A Randomized, Double-Blind, Parallel, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Dupilumab in Adult Patients With Active Eosinophilic Esophagitis
Overview
- Phase
- Phase 2
- Intervention
- Dupilumab
- Conditions
- Eosinophilic Esophagitis
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 47
- Primary Endpoint
- Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •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
Arms & Interventions
Dupilumab 300 mg QW
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.
Intervention: Dupilumab
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
Time Frame: 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 Outcomes
- 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)
- Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12(Baseline, Week 12)
- Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10(Baseline, Week 10)
- Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12(Baseline, Week 12)
- Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12(Baseline, Week 12)
- 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)
- 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)
- Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10(Baseline, Week 10)
- Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12(Baseline, Week 12)
- Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10(Baseline, Week 10)
- Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12(Baseline, Week 12)
- Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12(Baseline, Week 12)
- Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study(Baseline through Week 28)
- 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)
- Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12(Baseline, Week 12)
- Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12(Baseline through Week 12)