Eosinophilic Esophagitis
Conditions
Brief summary
The primary objective of the study is to assess the clinical efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, to relieve symptoms in adult participants with active, moderate to severe Eosinophilic Esophagitis (EoE). The secondary objectives of the study are: * To assess the safety, tolerability, and immunogenicity of SC doses of dupilumab in adult participants with active, moderate to severe EoE * To assess the effect of dupilumab on esophageal eosinophilic infiltration * To evaluate the pharmacokinetics (PK) of dupilumab in adult participants with EoE
Interventions
DRUGDupilumab
DRUGPlacebo
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: 1. Documented diagnosis of EoE by endoscopy prior to or at screening 2. History of on average at least 2 episodes of dysphagia (with intake of solids off anti-inflammatory therapy) per week in the 4 weeks prior to screening and on average at least 2 episodes of documented dysphagia per week in the weeks between screening and baseline; dysphagia is defined as trouble swallowing solid food, or having solid food stick, by participant report 3. Must remain on a stabilized diet for at least 6 weeks prior to screening and during the course of the study; stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups 4. Documented history of or presence of any of the following: allergic disease (e.g, allergic asthma, allergic rhinitis, atopic dermatitis (AD), or food allergies), peripheral eosinophil counts ≥0.25 GI/L, or serum total Immunoglobulin E (IgE) ≥100 kU/L Key
Exclusion criteria
1. Prior participation in a dupilumab (anti-IL-4R) clinical trial 2. Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis 3. History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery prior to screening 4. Any esophageal stricture unable to be passed with a standard, diagnostic, adult (9 to10 mm) upper endoscope or any critical esophageal stricture that requires dilation at screening 5. History of bleeding disorders or esophageal varices 6. Use of chronic aspirin, nonsteroidal agents, or anti-coagulants within 2 weeks prior to screening. Participants should not stop these agents solely to become eligible for entry into this study 7. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening 8. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 3 months prior to screening 9. Use of inhaled (pulmonary or nasal) topical corticosteroids within 3 months prior to screening and during the study, except stable dose for at least 3 months prior to screening biopsy, which cannot be changed during the study 10. Treatment with oral immunotherapy (OIT) within 6 months prior to screening 11. Allergen immunotherapy unless on stable dose for at least 1 year prior to screening 12. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study Note: The list of inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | Baseline, Week 10 | The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | Baseline, Week 12 | The SDI is a PRO used to determine frequency/intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
| Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | Baseline, Week 12 | The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
| Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10 | Baseline, Week 10 | The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
| Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12 | Baseline, Week 12 | The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
| Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | Baseline, Week 10 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
| Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | Baseline, Week 10 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
| Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | Baseline, Week 12 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
| Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | Baseline, Week 10 | The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms). |
| Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10 | Baseline, Week 10 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
| Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12 | Baseline, Week 12 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
| Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12 | Baseline, Week 12 | Peak eosinophils/high power field (eos/hpf) was determined by counting eosinophils in the most inflamed areas of each esophageal region sampled at each time point and calculating the change in the peak count at each site. |
| Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12 | Baseline, Week 12 | The EoE-EREFS includes a total of 6 major items related to the presence/ severity of esophageal features. Specific features scored by the investigator include rings (absent\[0\], mild\[1\], moderate\[2\], severe\[3\], not applicable); stricture (yes\[1\], no\[0\], not applicable); diameter of the stricture (if applicable; measurement not scored); exudates (absent\[0\], mild \[1\], severe\[2\]); furrows (absent\[0\], present\[1\]); edema (absent\[0\], present\[1\]). The total score of the 5 scored items ranges from 0 to 8 (higher score indicates worsening symptoms). |
| Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12 | Baseline, Week 12 | The EoE-QOL-A questionnaire includes 30 items related to 5 established domains (eating/diet impact, social impact, emotional impact, disease anxiety, and swallowing anxiety) of daily life experiences. The EoE-QOL-A has a 1-week recall period. The items are graded on a 5-point scale: 1 (Not at All), 2 (Slightly), 3 (Moderately), 4 (Quite a bit), and 5 (Extremely). The EoE-QOL-A score is the average obtained by dividing the total score by the number of questions (for participants without disease, 120/30 = 4). Total scores range from 1 to 5 (higher scores indicate worsening symptoms). |
| Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12 | Baseline through Week 12 | — |
| Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study | Baseline through Week 28 | Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during the on-treatment period (time from the first dose of study drug up to the end of study (Week 28). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participant hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. |
| Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | Baseline, Week 12 | The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods. |
Countries
United States
Participant flow
Recruitment details
A total of 80 participants were screened, of whom 47 were enrolled at 14 sites. Screen failures did not meet all inclusion criteria, met one or more exclusion criterion, or withdrew consent (33 participants). Of the 47 enrolled, 23 participants were randomized to receive dupilumab 300 mg QW and 24 participants were randomized to receive placebo.
