mg) SC once per week (QW) during Part A (a 24-week DBTP). At end of double-blind treatment visit, week 24 (one-week after last dose of study drug during the DBTP), eligible participants may enter into Part C. Participants who do not enter Part C will enter a 12-week follow-up period. | 42 |
| Part B: Placebo Participants received placebo matching dupilumab SC during Part B (a 24-week DBTP). At end of double-blind treatment visit, week 24 (one-week after last dose of study drug during the DBTP), eligible participants may enter into Part C. Participants who do not enter Part C will enter a 12-week follow-up period. | 79 |
| Part B: Dupilumab 300 mg SC Q2W Participants received dupilumab 300 mg once every 2 weeks (Q2W) SC during Part B (a 24-week DBTP). At end of double-blind treatment visit, week 24 (one-week after last dose of study drug during the DBTP), eligible participants may enter into Part C. Participants who do not enter Part C will enter a 12-week follow-up period. | 81 |
| Part B: Dupilumab 300 mg SC QW Participants received dupilumab 300 milligrams (mg) SC once per week (QW) during Part B (a 24-week DBTP). At end of double-blind treatment visit, week 24 (one-week after last dose of study drug during the DBTP), eligible participants may enter into Part C. Participants who do not enter Part C will enter a 12-week follow-up period. | 80 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A | Unconfirmed early termination visit | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A | Week 24 not performed due to Coronavirus Disease-2019 (COVID-19) | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Adverse Event | 0 | 0 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | COVID-19 Restrictions | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Subject randomized, but did not receive study drug; did not qualify for study | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part C (& Follow-up) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Part C (& Follow-up) | COVID-19 related | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part C (& Follow-up) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part C (& Follow-up) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 1 | 0 | 7 | 2 |
| Part C (& Follow-up) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Part C (& Follow-up) | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part C (& Follow-up) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 |
| Part C (& Follow-up) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 1 | 1 | 6 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: Dupilumab 300 mg SC QW | Total | Part B: Placebo | Part B: Dupilumab 300 mg SC Q2W | Part B: Dupilumab 300 mg SC QW |
|---|---|---|---|---|---|---|
| Age, Customized ≥ 12 to < 18 years old | 9 Participants | 11 Participants | 79 Participants | 26 Participants | 27 Participants | 26 Participants |
| Age, Customized ≥ 18 to < 40 years old | 22 Participants | 13 Participants | 111 Participants | 38 Participants | 35 Participants | 38 Participants |
| Age, Customized ≥ 40 to < 65 years old | 8 Participants | 18 Participants | 48 Participants | 15 Participants | 18 Participants | 15 Participants |
| Age, Customized ≥ 65 years old | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 38 Participants | 76 Participants | 74 Participants | 77 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Part A: Dysphagia Symptom Questionnaire (DSQ) Total Score | 35.1 Score on a Scale STANDARD_DEVIATION 12.11 | 32.2 Score on a Scale STANDARD_DEVIATION 12.66 | 33.6 Score on a Scale STANDARD_DEVIATION 12.41 | — | — | — |
| Part A: Eosinophilic Esophagitis (EoE) Histological Grade Calculated Mean Score (0 - 3) | 1.324 Score on a Scale STANDARD_DEVIATION 0.4676 | 1.260 Score on a Scale STANDARD_DEVIATION 0.4088 | 1.291 Score on a Scale STANDARD_DEVIATION 0.4365 | — | — | — |
| Part A: Eosinophilic Esophagitis (EoE) Histological Stage Calculated Mean Score (0 - 3) | 1.376 Score on a Scale STANDARD_DEVIATION 0.3972 | 1.299 Score on a Scale STANDARD_DEVIATION 0.3334 | 1.336 Score on a Scale STANDARD_DEVIATION 0.3653 | — | — | — |
| Part A: Peak Eosinophils (eos) Count of Three Regions per High-power Field (/hpf) | 96.5 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 54.69 | 82.6 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 41.02 | 89.3 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 48.29 | — | — | — |
| Part B: Dysphagia Symptom Questionnaire (DSQ) Total Score | — | — | 36.7 Score on a Scale STANDARD_DEVIATION 11.22 | 36.1 Score on a Scale STANDARD_DEVIATION 10.55 | 35.6 Score on a Scale STANDARD_DEVIATION 12.24 | 38.4 Score on a Scale STANDARD_DEVIATION 10.7 |
| Part B: Eosinophilic Esophagitis (EoE) Histological Grade Calculated Mean Score (0 - 3) | — | — | 1.259 Score on a Scale STANDARD_DEVIATION 0.3865 | 1.226 Score on a Scale STANDARD_DEVIATION 0.3996 | 1.245 Score on a Scale STANDARD_DEVIATION 0.3721 | 1.305 Score on a Scale STANDARD_DEVIATION 0.3882 |
