Eosinophilic Oesophagitis
Conditions
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.
Interventions
DRUGDupilumab
Subcutaneous injection (SC) as per protocol
DRUGPlacebo
SC injection as per protocol
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| Percent change from baseline in esophageal distensibility plateau as measured by Functional Lumen Imaging Probe | From baseline up 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. |
| 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). |
| 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) | — |
| Incidence of adverse events of special interest (AESIs) | From the first IMP administration up to end of post treatment follow up period (week139) | — |
| 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). |
Countries
Brazil, Canada, Israel, Switzerland, United States
Outcome results
None listed