Phase 3
N=81
Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
Eosinophilic Esophagitis
Bottom Line
View on ClinicalTrials.gov: NCT03633617 ↗Enrolled (actual)
81
Serious AEs
3.4%
Results posted
Dec 2022
Primary outcome: 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 — 5.1; 59.5; 6.3; 60.5 Percentage of Participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dupilumab (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Sep 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
5.1; 59.5; 6.3; 60.5; 58.8 | <0.0001 sig |
| PRIMARY Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 |
-9.60; -21.92; -13.86; -14.37; -23.78 | 0.0004 sig |
| SECONDARY Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24 |
-2.98; -71.24; 8.38; -70.84; -80.24 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in DSQ Total Score at Week 24 |
-31.68; -69.17; -41.43; -45.78; -64.32 | 0.0002 sig |
| SECONDARY Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24 |
-0.001; -0.761; -0.148; -0.814; -0.830 | <0.0001 sig |
| SECONDARY Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24 |
-0.012; -0.753; -0.132; -0.793; -0.804 | <0.0001 sig |
| SECONDARY Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24 |
-0.3; -3.2; -0.6; -4.6; -4.5 | <0.0001 sig |
| SECONDARY Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 |
7.7; 64.3; 7.6; 79.0; 82.5 | <0.0001 sig |
| SECONDARY Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 |
-0.160; -2.660; -0.730; -2.675; -2.665 | <0.0001 sig |
| SECONDARY NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 |
-0.320; -1.970; -0.640; -1.950; -1.930 | <0.0001 sig |
| SECONDARY Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 |
0.0; 21.4; 1.3; 27.2; 28.8 | 0.0017 sig |
| 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 |
-0.246; -0.614; -0.578; -0.593; -0.887 | 0.0077 sig |
| SECONDARY 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; -5.8; -4.0; -4.5; -5.4 | 0.0467 sig |
| SECONDARY Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24 |
-1.7; -3.4; -2.6; -3.0; -3.9 | 0.0051 sig |
| SECONDARY Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 |
12.8; 0.0; 2.5; 1.2; 2.5 | 0.0170 sig |
| SECONDARY Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24 |
— | — |
| 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 |
60.0; 55.9; 71.9; 67.6; 74.0; 84.6 | — |
| SECONDARY Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52 |
-21.71; -23.44; -23.69; -27.25; -20.87; -30.26 | — |
| SECONDARY Percent Change in DSQ Total Score at Week 52 |
-65.87; -75.93; -71.01; -78.13; -61.19; -80.74 | — |
| SECONDARY Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 |
-3.9; -4.1; -4.3; -6.1; -5.2; -5.3 | — |
| SECONDARY Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52 |
-83.76; -88.59; -91.20; -84.21; -84.78; -95.85 | — |
| SECONDARY Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52 |
-0.873; -0.873; -0.779; -0.906; -0.838; -0.968 | — |
| SECONDARY Absolute Change in EoEHSS Mean Stage Score at Week 52 |
-0.874; -0.891; -0.710; -0.871; -0.809; -0.932 | — |
| SECONDARY Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52 |
70.0; 82.4; 87.5; 78.4; 83.6; 100 | — |
| SECONDARY Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52 |
26.7; 29.4; 40.6; 16.2; 31.5; 30.8 | — |
| SECONDARY Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 |
-0.954; -0.911; -1.021; -0.858; -0.773; -0.935 | — |
| SECONDARY Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 |
-7.2; -5.9; -6.2; -5.9; -4.7; -6.4 | — |
| SECONDARY Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52 |
-4.3; -3.2; -4.0; -3.8; -3.6; -4.7 | — |
| SECONDARY Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period |
8.1; 0; 2.7; 2.7; 0; 1.4 | — |
| SECONDARY NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52 |
-2.580; -2.670; -2.28; -2.62; -2.64; -2.69 | — |
| SECONDARY NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52 |
-1.940; -1.970; -1.76; -1.96; -1.95; -1.97 | — |
| SECONDARY Concentration of Functional Dupilumab in Serum at Week 52 |
101; 205; 46.0; 124; 74.0; 195 | — |
| SECONDARY Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response |
0; 0; 0; 2; 1; 4 | — |
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
Eligibility 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 Exclusion Criteria (Part C):
- Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant
- Participants who became pregnant during Part A or Part B
- Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
- Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment
Note: Other inclusion/ exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT03633617). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.