Pre-assignment details
After providing informed consent, participants were assessed at screening (to occur between day -35 & day -1) for eligibility to participate in the study. Participants who met the eligibility criteria underwent day 1 baseline assessments & randomized in a 1:1 ratio to receive dupilumab or placebo during the 12-week double-blind treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo once weekly (qw) during the 12-week double-blind treatment phase. Participants received 2 injections on day 1, followed by weekly injections. | 24 |
| Dupilumab 300 mg QW Participants received subcutaneous (SC) dupilumab 300 mg during the 12-week double-blind treatment phase. Participants received 2 injections (300-mg initial dose, followed by a 300-mg loading dose) on day 1, followed by weekly injections. | 23 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Did Not Meet Inc./ Exclusion Criteria | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subject was Incarcerated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Dupilumab 300 mg QW |
|---|---|---|---|
| Adult Eosinophilic Esophagitis Quality of Life (EoE-QOL-A) Total Mean Score (1-5) | 3.11 Score on a Scale STANDARD_DEVIATION 0.995 | 3.06 Score on a Scale STANDARD_DEVIATION 0.94 | 3.02 Score on a Scale STANDARD_DEVIATION 0.899 |
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 12.75 | 34.7 Years STANDARD_DEVIATION 10.94 | 33.1 Years STANDARD_DEVIATION 8.7 |
| Age Group ≥18 to <40 years | 15 Count of Participants | 31 Count of Participants | 16 Count of Participants |
| Age Group ≥40 to <65 years | 9 Count of Participants | 16 Count of Participants | 7 Count of Participants |
| Age Group ≥65 years | 0 Count of Participants | 0 Count of Participants | 0 Count of Participants |
| Baseline Blood Peripheral Eosinophils (EOS) Number of participants with EOS < 0.25 Giga/L | 8 Count of Participants | 19 Count of Participants | 11 Count of Participants |
| Baseline Blood Peripheral Eosinophils (EOS) Number of participants with EOS ≥ 0.25 Giga/L | 16 Count of Participants | 28 Count of Participants | 12 Count of Participants |
| Baseline Blood Peripheral Eosinophils (EOS) | 0.43 Giga/Liter (L) STANDARD_DEVIATION 0.285 | 0.37 Giga/Liter (L) STANDARD_DEVIATION 0.242 | 0.31 Giga/Liter (L) STANDARD_DEVIATION 0.177 |
| Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) Total Score (0-8) | 4.3 Score on a Scale STANDARD_DEVIATION 1.46 | 4.1 Score on a Scale STANDARD_DEVIATION 1.67 | 3.9 Score on a Scale STANDARD_DEVIATION 1.87 |
| Number of Esophageal Dilations | 3.9 Count of Esophageal Dilations STANDARD_DEVIATION 3.31 | 4.9 Count of Esophageal Dilations STANDARD_DEVIATION 6.17 | 5.7 Count of Esophageal Dilations STANDARD_DEVIATION 8.03 |
| Peak Eosinophils/ High Power Field (eos/hpf) Count | 101.1 Count of Eosinophils STANDARD_DEVIATION 57.12 | 101.6 Count of Eosinophils STANDARD_DEVIATION 54.76 | 102.1 Count of Eosinophils STANDARD_DEVIATION 53.46 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 24 Participants | 47 Participants | 23 Participants |
| Sex: Female, Male Female | 14 Participants | 24 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 23 Participants | 13 Participants |
| Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) PRO Score (0-100) | 62.2 Score on a Scale STANDARD_DEVIATION 16.45 | 62.1 Score on a Scale STANDARD_DEVIATION 17.25 | 62.0 Score on a Scale STANDARD_DEVIATION 18.36 |
| Weekly Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Score (0-9) | 6.4 Score on a Scale STANDARD_DEVIATION 1.01 | 6.4 Score on a Scale STANDARD_DEVIATION 1.01 | 6.4 Score on a Scale STANDARD_DEVIATION 1.04 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 14 / 24 | 18 / 23 |
| serious Total, serious adverse events | 0 / 24 | 3 / 23 |
Outcome results
Primary
Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 10
Population: Full Analysis Set (FAS) included all randomized participants. Efficacy analyses were based on the treatment allocated by the interactive voice and web response system (IVRS/IWRS) at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | -1.3 Score on a Scale | Standard Error 0.57 |
| Dupilumab 300 mg QW | Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | -3.0 Score on a Scale | Standard Error 0.53 |
p-value: 0.030495% CI: [-3.22, -0.16]ANCOVA
Secondary
Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12
The EoE-EREFS includes a total of 6 major items related to the presence/ severity of esophageal features. Specific features scored by the investigator include rings (absent\[0\], mild\[1\], moderate\[2\], severe\[3\], not applicable); stricture (yes\[1\], no\[0\], not applicable); diameter of the stricture (if applicable; measurement not scored); exudates (absent\[0\], mild \[1\], severe\[2\]); furrows (absent\[0\], present\[1\]); edema (absent\[0\], present\[1\]). The total score of the 5 scored items ranges from 0 to 8 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12 | -0.3 Score on a Scale | Standard Error 0.33 |
| Dupilumab 300 mg QW | Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12 | -1.9 Score on a Scale | Standard Error 0.32 |
p-value: 0.000695% CI: [-2.5, -0.68]ANCOVA
Secondary
Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12
The SDI is a PRO used to determine frequency/intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | -2.2 Score on a Scale | Standard Error 0.69 |
| Dupilumab 300 mg QW | Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | -2.9 Score on a Scale | Standard Error 0.56 |
p-value: 0.38395% CI: [-2.48, 0.96]ANCOVA
Secondary
Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 10
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | -9.0 Score on a Scale | Standard Error 5.58 |