| Part B: Eosinophilic Esophagitis (EoE) Histological Stage Calculated Mean Score (0 - 3) | — | — | 1.253 Score on a Scale STANDARD_DEVIATION 0.3353 | 1.216 Score on a Scale STANDARD_DEVIATION 0.3608 | 1.248 Score on a Scale STANDARD_DEVIATION 0.3182 | 1.294 Score on a Scale STANDARD_DEVIATION 0.3256 |
| Part B: Peak Eosinophils (eos) Count of Three Regions per High-power Field (/hpf) | — | — | 87.1 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 45.76 | 84.3 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 41.2 | 87.7 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 49.37 | 89.2 Eosinophils/high-power field (eos/hpf) STANDARD_DEVIATION 46.67 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 8 Participants | 3 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 37 Participants | 41 Participants | 217 Participants | 72 Participants | 74 Participants | 71 Participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 32 Participants | 21 Participants | 36 Participants | 30 Participants |
| Sex: Female, Male Male | 21 Participants | 28 Participants | 49 Participants | 58 Participants | 45 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 42 | 0 / 78 | 0 / 81 | 0 / 80 | 0 / 37 | 0 / 74 | 0 / 79 | 0 / 114 |
| other Total, other adverse events | 28 / 39 | 26 / 42 | 41 / 78 | 57 / 81 | 50 / 80 | 19 / 37 | 44 / 74 | 47 / 79 | 62 / 114 |
| serious Total, serious adverse events | 2 / 39 | 2 / 42 | 1 / 78 | 2 / 81 | 5 / 80 | 1 / 37 | 3 / 74 | 1 / 79 | 4 / 114 |
Outcome results
Primary
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
Population: Part A Full Analysis Set (FAS): All participant randomized to Part A (MI method with data set to missing after rescue treatment use); Part B FAS: All participants randomized to Part B (MI method with data set to missing after rescue treatment use)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | -9.60 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | -21.92 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | -13.86 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | -14.37 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 | -23.78 Score on a Scale |
p-value: 0.000495% CI: [-19.107, -5.537]ANCOVA
p-value: 0.839395% CI: [-5.423, 4.406]ANCOVA
p-value: <0.000195% CI: [-14.811, -5.022]ANCOVA
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
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 24
Population: 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); 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | 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 | 5.1 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | 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 | 59.5 Percentage of Participants |
| Part B: Placebo | 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 | 6.3 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | 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 | 60.5 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | 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 | 58.8 Percentage of Participants |
p-value: <0.000195% CI: [39.58, 71.04]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [43.44, 68.54]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [41.2, 65.79]Cochran-Mantel-Haenszel
Secondary
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
Population: Part A FAS (WOCF-MI Method With Data Set to Missing After Rescue Treatment Use); 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | -0.3 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | -3.2 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | -0.6 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | -4.6 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 | -4.5 Score on a Scale |
p-value: <0.000195% CI: [-3.91, -1.84]ANCOVA
p-value: <0.000195% CI: [-4.86, -3.02]ANCOVA
p-value: <0.000195% CI: [-4.77, -2.93]ANCOVA
Secondary
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
Population: Part A FAS (WOCF-MI Method With Data Set to Missing After Rescue Treatment Use); 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | -0.012 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | -0.753 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | -0.132 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | -0.793 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 | -0.804 Score on a Scale |
p-value: <0.000195% CI: [-0.8842, -0.5978]ANCOVA
p-value: <0.000195% CI: [-0.7674, -0.554]ANCOVA
p-value: <0.000195% CI: [-0.7778, -0.5655]ANCOVA
Secondary
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
Population: Part A FAS (WOCF-MI method with data set to missing after rescue treatment use); 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | -0.001 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | -0.761 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | -0.148 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | -0.814 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 | -0.830 Score on a Scale |
p-value: <0.000195% CI: [-0.9061, -0.6127]ANCOVA
p-value: <0.000195% CI: [-0.7773, -0.5538]ANCOVA
p-value: <0.000195% CI: [-0.7929, -0.5707]ANCOVA
Secondary
Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24
Time frame: At week 24
Population: Due to only 7 participants in Part B with change from baseline at week 24 data available across 3 treatment groups, results are not reported to protect the confidentiality of the participants.
Secondary
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
Population: 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | -1.7 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | -3.4 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | -2.6 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | -3.0 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 | -3.9 Score on a Scale |
p-value: 0.005195% CI: [-2.93, -0.52]ANCOVA
p-value: 0.315295% CI: [-1.38, 0.44]ANCOVA
p-value: 0.003795% CI: [-2.3, 0.45]ANCOVA
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -4.3 Score on a Scale | Standard Deviation 3.78 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -3.2 Score on a Scale | Standard Deviation 3.5 |
| Part B: Placebo | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -4.0 Score on a Scale | Standard Deviation 3.54 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -3.8 Score on a Scale | Standard Deviation 3.62 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -3.6 Score on a Scale | Standard Deviation 3.45 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -4.7 Score on a Scale | Standard Deviation 4.03 |
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
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
Population: 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | -0.246 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | -0.614 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | -0.578 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | -0.593 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24 | -0.887 Score on a Scale |
p-value: 0.007795% CI: [-0.6388, -0.0975]ANCOVA
p-value: 0.858695% CI: [-0.1782, 0.1485]ANCOVA
p-value: 0.000295% CI: [-0.4703, -0.1471]ANCOVA
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -7.2 Score on a Scale | Standard Deviation 6.46 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -5.9 Score on a Scale | Standard Deviation 6.8 |
| Part B: Placebo | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -6.2 Score on a Scale | Standard Deviation 6.42 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -5.9 Score on a Scale | Standard Deviation 6.47 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -4.7 Score on a Scale | Standard Deviation 5.99 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 | -6.4 Score on a Scale | Standard Deviation 6.86 |
Secondary
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
Population: 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | -3.9 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | -5.8 Score on a Scale |
| Part B: Placebo | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | -4.0 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | -4.5 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 | -5.4 Score on a Scale |
p-value: 0.046795% CI: [-3.87, -0.03]ANCOVA
p-value: 0.546995% CI: [-2.03, 1.08]ANCOVA
p-value: 0.071895% CI: [-3, 0.13]ANCOVA
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -21.71 Score on a Scale | Standard Deviation 17.143 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -23.44 Score on a Scale | Standard Deviation 16.149 |
| Part B: Placebo | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -23.69 Score on a Scale | Standard Deviation 13.737 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -27.25 Score on a Scale | Standard Deviation 11.457 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -20.87 Score on a Scale | Standard Deviation 16.387 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 | -30.26 Score on a Scale | Standard Deviation 15.389 |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -3.9 Score on a Scale | Standard Deviation 2.74 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -4.1 Score on a Scale | Standard Deviation 3.37 |
| Part B: Placebo | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -4.3 Score on a Scale | Standard Deviation 3.21 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -6.1 Score on a Scale | Standard Deviation 3.6 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -5.2 Score on a Scale | Standard Deviation 3.4 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -5.3 Score on a Scale | Standard Deviation 2.85 |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.873 Score on a Scale | Standard Deviation 0.5506 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.873 Score on a Scale | Standard Deviation 0.3537 |
| Part B: Placebo | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.779 Score on a Scale | Standard Deviation 0.4292 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.906 Score on a Scale | Standard Deviation 0.3936 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.838 Score on a Scale | Standard Deviation 0.4039 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 | -0.968 Score on a Scale | Standard Deviation 0.4293 |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.874 Score on a Scale | Standard Deviation 0.463 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.891 Score on a Scale | Standard Deviation 0.277 |
