Clinical trial NCT06101095: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Eosinophilic Oesophagitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2023-10-25
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP)
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
timeFrame: From baseline up to Week 24
measure: Absolute change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
timeFrame: From baseline up to Week128
measure: Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe
timeFrame: From Baseline up to Week 128
measure: Change from baseline in eosinophilic esophagitis-endoscopic reference score (EoE-EREFS)
timeFrame: From baseline up to Week 128
measure: Change from baseline in eosinophilic esophagitis (EoE-HSS) Grade
timeFrame: From Baseline up to Week 128
measure: Change from baseline in EoE-HSS Stage
timeFrame: From Baseline up to Week 128
measure: Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤6 eosinophils/high power field (Eos/HPF)
timeFrame: At Weeks 24, 76 and 128
measure: Proportion of participants who achieved peak Esophageal Intraepithelial Eosinophil Count of ≤15 Eos/HPF
timeFrame: At Weeks 24, 76 and 128
measure: Change from baseline in normalized enrichment score (NES) for EoE diagnostic panel (EDP) transcriptome signature
timeFrame: From baseline up to Week 128 (EOT)
measure: Change from baseline in normalized enrichment score (NES) for type 2 inflammation transcriptome signature
timeFrame: From Baseline up to Week 128 (EOT)
measure: Incidence of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
timeFrame: From the first IMP administration up to end of post treatment follow up period (week139)
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: From the first IMP administration up to end of post treatment follow up period (week139)
Other outcomes:
Locations:
city: Murrieta
country: United States
facility: United Gastroenterologists - Murrieta- Site Number : 8400001
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Parnassus Heights- Site Number : 8400020
state: California
city: Jacksonville
country: United States
facility: Borland Groover Clinic- Site Number : 8400016
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research- Site Number : 8400018
state: Idaho
city: Chicago
country: United States
facility: Northwestern University- Site Number : 8400003
state: Illinois
city: Glenview
country: United States
facility: GI Alliance - Glenview- Site Number : 8400012
state: Illinois
city: Gurnee
country: United States
facility: Illinois Gastroenterology Group- Site Number : 8400004
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa- Site Number : 8400006
state: Iowa
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School- Site Number : 8400019
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Hospital Rochester- Site Number : 8400008
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill- Site Number : 8400007
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Cleveland- Site Number : 8400009
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System- Site Number : 8400010
state: Pennsylvania
city: Houston
country: United States
facility: Private Practice - Dr. Martin Yudovich- Site Number : 8400015
state: Texas
city: Mansfield
country: United States
facility: GI Alliance - Mansfield- Site Number : 8400017
state: Texas
city: Salvador
country: Brazil
facility: Itaigara Memorial - Hospital Dia- Site Number : 0760005
state: Bahia
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760006
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Clínica Loema - Unidade I- Site Number : 0760007
state: São Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila- Site Number : 0760001
state: São Paulo
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz - São Paulo- Site Number : 0760003
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240006
state: British Columbia
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240004
state: British Columbia
city: Montreal
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Haifa
country: Israel
facility: Investigational Site Number : 3760006
city: Haifa
country: Israel
facility: Investigational Site Number : 3760002
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760005
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760004
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760003
city: Wetzikon
country: Switzerland
facility: Investigational Site Number : 7560001
city: Zürich
country: Switzerland
facility: Investigational Site Number : 7560002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: