search
Back to results

A Study Assessing Esophageal Function and Remodeling With Dupilumab Compared With Placebo for 24 Weeks Followed by 104 Weeks Open Label in Adult Participants With EoE (REMOdeling With Dupilumab in Eosinophilic Esophagitis Long-term Trial)

Primary Purpose

Eosinophilic Oesophagitis

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Dupilumab
Placebo
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Eosinophilic Oesophagitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: A documented diagnosis of EoE by endoscopic biopsy. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration. History (by participant report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening. Body weight ≥40 kg. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome). Active Helicobacter pylori infection. History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening. History of bleeding disorders or esophageal varices. Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline. Initiation or change of a food elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to screening. Participation in prior dupilumab clinical study or participants currently treated or have been treated with commercially available dupilumab or contraindicated to dupilumab per local labelling. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Dupilumab

    Placebo

    Arm Description

    Subcutaneous injection (SC) as per protocol

    SC injection as per protocol

    Outcomes

    Primary Outcome Measures

    Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP)
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.

    Secondary Outcome Measures

    Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Absolute change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Change from baseline in eosinophilic esophagitis-endoscopic reference score (EoE-EREFS)
    EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease.
    Change from baseline in eosinophilic esophagitis (EoE-HSS) Grade
    Severity (grade) and extent (stage) of esophageal abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Higher score indicates greater severity and extent of histological abnormalities.
    Change from baseline in EoE-HSS Stage
    Severity (grade) and extent (stage) of esophageal abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Higher score indicates greater severity and extent of histological abnormalities.
    Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤6 eosinophils/high power field (Eos/HPF)
    Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
    Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤15 Eos/HPF
    Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
    Change from baseline in normalized enrichment score (NES) for EoE diagnostic panel (EDP) transcriptome signature
    NES reflects the degree to which the activity level of a set of disease 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. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
    Change from baseline in normalized enrichment score (NES) for type 2 inflammation transcriptome signature
    NES reflects the degree to which the activity level of a set of disease 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. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
    Incidence of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
    Incidence of adverse events of special interest (AESIs)

    Full Information

    First Posted
    October 19, 2023
    Last Updated
    October 19, 2023
    Sponsor
    Sanofi
    Collaborators
    Regeneron Pharmaceuticals
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT06101095
    Brief Title
    A Study Assessing Esophageal Function and Remodeling With Dupilumab Compared With Placebo for 24 Weeks Followed by 104 Weeks Open Label in Adult Participants With EoE (REMOdeling With Dupilumab in Eosinophilic Esophagitis Long-term Trial)
    Official Title
    A Phase 4, Randomized, Multicenter, Double-blind, Parallel-group, 24 Weeks, Placebo-controlled Study Followed by 104 Weeks Open-label to Assess Dupilumab Efficacy on Esophageal Function and Remodeling in Adult Participants With Eosinophilic Esophagitis (EoE)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 20, 2023 (Anticipated)
    Primary Completion Date
    July 28, 2025 (Anticipated)
    Study Completion Date
    November 11, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Sanofi
    Collaborators
    Regeneron Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is parallel, Phase 4 study which consists of a 24 week (0.5 years) randomized, double blind, placebo controlled, 2-arm treatment period followed by an open label segment of 104 weeks (2 years) for a total of 128 weeks (2.5 years) to evaluate the effect of dupilumab treatment on esophageal function, and remodeling in adults with eosinophilic esophagitis. Duration of study period (per participant) Screening period: Up to 12 weeks before Week 0 Randomized double-blind period: 24 weeks Open label period: 104 weeks Post Investigational Medicinal Product (IMP) intervention follow-up period: up to 12 weeks or until the participants switch to commercialized dupilumab, whatever comes first. There will be ten (10) site visits, and five (5) direct-to-participant IMP delivery visits (except if prohibited by local regulatory authorities or if participant is not willing. In this case, IMP will be dispensed at the study site).
    Detailed Description
    The duration per participant will be up to 152 weeks.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Eosinophilic Oesophagitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    64 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Dupilumab
    Arm Type
    Experimental
    Arm Description
    Subcutaneous injection (SC) as per protocol
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    SC injection as per protocol
    Intervention Type
    Drug
    Intervention Name(s)
    Dupilumab
    Intervention Description
    Subcutaneous injection (SC) as per protocol
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    SC injection as per protocol
    Primary Outcome Measure Information:
    Title
    Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP)
    Description
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Time Frame
    From baseline to Week 24
    Secondary Outcome Measure Information:
    Title
    Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Description
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Time Frame
    From baseline up to Week 24
    Title
    Absolute change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Description
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Time Frame
    From baseline up to Week128
    Title
    Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
    Description
    Distensibility plateau provides an assessment of esophageal function. An increase in distensibility plateau indicates an improvement in esophageal function and a decrease in distensibility plateau indicates a worsening of esophageal function.
    Time Frame
    From Baseline up to Week 128
    Title
    Change from baseline in eosinophilic esophagitis-endoscopic reference score (EoE-EREFS)
    Description
    EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease.
    Time Frame
    From baseline up to Week 128
    Title
    Change from baseline in eosinophilic esophagitis (EoE-HSS) Grade
    Description
    Severity (grade) and extent (stage) of esophageal abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Higher score indicates greater severity and extent of histological abnormalities.
    Time Frame
    From Baseline up to Week 128
    Title
    Change from baseline in EoE-HSS Stage
    Description
    Severity (grade) and extent (stage) of esophageal abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Higher score indicates greater severity and extent of histological abnormalities.
    Time Frame
    From Baseline up to Week 128
    Title
    Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤6 eosinophils/high power field (Eos/HPF)
    Description
    Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
    Time Frame
    At Weeks 24, 76 and 128
    Title
    Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤15 Eos/HPF
    Description
    Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
    Time Frame
    At Weeks 24, 76 and 128
    Title
    Change from baseline in normalized enrichment score (NES) for EoE diagnostic panel (EDP) transcriptome signature
    Description
    NES reflects the degree to which the activity level of a set of disease 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. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
    Time Frame
    From baseline up to Week 128 (EOT)
    Title
    Change from baseline in normalized enrichment score (NES) for type 2 inflammation transcriptome signature
    Description
    NES reflects the degree to which the activity level of a set of disease 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. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
    Time Frame
    From Baseline up to Week 128 (EOT)
    Title
    Incidence of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
    Time Frame
    From the first IMP administration up to end of post treatment follow up period (week139)
    Title
    Incidence of adverse events of special interest (AESIs)
    Time Frame
    From the first IMP administration up to end of post treatment follow up period (week139)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: A documented diagnosis of EoE by endoscopic biopsy. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration. History (by participant report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening. Body weight ≥40 kg. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome). Active Helicobacter pylori infection. History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening. History of bleeding disorders or esophageal varices. Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline. Initiation or change of a food elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to screening. Participation in prior dupilumab clinical study or participants currently treated or have been treated with commercially available dupilumab or contraindicated to dupilumab per local labelling. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Trial Transparency email recommended (Toll free for US & Canada)
    Phone
    800-633-1610
    Ext
    option 6
    Email
    Contact-US@sanofi.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Sciences & Operations
    Organizational Affiliation
    Sanofi
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

    Learn more about this trial

    A Study Assessing Esophageal Function and Remodeling With Dupilumab Compared With Placebo for 24 Weeks Followed by 104 Weeks Open Label in Adult Participants With EoE (REMOdeling With Dupilumab in Eosinophilic Esophagitis Long-term Trial)

    We'll reach out to this number within 24 hrs