| Part B: Placebo | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.710 Score on a Scale | Standard Deviation 0.3783 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.871 Score on a Scale | Standard Deviation 0.351 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.809 Score on a Scale | Standard Deviation 0.3434 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change in EoEHSS Mean Stage Score at Week 52 | -0.932 Score on a Scale | Standard Deviation 0.373 |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -0.954 Score on a Scale | Standard Deviation 0.669 |
| Part A: Dupilumab 300 mg SC QW | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -0.911 Score on a Scale | Standard Deviation 0.6344 |
| Part B: Placebo | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -1.021 Score on a Scale | Standard Deviation 0.7169 |
| Part B: Dupilumab 300 mg SC Q2W | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -0.858 Score on a Scale | Standard Deviation 0.636 |
| Part B: Dupilumab 300 mg SC QW | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -0.773 Score on a Scale | Standard Deviation 0.6217 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 | -0.935 Score on a Scale | Standard Deviation 0.6883 |
Secondary
Concentration of Functional Dupilumab in Serum at Week 52
Time frame: Baseline (of Part C) up to week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 137 milligrams per liter (mg/L) | Standard Deviation 81.6 |
| Part A: Placebo | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 101 milligrams per liter (mg/L) | Standard Deviation 44.6 |
| Part A: Dupilumab 300 mg SC QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 152 milligrams per liter (mg/L) | Standard Deviation 70.2 |
| Part A: Dupilumab 300 mg SC QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 205 milligrams per liter (mg/L) | Standard Deviation 76.8 |
| Part B: Placebo | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 46.0 milligrams per liter (mg/L) | Standard Deviation 33.1 |
| Part B: Placebo | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 58.6 milligrams per liter (mg/L) | Standard Deviation 36.5 |
| Part B: Dupilumab 300 mg SC Q2W | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 124 milligrams per liter (mg/L) | Standard Deviation 56.7 |
| Part B: Dupilumab 300 mg SC Q2W | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 151 milligrams per liter (mg/L) | Standard Deviation 96 |
| Part B: Dupilumab 300 mg SC QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 74.0 milligrams per liter (mg/L) | Standard Deviation 42 |
| Part B: Dupilumab 300 mg SC QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 68.9 milligrams per liter (mg/L) | Standard Deviation 45.7 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 52 | 176 milligrams per liter (mg/L) | Standard Deviation 120 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Concentration of Functional Dupilumab in Serum at Week 52 | Week 32 | 195 milligrams per liter (mg/L) | Standard Deviation 94.6 |
Secondary
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
Population: ADA analysis set (AAS) Parts A \& C: All participants who received any study drug \& had at least 1 non-missing ADA result from dupilumab ADA assay after first dose of study drug in corresponding study part (according to treatment actually received); AAS Parts B \& C: All participants who received any study drug \& had at least 1 non-missing ADA result from dupilumab ADA assay after first dose of study drug in corresponding study part (according to treatment actually received).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Events |
| Part A: Dupilumab 300 mg SC QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Events |
| Part B: Placebo | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Events |
| Part B: Dupilumab 300 mg SC Q2W | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 2 Events |
| Part B: Dupilumab 300 mg SC QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 1 Events |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 4 Events |
| Part A/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 1 Events |
| Part B/C: Placebo / Dupilumab 300 mg Q2W | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 1 Events |
| Part B/C: Placebo / Dupilumab 300 mg QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Events |
| Part B/C: Dupilumab 300 mg Q2W / Dupilumab 300 mg Q2W | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 5 Events |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response | 0 Events |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Placebo | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.580 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.670 Score on a Scale |
| Part B: Placebo | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.28 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.62 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.64 Score on a Scale |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 | -2.69 Score on a Scale |
Secondary
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
Population: 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | -0.320 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | -1.970 Score on a Scale |
| Part B: Placebo | NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | -0.640 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | -1.950 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 | -1.930 Score on a Scale |
p-value: <0.000195% CI: [-1.74, -1.27]Wilcoxon rank-sum test
p-value: <0.000195% CI: [-1.73, -1.05]Wilcoxon rank-sum test
p-value: <0.000195% CI: [-1.82, -1.07]Wilcoxon rank-sum test
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Placebo | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.940 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.970 Score on a Scale |
| Part B: Placebo | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.76 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.96 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.95 Score on a Scale |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.97 Score on a Scale |
Secondary
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
Population: 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | -0.160 Score on a Scale |
| Part A: Dupilumab 300 mg SC QW | Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | -2.660 Score on a Scale |
| Part B: Placebo | Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | -0.730 Score on a Scale |
| Part B: Dupilumab 300 mg SC Q2W | Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | -2.675 Score on a Scale |
| Part B: Dupilumab 300 mg SC QW | Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 | -2.665 Score on a Scale |
p-value: <0.000195% CI: [-2.72, -1.73]Wilcoxon rank-sum test
p-value: <0.000195% CI: [-2.42, -1.11]Wilcoxon rank-sum test
p-value: <0.000195% CI: [-2.44, -1.15]Wilcoxon rank-sum test
Secondary
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
Population: Part A FAS (Participants considered non-responder after rescue treatment use and MI method for missing 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | 7.7 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | 64.3 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | 7.6 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | 79.0 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 | 82.5 Percentage of Participants |
p-value: <0.000195% CI: [41.69, 73.33]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [61.05, 83.7]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [64.25, 85.5]Cochran-Mantel-Haenszel
Secondary
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
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 70.0 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 82.4 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 87.5 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 78.4 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 83.6 Percentage of Participants |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 | 100 Percentage of Participants |
Secondary
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
Population: Part A FAS (Participants considered non-responder after rescue treatment use and MI method for missing 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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | 0.0 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | 21.4 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | 1.3 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | 27.2 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 | 28.8 Percentage of Participants |
p-value: 0.001795% CI: [9.42, 34.38]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [17.2, 38.09]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [18.36, 39.46]Cochran-Mantel-Haenszel
Secondary
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
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 26.7 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 29.4 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 40.6 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 16.2 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 31.5 Percentage of Participants |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 | 30.8 Percentage of Participants |
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
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
Time frame: At week 52
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | 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 | 60.0 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | 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 | 55.9 Percentage of Participants |
| Part B: Placebo | 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 | 71.9 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | 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 | 67.6 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | 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 | 74.0 Percentage of Participants |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | 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 | 84.6 Percentage of Participants |
