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)
- Registration Number
- NCT06101095
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 64
- 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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab Dupilumab Subcutaneous injection (SC) as per protocol Placebo Placebo SC injection as per protocol
- Primary Outcome Measures
Name Time Method Change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe (EndoFLIP) 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 Outcome Measures
Name Time Method Change from baseline in EoE-HSS Stage From Baseline up to Week 128 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) At Weeks 24, 76 and 128 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 At Weeks 24, 76 and 128 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 From baseline up to Week 128 (EOT) 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 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) 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) 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 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 From baseline up to Week128 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) From baseline up to Week 128 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 From Baseline up to Week 128 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.
Trial Locations
- Locations (30)
Northwestern University Feinberg School of Medicine- Site Number : 8400003
🇺🇸Chicago, Illinois, United States
Private Practice - Dr. Martin Yudovich- Site Number : 8400015
🇺🇸Houston, Texas, United States
Itaigara Memorial - Hospital Dia- Site Number : 0760005
🇧🇷Salvador, Bahia, Brazil
Investigational Site Number : 1240006
🇨🇦Vancouver, British Columbia, Canada
United Gastroenterologists - Murrieta- Site Number : 8400001
🇺🇸Murrieta, California, United States
University of California San Francisco - Parnassus Heights- Site Number : 8400020
🇺🇸San Francisco, California, United States
Borland Groover Clinic- Site Number : 8400016
🇺🇸Jacksonville, Florida, United States
Treasure Valley Medical Research- Site Number : 8400018
🇺🇸Boise, Idaho, United States
GI Alliance - Glenview- Site Number : 8400012
🇺🇸Glenview, Illinois, United States
Illinois Gastroenterology Group- Site Number : 8400004
🇺🇸Gurnee, Illinois, United States
University of Iowa- Site Number : 8400006
🇺🇸Iowa City, Iowa, United States
University of Massachusetts Chan Medical School- Site Number : 8400019
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic Hospital Rochester- Site Number : 8400008
🇺🇸Rochester, Minnesota, United States
University of North Carolina at Chapel Hill- Site Number : 8400007
🇺🇸Chapel Hill, North Carolina, United States
Cleveland Clinic - Cleveland- Site Number : 8400009
🇺🇸Cleveland, Ohio, United States
Penn Medicine: University of Pennsylvania Health System- Site Number : 8400010
🇺🇸Philadelphia, Pennsylvania, United States
GI Alliance Research- Site Number : 8400017
🇺🇸Mansfield, Texas, United States
Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760006
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clínica Loema - Unidade I- Site Number : 0760007
🇧🇷Campinas, São Paulo, Brazil
Clinica de Alergia Martti Antila- Site Number : 0760001
🇧🇷Sorocaba, São Paulo, Brazil
Hospital Alemao Oswaldo Cruz - São Paulo- Site Number : 0760003
🇧🇷São Paulo, Brazil
Investigational Site Number : 1240004
🇨🇦Vancouver, British Columbia, Canada
Investigational Site Number : 1240002
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 3760006
🇮🇱Haifa, Israel
Investigational Site Number : 3760002
🇮🇱Haifa, Israel
Investigational Site Number : 3760005
🇮🇱Jerusalem, Israel
Investigational Site Number : 3760004
🇮🇱Jerusalem, Israel
Investigational Site Number : 3760003
🇮🇱Tel Aviv, Israel
Investigational Site Number : 7560001
🇨🇭Wetzikon, Switzerland
Investigational Site Number : 7560002
🇨🇭Zürich, Switzerland