| Dupilumab 300 mg QW | Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | -22.9 Score on a Scale | Standard Error 5.01 |
p-value: 0.063595% CI: [-28.54, 0.78]ANCOVA
Secondary
Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | -5.0 Score on a Scale | Standard Error 7.06 |
| Dupilumab 300 mg QW | Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | -26.1 Score on a Scale | Standard Error 5.87 |
p-value: 0.031895% CI: [-40.42, -1.86]ANCOVA
Secondary
Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12
The EoE-QOL-A questionnaire includes 30 items related to 5 established domains (eating/diet impact, social impact, emotional impact, disease anxiety, and swallowing anxiety) of daily life experiences. The EoE-QOL-A has a 1-week recall period. The items are graded on a 5-point scale: 1 (Not at All), 2 (Slightly), 3 (Moderately), 4 (Quite a bit), and 5 (Extremely). The EoE-QOL-A score is the average obtained by dividing the total score by the number of questions (for participants without disease, 120/30 = 4). Total scores range from 1 to 5 (higher scores indicate worsening symptoms).
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12 | 0.47 Score on a Scale | Standard Error 0.141 |
| Dupilumab 300 mg QW | Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12 | 0.80 Score on a Scale | Standard Error 0.137 |
p-value: 0.09195% CI: [-0.053, 0.72]ANCOVA
Secondary
Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 10
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10 | 8.3 Percentage of Participants |
| Dupilumab 300 mg QW | Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10 | 26.1 Percentage of Participants |
p-value: 0.136595% CI: [-11.54, 43.55]Clopper-Pearson Exact
Secondary
Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12 | 4.2 Percentage of Participants |
| Dupilumab 300 mg QW | Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12 | 39.1 Percentage of Participants |
p-value: 0.004495% CI: [5.69, 58.34]Clopper-Pearson Exact
Secondary
Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10
The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 10
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10 | 12.5 Percentage of Participants |
| Dupilumab 300 mg QW | Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10 | 39.1 Percentage of Participants |
p-value: 0.04995% CI: [-3.04, 51.05]Clopper-Pearson Exact
Secondary
Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12
The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12 | 12.5 Percentage of Participants |
| Dupilumab 300 mg QW | Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12 | 39.1 Percentage of Participants |
p-value: 0.04995% CI: [-3.04, 51.05]Clopper-Pearson Exact
Secondary
Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12
Time frame: Baseline through Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12 | 0 Percent of Participants |
| Dupilumab 300 mg QW | Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12 | 0 Percent of Participants |
Secondary
Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12
Peak eosinophils/high power field (eos/hpf) was determined by counting eosinophils in the most inflamed areas of each esophageal region sampled at each time point and calculating the change in the peak count at each site.
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12 | 14.23 Percent Change | Standard Error 12.495 |
| Dupilumab 300 mg QW | Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12 | -92.90 Percent Change | Standard Error 12.068 |
p-value: <0.000195% CI: [-141.215, -73.046]ANCOVA
Secondary
Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 10
Population: Full analysis set (FAS) included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | -18.59 Percent Change | Standard Error 8.978 |
| Dupilumab 300 mg QW | Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 | -45.05 Percent Change | Standard Error 8.435 |
p-value: 0.031295% CI: [-50.523, -2.387]ANCOVA
Secondary
Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12
The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | -31.83 Percent Change | Standard Error 10.674 |
| Dupilumab 300 mg QW | Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 | -42.83 Percent Change | Standard Error 8.573 |
p-value: 0.414795% CI: [-37.46, 15.467]ANCOVA
Secondary
Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 10
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | -11.33 Percent Change | Standard Error 9.915 |
| Dupilumab 300 mg QW | Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 | -34.56 Percent Change | Standard Error 9.076 |
p-value: 0.08595% CI: [-49.677, 3.212]ANCOVA
Secondary
Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12
The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.
Time frame: Baseline, Week 12
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated by the IVRS/IWRS at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | -3.34 Percent Change | Standard Error 12.701 |
| Dupilumab 300 mg QW | Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 | -36.99 Percent Change | Standard Error 11.168 |
p-value: 0.060895% CI: [-68.828, 1.536]ANCOVA
Secondary
Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study
Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during the on-treatment period (time from the first dose of study drug up to the end of study (Week 28). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participant hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time frame: Baseline through Week 28
Population: The safety analysis set (SAF) included all randomized participants who received any study drug, and were analyzed as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study | 66.7 Percent of Participants |
| Dupilumab 300 mg QW | Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study | 91.3 Percent of Participants |