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

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ClinicalTrials.gov Identifier: NCT04394351
Recruitment Status : Active, not recruiting
First Posted : May 19, 2020
Last Update Posted : November 15, 2021
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 7, 2020
First Posted Date  ICMJE May 19, 2020
Last Update Posted Date November 15, 2021
Actual Study Start Date  ICMJE September 1, 2020
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 15, 2021)
Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: Week 16 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 17, 2020)
Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: At week 16 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2021)
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: Week 16 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Week 16 ]
  • Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: Week 16 ]
    The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).
  • Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: Week 16 ]
    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.
  • Change in the type 2 inflammation transcriptional signature [ Time Frame: Week 16 ]
  • 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) [ Time Frame: Week 16 ]
    For patients aged ≥1 to <12 years 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.
  • Number of sign-free days during the 14-day period preceding week 16 as measured by the PESQ-C [ Time Frame: Week 16 ]
    For patients aged ≥1 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: Week 16 ]
    For patients aged ≥1 to <12 years
  • 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) [ Time Frame: Week 16 ]
    For patients aged ≥8 to <12 years 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.
  • Number of symptom-free days during the 14-day period preceding week 16 as measured by the PESQ-P (patient version) [ Time Frame: Week 16 ]
    For patients aged ≥8 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: Week 16 ]
    For patients aged ≥8 to <12 years
  • Change in total score as measured by the PEESSv2.0-caregiver version questionnaire [ Time Frame: Week 16 ]
    For patients aged ≥1 to <12 years 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
  • Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature [ Time Frame: Week 16 ]
    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.
  • NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Week 16 ]
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Week 16 ]
  • Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: Week 16 ]
  • Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: Week 16 ]
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Week 16 ]
  • Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer [ Time Frame: Week 16 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: Week 52 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: Week 52 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Week 52 ]
  • Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: Week 52 ]
  • Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: Week 52 ]
  • Change in the type 2 inflammation transcriptional signature [ Time Frame: Week 52 ]
  • Change in the proportion of days with 1 or more EoE signs as measured by the PESQ-C [ Time Frame: Week 52 ]
    For patients aged ≥1 to <12 years
  • Number of sign-free days during the 14-day period preceding week 52 as measured by the PESQ-C [ Time Frame: Week 52 ]
    For patients aged ≥1 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: Week 52 ]
    For patients aged ≥1 to <12 years
  • Change in the proportion of days with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: Week 52 ]
    For patients aged ≥8 to <12 years
  • Number of symptom-free days during the 14-day period preceding week 52 as measured by the PESQ-P (patient version) [ Time Frame: Week 52 ]
    For patients aged ≥8 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: Week 52 ]
    For patients aged ≥8 to <12 years
  • NES for the relative change in the EDP transcriptome signature [ Time Frame: Week 52 ]
  • NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Week 52 ]
  • Incidence of TEAEs [ Time Frame: Week 52 ]
  • Incidence of treatment-emergent SAEs [ Time Frame: Week 52 ]
  • Incidence of treatment-emergent AESIs [ Time Frame: Week 52 ]
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Week 52 ]
  • Incidence of treatment-emergent ADA responses and titer [ Time Frame: Week 52 ]
  • Concentration of functional dupilumab in serum [ Time Frame: Week 52 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2020)
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: At week 52 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: At week 16 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: At week 52 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 16 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 52 ]
  • Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: At week 16 ]
    The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).
  • Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: At week 52 ]
  • Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: At week 16 ]
    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.
  • Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: At week 52 ]
  • Change in the type 2 inflammation transcriptional signature [ Time Frame: At week 16 ]
  • Change in the type 2 inflammation transcriptional signature [ Time Frame: At week 52 ]
  • 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) [ Time Frame: At week 16 ]
    For patients aged ≥1 to <12 years 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.
  • Change in the proportion of days with 1 or more EoE signs as measured by the PESQ-C [ Time Frame: At week 52 ]
    For patients aged ≥1 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: At week 16 ]
    For patients aged ≥1 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: At week 52 ]
    For patients aged ≥1 to <12 years
  • 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) [ Time Frame: At week 16 ]
    For patients aged ≥8 to <12 years 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.
  • Change in the proportion of days with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 52 ]
    For patients aged ≥8 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 16 ]
    For patients aged ≥8 to <12 years
  • Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 52 ]
    For patients aged ≥8 to <12 years
  • Change in total score as measured by the PEESSv2.0-caregiver version questionnaire [ Time Frame: At week 16 ]
    For patients aged ≥1 to <12 years 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
  • Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature [ Time Frame: At week 16 ]
    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.
  • NES for the relative change in the EDP transcriptome signature [ Time Frame: At week 52 ]
  • NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 16 ]
  • NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 52 ]
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: At week 16 ]
  • Incidence of TEAEs [ Time Frame: At week 52 ]
  • Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: At week 16 ]
  • Incidence of treatment-emergent SAEs [ Time Frame: At week 52 ]
  • Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: At week 16 ]
  • Incidence of treatment-emergent AESIs [ Time Frame: At week 52 ]
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: At week 16 ]
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: At week 52 ]
  • Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer [ Time Frame: At week 16 ]
  • Incidence of treatment-emergent ADA responses and titer [ Time Frame: At week 52 ]
  • Concentration of functional dupilumab in serum [ Time Frame: Up to week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis
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 (52 weeks) dupilumab treatment
  • To assess safety, tolerability, and immunogenicity of long-term (52 weeks) dupilumab treatment
  • To evaluate the impact of dupilumab treatment on EoE signs and symptoms
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Eosinophilic Esophagitis (EoE)
Intervention  ICMJE
  • Drug: Dupilumab
    Single-use, prefilled glass syringe
    Other Names:
    • •DUPIXENT
    • •REGN668
    • •SAR231893
  • Drug: Matching Placebo
    Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: Dupilumab
    • Drug: Matching Placebo
  • Experimental: 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
    Interventions:
    • Drug: Dupilumab
    • Drug: Matching Placebo
  • Experimental: 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
    Interventions:
    • Drug: Dupilumab
    • Drug: Matching Placebo
  • Experimental: 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
    Interventions:
    • Drug: Dupilumab
    • Drug: Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 11, 2021)
90
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2020)
60
Estimated Study Completion Date  ICMJE July 31, 2023
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 11 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04394351
Other Study ID Numbers  ICMJE R668-EE-1877
2019-003078-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
URL: https://vivli.org/
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP