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)

Sanofi30 sites in 5 countries69 target enrollmentNovember 29, 2023

ConditionsEosinophilic Oesophagitis

InterventionsDupilumab Placebo

DrugsDupilumab Placebo

Overview

Phase: Phase 4
Intervention: Dupilumab
Conditions: Eosinophilic Oesophagitis
Sponsor: Sanofi
Enrollment: 69
Locations: 30
Primary Endpoint: Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP)
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 29, 2023

End Date

February 1, 2028

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

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

Arms & Interventions

Dupilumab

Subcutaneous injection (SC) as per protocol

Intervention: Dupilumab

Placebo

SC injection as per protocol

Intervention: Placebo

Outcomes

Primary Outcomes

Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP)

Time Frame: From baseline to Week 24

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 Outcomes

Change from baseline in EoE-HSS Stage(From Baseline up to Week 128)
Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤6 eosinophils/high power field (Eos/HPF)(At Weeks 24, 76 and 128)
Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤15 Eos/HPF(At Weeks 24, 76 and 128)
Change from baseline in normalized enrichment score (NES) for EoE diagnostic panel (EDP) transcriptome signature(From baseline up to Week 128 (EOT))
Incidence of adverse events of special interest (AESIs)(From the first IMP administration up to end of post treatment follow up period (week139))
Change from baseline in normalized enrichment score (NES) for type 2 inflammation transcriptome signature(From Baseline up to Week 128 (EOT))
Incidence of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)(From the first IMP administration up to end of post treatment follow up period (week139))
Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe(From Baseline up to Week 128)
Absolute change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe(From baseline up to Week128)
Change from baseline in eosinophilic esophagitis-endoscopic reference score (EoE-EREFS)(From baseline up to Week 128)
Change from baseline in eosinophilic esophagitis (EoE-HSS) Grade(From Baseline up to Week 128)