Study of Dupilumab in Adult Participants With Active Eosinophilic Esophagitis (EoE)
- Registration Number
- NCT02379052
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47
Not provided
- Prior participation in a dupilumab (anti-IL-4R) clinical trial
- Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis
- History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery prior to screening
- 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
- History of bleeding disorders or esophageal varices
- 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
- Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening
- Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 3 months prior to screening
- 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
- Treatment with oral immunotherapy (OIT) within 6 months prior to screening
- Allergen immunotherapy unless on stable dose for at least 1 year prior to screening
- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
Note: The list of inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab 300 mg QW Dupilumab Participants received 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. Placebo 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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).
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).
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 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 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.
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.
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.
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).
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.
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.
Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12 Baseline through Week 12