Secondary
Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period
Time frame: Baseline (of Part C) to week 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 8.1 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 0 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 2.7 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 2.7 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 0 Percentage of Participants |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period | 1.4 Percentage of Participants |
Secondary
Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24
Time frame: At week 24
Population: Part A FAS; Part B FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | 12.8 Percentage of Participants |
| Part A: Dupilumab 300 mg SC QW | Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | 0.0 Percentage of Participants |
| Part B: Placebo | Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | 2.5 Percentage of Participants |
| Part B: Dupilumab 300 mg SC Q2W | Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | 1.2 Percentage of Participants |
| Part B: Dupilumab 300 mg SC QW | Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 | 2.5 Percentage of Participants |
p-value: 0.01795% CI: [-23.21, -2.26]Cochran-Mantel-Haenszel
p-value: 0.549395% CI: [-5.51, 2.93]Cochran-Mantel-Haenszel
p-value: 0.988795% CI: [-4.9, 5.02]Cochran-Mantel-Haenszel
Secondary
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
Population: 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Percent Change From Baseline in DSQ Total Score at Week 24 | -31.68 Percentage of Change |
| Part A: Dupilumab 300 mg SC QW | Percent Change From Baseline in DSQ Total Score at Week 24 | -69.17 Percentage of Change |
| Part B: Placebo | Percent Change From Baseline in DSQ Total Score at Week 24 | -41.43 Percentage of Change |
| Part B: Dupilumab 300 mg SC Q2W | Percent Change From Baseline in DSQ Total Score at Week 24 | -45.78 Percentage of Change |
| Part B: Dupilumab 300 mg SC QW | Percent Change From Baseline in DSQ Total Score at Week 24 | -64.32 Percentage of Change |
p-value: 0.000295% CI: [-57.222, -17.745]ANCOVA
p-value: 0.524395% CI: [-17.734, 9.038]ANCOVA
p-value: 0.000895% CI: [-36.272, -9.513]ANCOVA
Secondary
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
Population: Part A FAS (Worst-observation carried forward \[WOCF\]-MI method with data set to missing after rescue treatment use); 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)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | -2.98 Percentage of Change |
| Part A: Dupilumab 300 mg SC QW | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | -71.24 Percentage of Change |
| Part B: Placebo | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | 8.38 Percentage of Change |
| Part B: Dupilumab 300 mg SC Q2W | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | -70.84 Percentage of Change |
| Part B: Dupilumab 300 mg SC QW | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 | -80.24 Percentage of Change |
p-value: <0.000195% CI: [-86.896, -49.615]ANCOVA
p-value: <0.000195% CI: [-103.098, -55.338]ANCOVA
p-value: <0.000195% CI: [-112.194, -65.046]ANCOVA
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Percent Change in DSQ Total Score at Week 52 | -65.87 Percentage of Change | Standard Deviation 49.705 |
| Part A: Dupilumab 300 mg SC QW | Percent Change in DSQ Total Score at Week 52 | -75.93 Percentage of Change | Standard Deviation 36.892 |
| Part B: Placebo | Percent Change in DSQ Total Score at Week 52 | -71.01 Percentage of Change | Standard Deviation 37.256 |
| Part B: Dupilumab 300 mg SC Q2W | Percent Change in DSQ Total Score at Week 52 | -78.13 Percentage of Change | Standard Deviation 31.003 |
| Part B: Dupilumab 300 mg SC QW | Percent Change in DSQ Total Score at Week 52 | -61.19 Percentage of Change | Standard Deviation 44.447 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Percent Change in DSQ Total Score at Week 52 | -80.74 Percentage of Change | Standard Deviation 32.866 |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -83.76 Percentage of Change | Standard Deviation 24.996 |
| Part A: Dupilumab 300 mg SC QW | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -88.59 Percentage of Change | Standard Deviation 13.506 |
| Part B: Placebo | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -91.20 Percentage of Change | Standard Deviation 13.037 |
| Part B: Dupilumab 300 mg SC Q2W | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -84.21 Percentage of Change | Standard Deviation 42.169 |
| Part B: Dupilumab 300 mg SC QW | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -84.78 Percentage of Change | Standard Deviation 40.973 |
| Part B/C: Dupilumab 300 mg QW / Dupilumab 300 mg QW | Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 | -95.85 Percentage of Change | Standard Deviation 4.037 |