Phase 3
N=102
Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE)
Eosinophilic Esophagitis (EoE)
Bottom Line
View on ClinicalTrials.gov: NCT04394351 ↗Enrolled (actual)
102
Serious AEs
3.9%
Results posted
Aug 2024
Primary outcome: Primary: Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 — 2.9; 67.6; 58.1 percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dupilumab (Drug); Matching Placebo (Drug)
- Age
- Pediatric · 1+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 |
2.9; 67.6; 58.1 | <0.0001 sig |
| SECONDARY Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16 |
2.9; 83.8; 67.7 | <0.0001 sig |
| SECONDARY Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16 |
20.98; -86.09; -77.93 | <0.0001 sig |
| SECONDARY Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16 |
0.023; -0.879; -0.757 | <0.0001 sig |
| SECONDARY Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16 |
0.048; -0.835; -0.721 | <0.0001 sig |
| SECONDARY Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16 |
0.34; -1.895; -1.930 | <0.0001 sig |
| SECONDARY Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16 |
0.180; -2.630; -2.710 | <0.0001 sig |
| SECONDARY Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16 |
0.3; -3.5; -3.0 | <0.0001 sig |
| SECONDARY Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years) |
-0.17; -0.28; -0.18 | 0.1526 |
| SECONDARY Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) |
8.93; 10.38; 8.93 | 0.1507 |
| SECONDARY Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16 |
-0.11; -0.16; -0.09 | 0.2064 |
| SECONDARY Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16 |
-0.26; -0.13; -0.16 | 0.2086 |
| SECONDARY Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) |
10.49; 8.69; 9.13 | 0.2085 |
| SECONDARY Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16 |
-0.15; -0.08; -0.08 | 0.2360 |
| SECONDARY Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16 |
-11.83; -19.86; -10.10 | — |
| SECONDARY Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 |
0; 0; 75.7; 40.6; 163; 86.0 | — |
| SECONDARY Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 |
92.9; 52.9; 65.5; 62.9 | — |
| SECONDARY Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 |
92.9; 64.7; 69.0; 85.7 | — |
| SECONDARY Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 |
-92.72; -76.83; -85.41; -90.97 | — |
| SECONDARY Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 |
-0.804; -0.885; -0.773; -0.967 | — |
| SECONDARY Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 |
-0.767; -0.855; -0.784; -0.892 | — |
| SECONDARY Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 |
-5.82; -3.64; -4.50; -4.77 | — |
| SECONDARY Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 |
-0.20; -0.47; -0.49; -0.30 | — |
| SECONDARY Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) |
11.58; 12.10; 11.35; 12.13 | — |
| SECONDARY Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 |
-0.03; -0.24; -0.26; -0.17 | — |
| SECONDARY Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 |
-0.33; -0.43; -0.42; -0.26 | — |
| SECONDARY Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) |
9.33; 11.67; 10.64; 13.63 | — |
| SECONDARY Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 |
-0.17; -0.26; -0.21; -0.16 | — |
| SECONDARY Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 |
-2.715; -2.615; -2.625; -2.670 | — |
| SECONDARY Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 |
-1.960; -1.965; -1.920; -1.920 | — |
| SECONDARY Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 |
-0.02; 5.48; 4.75; 5.96 | — |
| SECONDARY Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 |
-0.0206; 0.0687; -0.0549; 0.0987 | — |
| SECONDARY Part B: Change From Baseline in Weight for Age Z-score at Week 52 |
0.0640; 0.2016; 0.1445; 0.2049 | — |
| SECONDARY Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 |
0.0962; -0.0100; -0.2700; -0.0151 | — |
| SECONDARY Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 |
105; 142; 99.0; 186; 101; 149 | — |
| SECONDARY Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug |
31; 27; 26; 0; 2; 1 | — |
| SECONDARY Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug |
14; 15; 28; 34; 1; 0 | — |
| SECONDARY Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response |
1; 1; 0 | — |
| SECONDARY Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category |
1; 1; 0; 0; 0; 0 | — |
| SECONDARY Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer |
0; 0; 0; 0 | — |
| SECONDARY Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100 |
92.7 | — |
| SECONDARY Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 160 |
— | — |
| SECONDARY Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100 |
-91.50 | — |
| SECONDARY Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 160 |
— | — |
| SECONDARY Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100 |
-0.851; -0.850 | — |
| SECONDARY Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 160 |
— | — |
| SECONDARY Part C: Absolute Change in EoE-EREFS From Baseline to Week 100 |
-5.34 | — |
| SECONDARY Part C: Absolute Change in EoE-EREFS From Baseline to Week 160 |
— | — |
| SECONDARY Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100 |
-25.03 | — |
| SECONDARY Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100 |
-2.720 | — |
| SECONDARY Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 160 |
— | — |
| SECONDARY Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100 |
-1.970 | — |
| SECONDARY Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature From Baseline to Week 160 |
— | — |
| SECONDARY Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100 |
10.63 | — |
| SECONDARY Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100 |
0.2009 | — |
| SECONDARY Part C: Change in Weight for Age Z-score From Baseline up to Week 100 |
0.3376 | — |
| SECONDARY Part C: Change in Weight for Age Z-score From Baseline up to Week 160 |
— | — |
| SECONDARY Part C: Change in Weight for Height Z-score From Baseline up to Week 100 |
0.3301 | — |
| SECONDARY Part C: Change in Weight for Height Z-score From Baseline up to Week 160 |
— | — |
| SECONDARY Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100 |
70.7 | — |
| SECONDARY Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 160 |
— | — |
| SECONDARY Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 100 |
14.8 | — |
| SECONDARY Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 160 |
— | — |
| SECONDARY Part C: Number of Participants With TEAEs |
53 | — |
| SECONDARY Part C: Number of Participants With Treatment-emergent SAEs |
3 | — |
| SECONDARY Part C: Number of Participants With Treatment-emergent AESIs |
6 | — |
| SECONDARY Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment |
— | — |
| SECONDARY Part C: Number of Participants With Treatment-emergent ADA Responses |
— | — |
| SECONDARY Part C: Concentration of Functional Dupilumab in Serum at Week 100 |
180 | — |
Summary
The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis (EoE) based on histologic improvement meeting validated histologic criteria.
The Secondary objectives are:
* To demonstrate the efficacy of dupilumab compared to placebo in pediatric patients with active EoE after 16 weeks of treatment as assessed by endoscopic visual measurements of disease activity using the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) and histologic abnormalities as measured by the EoE Histology Scoring System (EoE-HSS)
* To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 16 weeks in pediatric patients with active EoE
* To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
* To study the effects of dupilumab on the type 2 inflammation gene expression signature
* To evaluate the concentration-time profile of functional dupilumab in serum in this population
* To assess efficacy of long-term (up to 160 weeks) dupilumab treatment
* To assess the impact of dupilumab treatment on changes in weight and growth during the extended active period and open-label extension period of the study
* To assess safety, tolerability, and immunogenicity of long-term (up to 160 weeks) dupilumab treatment
* To evaluate the impact of dupilumab treatment on EoE signs and symptoms
Eligibility Criteria
Key Inclusion Criteria
- A documented diagnosis of eosinophilic esophagitis (EoE)
- Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
Key Exclusion Criteria
- Body weight <5 kg or ≥60 kg at screening
- Other causes of esophageal eosinophilia
- Active Helicobacter pylori
- History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery
- Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
- Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy
- History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure
- Active parasitic infection or suspected parasitic infection
- Known or suspected immunodeficiency disorder
Key Exclusion for Patients Re-Entering the Study (for Entry into Part C, as defined in protocol):
- Patients who are ≥12 years old, weigh ≥40 kg (or minimum weight for which dupilumab is approved for EoE), and dupilumab is commercially available for the treatment of EoE in their country
- Patients who, during their previous participation in this clinical trial, developed an SAE and/or AE deemed related to dupilumab, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient
- Patients who did not undergo endoscopy with biopsies at week 16 and/or week 52 or prior to receiving rescue treatment Note: If the endoscopy with biopsies could not occur due to COVID-19 restrictions and rescue treatment was needed to be initiated without delay, these patients will be eligible to participate in Part C
- Patients who became pregnant during their previous participation in this dupilumab clinical trial
- Patients who, during their previous participation in this trial, were prematurely withdrawn because of a protocol violation, poor compliance, or inability to complete required study assessments
NOTE: Other protocol defined inclusion/exclusion criteria apply
Data sourced from ClinicalTrials.gov (NCT04394351). 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.