Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE)

Eosinophilic Esophagitis (EoE) Clinical Trial

— EoE KIDS  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04394351
• Other study ID #: R668-EE-1877
• Secondary ID: 2019-003078-24
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 1, 2020
• Est. completion date: July 7, 2025

Study information

• Verified date: June 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: July 7, 2025
• Est. primary completion date: June 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 11 Years

Eligibility

Key Inclusion Criteria:

1. A documented diagnosis of eosinophilic esophagitis (EoE)

2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration

Key Exclusion Criteria:

1. Body weight <5 kg or =60 kg at screening

2. Other causes of esophageal eosinophilia

3. Active Helicobacter pylori

4. History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery

5. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening

6. Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy

7. 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

8. Active parasitic infection or suspected parasitic infection

9. Known or suspected immunodeficiency disorder

Key Exclusion for Patients Re-Entering the Study (for Entry into Part C, as defined in protocol):

1. 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

2. 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

3. 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

4. Patients who became pregnant during their previous participation in this dupilumab clinical trial

5. 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

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Eosinophilic Esophagitis (EoE)
• Esophagitis

Intervention

Drug:
• Dupilumab
Single-use, prefilled syringe
• Matching Placebo
Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance

Locations

Country	Name	City	State
Canada	Regeneron Study Site	London	Ontario
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Aurora	Colorado
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Chapel Hill	North Carolina
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Cincinnati	Ohio
United States	Regeneron Study Site	Cleveland	Ohio
United States	Regeneron Study Site	Dallas	Texas
United States	Regeneron Study Site	Fort Worth	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Indianapolis	Indiana
United States	Regeneron Study Site	Iowa City	Iowa
United States	Regeneron Study Site	Lincoln	Nebraska
United States	Regeneron Study Site	Little Rock	Arkansas
United States	Regeneron Study Site	Los Angeles	California
United States	Regeneron Study Site	Milwaukee	Wisconsin
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Philadelphia	Pennsylvania
United States	Regeneron Study Site	Phoenix	Arizona
United States	Regeneron Study Site	Saint Petersburg	Florida
United States	Regeneron Study Site	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count =6 eos/hpf (400×)		At Week 16
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part A	At Week 16
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part B	At Week 52
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part C	At Week 100
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part C	At Week 160
Secondary	Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part A	Baseline to Week 16
Secondary	Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part B	Baseline to Week 52
Secondary	Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part C	Baseline to Week 100
Secondary	Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part C	Baseline to Week 160
Secondary	Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS)	Part A; The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).	Baseline to Week 16
Secondary	Absolute change in mean EoE-HSS	Part B; The EoEHSS as stated above.	Baseline to Week 52
Secondary	Absolute change in mean EoE-HSS	Part C; The EoEHSS as stated above.	Baseline to Week 100
Secondary	Absolute change in mean EoE-HSS	Part C; The EoEHSS as stated above.	Baseline to Week 160
Secondary	Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS)	Part A; EoE esophageal characteristics will be analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease using both overall scores and scores for each individual characteristic. The proximal and distal esophageal regions will be scored separately; The score for each region ranges from 0 to 9 and the overall score ranges from 0 to 18.	Baseline to Week 16
Secondary	Absolute change in EoE-EREFS	Part B; EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 52
Secondary	Absolute change in EoE-EREFS	Part C; EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 100
Secondary	Absolute change in EoE-EREFS	Part C; EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 160
Secondary	Change in the type 2 inflammation transcriptional signature	Part A	Baseline at Week 16
Secondary	Change in the type 2 inflammation transcriptional signature	Part B	Baseline at Week 52
Secondary	Change in the proportion of days with 1 or more EoE signs as measured by the Pediatric EoE Sign/Symptom Questionnaire- Caregiver version (PESQ-C)	Part A: For patients aged =1 to <12 years; The PESQ-C is an observer-reported outcome measure intended to be completed independently by caregivers. The PESQ-C will measure occurrence of signs of EoE and will be completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding the week 16 visit will be used to calculate the proportion of days or total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE signs.	Baseline to Week 16
Secondary	Change in the proportion of days with 1 or more EoE signs as measured by the PESQ-C	Part B: For patients aged =1 to <12 years; The PESQ-C as stated above.	Baseline to Week 52
Secondary	Number of sign-free days during the 14-day period preceding week 16 as measured by the PESQ-C	Part A: For patients aged =1 to <12 years; The PESQ-C as stated above.	Up to Week 16
Secondary	Number of sign-free days during the 14-day period preceding week 52 as measured by the PESQ-C	Part B: For patients aged =1 to <12 years; The PESQ-C as stated above.	Up to Week 52
Secondary	Change in the proportion of total segments within a day with 1 or more EoE signs as measured by the PESQ-C	Part A: For patients aged =1 to <12 years; The PESQ-C as stated above.	Baseline to Week 16
Secondary	Change in the proportion of total segments within a day with 1 or more EoE signs as measured by the PESQ-C	Part B: For patients aged =1 to <12 years; The PESQ-C as stated above.	Baseline to Week 52
Secondary	Change in the proportion of days with 1 or more EoE symptoms as measured by the Pediatric EoE Sign/Symptom Questionnaire- Patient version (PESQ-P)	Part A: For patients aged =8 to <12 years; The PESQ-P is a patient-reported outcome measure intended to be completed independently by EoE patients. The PESQ-P will measure occurrence and severity of EoE symptoms and will be completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding the week 16 visit will be used to calculate the proportion of days or total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.	Baseline to Week 16
Secondary	Change in the proportion of days with 1 or more EoE symptoms as measured by the PESQ-P	Part B: For patients aged =8 to <12 years; The PESQ-P as stated above.	Baseline to Week 52
Secondary	Number of symptom-free days during the 14-day period preceding week 16 as measured by the PESQ-P	Part A: For patients aged =8 to <12 years; The PESQ-P as stated above.	Up to Week 16
Secondary	Number of symptom-free days during the 14-day period preceding week 52 as measured by the PESQ-P	Part B: For patients aged =8 to <12 years; The PESQ-P as stated above.	Up to Week 52
Secondary	Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by the PESQ-P	Part A: For patients aged =8 to <12 years; The PESQ-P as stated above.	Baseline to Week 16
Secondary	Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by the PESQ-P	Part B: For patients aged =8 to <12 years; The PESQ-P as stated above.	Baseline to Week 52
Secondary	Change in total score as measured by the PEESSv2.0-caregiver version questionnaire	Part A: For patients aged =1 to <12 years; The PEESSv2.0-caregiver version assesses the frequency and severity of EoE symptoms among pediatric patients (Franciosi, 2011). The PEESSv2.0 consists of 20 items and has a one-month recall period. The total score ranges from 0 to 100; higher scores indicate greater symptom burden of among pediatric EoE patients	Baseline to Week 16
Secondary	Change in total score as measured by the PEESSv2.0- caregiver version questionnaire	Part C; The PEESSv2.0-caregiver version as stated above.	Baseline to Week 160
Secondary	Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature	Part A; NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set (Barbie, 2009)(Subramanian, 2005). NES scores will be calculated for each transcriptome signature for each sample for statistical analyses.	Baseline to Week 16
Secondary	NES for the relative change in the EDP transcriptome signature	Part B; NES as stated above.	Baseline to Week 52
Secondary	NES for the relative change in the EDP transcriptome signature	Part C; NES as stated above.	Baseline to Week 100
Secondary	NES for the relative change in the EDP transcriptome signature	Part C; NES as stated above.	Baseline to Week 160
Secondary	NES for the relative change in the type 2 inflammation transcriptome signature	Part A; NES as stated above.	Baseline to Week 16
Secondary	NES for the relative change in the type 2 inflammation transcriptome signature	Part B; NES as stated above.	Baseline to Week 52
Secondary	NES for the relative change in the type 2 inflammation transcriptome signature	Part C; NES as stated above.	Baseline to Week 100
Secondary	Change in body weight for age percentile	Part B	Baseline at Week 52
Secondary	Change in body weight for age percentile	Part C	Baseline up to Week 160
Secondary	Change in body mass index for age z-score	Part B: For patients =2 years of age	Baseline to Week 52
Secondary	Change in body mass index for age z-score	Part C: For patients =2 years of age	Baseline to up to Week 160
Secondary	Change in weight for age z-score	Part B	Baseline to Week 52
Secondary	Change in weight for age z-score	Part C	Baseline up to Week 160
Secondary	Change in weight for height z-score	Part B	Baseline to Week 52
Secondary	Change in weight for height z-score	Part C	Baseline up to Week 160
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of =6 eos/hpf (400×)	Part C	At Week 100
Secondary	Proportion of patients achieving peak esophageal intraepithelial eosinophil count of =6 eos/hpf (400×)	Part C	At Week 160
Secondary	Proportion of patients (with food elimination diet regimens at baseline) that have a re-introduction of a previously eliminated food group	Part C	Baseline by Week 100
Secondary	Proportion of patients (with food elimination diet regimens at baseline) that have a re-introduction of a previously eliminated food group	Part C	Baseline by Week 160
Secondary	Incidence of treatment-emergent adverse events (TEAEs)	Part A	Up to Week 16
Secondary	Incidence of TEAEs	Part B	Up to Week 52
Secondary	Incidence of TEAEs	Part C	Up to Week 160
Secondary	Incidence of treatment-emergent serious adverse events (SAEs)	Part A	Up to Week 16
Secondary	Incidence of treatment-emergent SAEs	Part B	Up to Week 52
Secondary	Incidence of treatment-emergent SAEs	Part C	Up to Week 160
Secondary	Incidence of treatment-emergent adverse events of special interest (AESIs)	Part A	Up to Week 16
Secondary	Incidence of treatment-emergent AESIs	Part B	Up to Week 52
Secondary	Incidence of treatment-emergent AESIs	Part C	Up to Week 160
Secondary	Incidence of TEAEs leading to permanent discontinuation of study treatment	Part A	Up to Week 16
Secondary	Incidence of TEAEs leading to permanent discontinuation of study treatment	Part B	Up to Week 52
Secondary	Incidence of TEAEs leading to permanent discontinuation of study treatment	Part C	Up to Week 160
Secondary	Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer	Part A	Up to Week 16
Secondary	Incidence of treatment-emergent ADA responses and titer	Part B	Up to Week 52
Secondary	Incidence of treatment-emergent ADA responses and titer	Part C	Up to Week 160
Secondary	Concentration of functional dupilumab in serum		Baseline to end of study, Up to Week 160