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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis (EoE) Drug: Dupilumab Drug: Matching Placebo Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : August 8, 2022
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Dupilumab

Arm Intervention/treatment
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
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

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
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

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
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

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
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




Primary Outcome Measures :
  1. Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: Week 16 ]

Secondary Outcome Measures :
  1. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: Week 16 ]
  2. Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Week 16 ]
  3. 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).

  4. 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.

  5. Change in the type 2 inflammation transcriptional signature [ Time Frame: Week 16 ]
  6. 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.


  7. 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

  8. 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

  9. 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.


  10. 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

  11. 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

  12. 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


  13. 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.

  14. NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Week 16 ]
  15. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Week 16 ]
  16. Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: Week 16 ]
  17. Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: Week 16 ]
  18. Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Week 16 ]
  19. Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer [ Time Frame: Week 16 ]
  20. Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: Week 52 ]
  21. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: Week 52 ]
  22. Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Week 52 ]
  23. Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: Week 52 ]
  24. Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: Week 52 ]
  25. Change in the type 2 inflammation transcriptional signature [ Time Frame: Week 52 ]
  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. NES for the relative change in the EDP transcriptome signature [ Time Frame: Week 52 ]
  33. NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Week 52 ]
  34. Incidence of TEAEs [ Time Frame: Week 52 ]
  35. Incidence of treatment-emergent SAEs [ Time Frame: Week 52 ]
  36. Incidence of treatment-emergent AESIs [ Time Frame: Week 52 ]
  37. Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Week 52 ]
  38. Incidence of treatment-emergent ADA responses and titer [ Time Frame: Week 52 ]
  39. Concentration of functional dupilumab in serum [ Time Frame: Week 52 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

NOTE: Other protocol defined inclusion/exclusion criteria apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394351


Locations
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United States, Arizona
Regeneron Study Site
Phoenix, Arizona, United States, 85016
United States, Arkansas
Regeneron Study Site
Little Rock, Arkansas, United States, 72202
United States, California
Regeneron Study Site
Los Angeles, California, United States, 90027
Regeneron Study Site
San Francisco, California, United States, 94143
United States, Colorado
Regeneron Study Site
Aurora, Colorado, United States, 80045
United States, Florida
Regeneron Study Site
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Regeneron Study Site
Atlanta, Georgia, United States, 30322
Regeneron Study Site
Atlanta, Georgia, United States, 30342
United States, Illinois
Regeneron Study Site
Chicago, Illinois, United States, 60611
United States, Indiana
Regeneron Study Site
Indianapolis, Indiana, United States, 46202
United States, Iowa
Regeneron Study Site
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Regeneron Study Site
Boston, Massachusetts, United States, 02111
Regeneron Study Site
Boston, Massachusetts, United States, 02114
Regeneron Study Site
Boston, Massachusetts, United States, 02115
United States, Nebraska
Regeneron Study Site
Lincoln, Nebraska, United States, 68510
United States, New York
Regeneron Study Site
New York, New York, United States, 10029
Regeneron Study Site
New York, New York, United States, 10032
Regeneron Study Site
New York, New York, United States, 10065
United States, North Carolina
Regeneron Study Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Regeneron Study Site
Cincinnati, Ohio, United States, 45229
Regeneron Study Site
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Regeneron Study Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Regeneron Study Site
Dallas, Texas, United States, 75207
Regeneron Study Site
Fort Worth, Texas, United States, 76104
Regeneron Study Site
Houston, Texas, United States, 77030
United States, Wisconsin
Regeneron Study Site
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Regeneron Study Site
London, Ontario, Canada, N6A 5W9
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04394351    
Other Study ID Numbers: R668-EE-1877
2019-003078-24 ( EudraCT Number )
First Posted: May 19, 2020    Key Record Dates
Last Update Posted: November 15, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases