NCT04394351
Completed
Phase 3
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis
ConditionsEosinophilic Esophagitis (EoE)
Overview
- Phase
- Phase 3
- Intervention
- Dupilumab
- Conditions
- Eosinophilic Esophagitis (EoE)
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 102
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief 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
Detailed Description
This is a 3-part study: * Part A: Double-blind 16-week treatment period * Part B: 36-week extended active treatment period * Part C: Up to108 weeks open-label extension period
Investigators
Eligibility Criteria
Inclusion Criteria
- •A documented diagnosis of eosinophilic esophagitis (EoE)
- •Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
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):
Arms & Interventions
Part A - High Dose
Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Dupilumab
Part A - High Dose
Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Matching Placebo
Part A - Low Dose
Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Dupilumab
Part A - Low Dose
Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Matching Placebo
Part B - High Dose
Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Dupilumab
Part B - High Dose
Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Matching Placebo
Part B - Low Dose
Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Dupilumab
Part B - Low Dose
Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight
Intervention: Matching Placebo
Part C - High Dose
Part C consists of up to 108-week open-label extension period. All patients will receive higher exposure dupilumab subcutaneous (SC) administration at tiered dosing regimens based on body weight. No matching placebo administered in Part C.
Intervention: Dupilumab
Outcomes
Primary Outcomes
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
Time Frame: At Week 16
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Secondary Outcomes
- Part C: Number of Participants With Treatment-emergent SAEs(Up to Week 152)
- Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16(At Week 16)
- Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16(Baseline, Week 16)
- Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16(Baseline, Week 16)
- Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16(Baseline, Week 16)
- Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16(Baseline, Week 16)
- Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16(Baseline, Week 16)
- Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16(Baseline, Week 16)
- 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)(Baseline, Week 16)
- 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)(Week 16)
- 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(Baseline, Week 16)
- 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(Baseline, Week 16)
- 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)(Week 16)
- 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(Baseline, Week 16)
- 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(Baseline, Week 16)
- Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16(Baseline, Week 4 and 16)
- Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52(At Week 52)
- Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52(At Week 52)
- 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(Baseline up to Week 160)
- Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52(Baseline, Week 52)
- Part C: Number of Participants With Treatment-emergent ADA Responses(From Week 52 up to Week 152)
- Part C: Concentration of Functional Dupilumab in Serum at Week 100(At Week 100)
- Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52(Baseline, Week 52)
- Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52(Baseline, Week 52)
- 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(Baseline, Week 52)
- 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)(Week 52)
- 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(Baseline, Week 52)
- 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(Baseline, Week 52)
- 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)(Week 52)
- Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52(Baseline, Week 52)
- 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(Baseline, Week 52)
- Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52(Baseline, Week 52)
- Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52(Baseline, Week 52)
- Part B: Change From Baseline in Body Weight for Age Percentile at Week 52(Baseline, Week 52)
- Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52(Baseline, Week 52)
- Part B: Change From Baseline in Weight for Age Z-score at Week 52(Baseline, Week 52)
- Part B: Change From Baseline in Body Weight From Height Z-score at Week 52(Baseline, Week 52)
- Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52(Week 32 and 52)
- Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response(From Baseline up to Week 16 in Part A)
- Part C: Number of Participants With TEAEs(Up to Week 152)
- 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(From Baseline up to Week 16 in Part A)
- 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(From Week 16 up to Week 52 in Part B)
- Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category(From Baseline up to Week 16 in Part A)
- Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer(From Week 16 up to Week 52 in Part B)
- Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100(At Week 100)
- Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 160(At Week 160)
- Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100(Baseline to Week 100)
- Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 160(Baseline to Week 160)
- Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100(Baseline to Week 100)
- Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 160(Baseline to Week 160)
- Part C: Absolute Change in EoE-EREFS From Baseline to Week 100(Baseline to Week 100)
- Part C: Absolute Change in EoE-EREFS From Baseline to Week 160(Baseline to Week 160)
- Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100(Baseline to Week 100)
- Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100(Baseline to Week 100)
- Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 160(Baseline to Week 160)
- Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100(Baseline to Week 100)
- Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature From Baseline to Week 160(Baseline to Week 160)
- Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100(Baseline up to Week 100)
- Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100(Baseline up to Week 100)
- Part C: Change in Weight for Age Z-score From Baseline up to Week 100(Baseline up to Week 100)
- Part C: Change in Weight for Age Z-score From Baseline up to Week 160(Baseline up to Week 160)
- Part C: Change in Weight for Height Z-score From Baseline up to Week 100(Baseline up to Week 100)
- Part C: Change in Weight for Height Z-score From Baseline up to Week 160(Baseline up to Week 160)
- Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100(At Week 100)
- Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 160(At Week 160)
- 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(Baseline up to Week 100)
- Part C: Number of Participants With Treatment-emergent AESIs(Up to Week 152)
- Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment(Up to Week 152)
Study Sites (1)
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