Clinical trial NCT03633617: Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
Official title: A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Esophagitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-08-16
Enrollment: 321
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study by study part are:

Part A:

To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B.

Part B:

To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures.

Part C:

To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.

The secondary objectives of the study are:

* To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE
* To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses
* To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
* To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids


Eligibility criteria: Key Inclusion Criteria (Parts A \& B):

* A documented diagnosis of EoE by endoscopic biopsy
* Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
* History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening

Key Exclusion Criteria (Parts A \& B):

* Body weight ≤40 kg
* Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
* Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening.
* Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and 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
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Key Exclusion Criteria (Part C):

* Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant
* Participants who became pregnant during Part A or Part B
* Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
* Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment

Note: Other inclusion/ exclusion criteria apply

Primary outcomes:
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) in All Three Regions at Week 24
timeFrame: At week 24
measure: Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24
timeFrame: Baseline and week 24
measure: Percent Change From Baseline in DSQ Total Score at Week 24
timeFrame: Baseline and week 24
measure: Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24
timeFrame: Baseline and week 24
measure: Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24
timeFrame: Baseline and week 24
measure: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24
timeFrame: At week 24
measure: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24
timeFrame: Baseline and week 24
measure: NES for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24
timeFrame: At week 24
measure: Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by EoE Impact Questionnaire (EoE-IQ) at Week 24
timeFrame: Baseline and week 24
measure: Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24
timeFrame: Baseline and week 24
measure: Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 24
timeFrame: Baseline and week 24
measure: Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24
timeFrame: At week 24
measure: Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24
timeFrame: At week 24
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) in All Three Regions at Week 52
timeFrame: At week 52
measure: Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Percent Change in DSQ Total Score at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Absolute Change in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Absolute Change in EoE Histology Scoring System (EoEHSS) Mean Grade Score at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Absolute Change in EoEHSS Mean Stage Score at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 52
timeFrame: At week 52
measure: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 52
timeFrame: At week 52
measure: Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE-SQ at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Percentage of Participants Who Received Rescue Medication During the 28-week Extended Active Treatment Period
timeFrame: Baseline (of Part C) to week 28
measure: NES for the Relative Change From Baseline in EoE Diagnostic Panel (EDP) at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: NES for the Relative Change in the Type 2 Inflammation Signature (T2INF) at Week 52
timeFrame: Baseline (of previous study part) and week 52
measure: Concentration of Functional Dupilumab in Serum at Week 52
timeFrame: Baseline (of Part C) up to week 52
measure: Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response
timeFrame: Baseline (of previous study part) up to week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Regeneron Study Site
state: Arizona
city: Scottsdale
country: United States
facility: Regeneron Study Site
state: Arizona
city: Little Rock
country: United States
facility: Regeneron Study Site
state: Arkansas
city: La Jolla
country: United States
facility: Regeneron Study Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Study Site
state: California
city: Mountain View
country: United States
facility: Regeneron Study Site
state: California
city: Orange
country: United States
facility: Regeneron Study Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Study Site
state: California
city: San Diego
country: United States
facility: Regeneron Study Site
state: California
city: Aurora
country: United States
facility: Regeneron Study Site
state: Colorado
city: Aurora
country: United States
facility: Regeneron Study Site
state: Colorado
city: Colorado Springs
country: United States
facility: Regeneron Study Site
state: Colorado
city: Lone Tree
country: United States
facility: Regeneron Study Site
state: Colorado
city: Bristol
country: United States
facility: Regeneron Study Site
state: Connecticut
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Saint Petersburg
country: United States
facility: Regeneron Study Site
state: Florida
city: Boise
country: United States
facility: Regeneron Study Site
state: Idaho
city: Idaho Falls
country: United States
facility: Regeneron Study Site
state: Idaho
city: Chicago
country: United States
facility: Regeneron Study Site #1
state: Illinois
city: Chicago
country: United States
facility: Regeneron Study Site #2
state: Illinois
city: Park Ridge
country: United States
facility: Regeneron Study Site
state: Illinois
city: Urbana
country: United States
facility: Regeneron Study Site
state: Illinois
city: Indianapolis
country: United States
facility: Regeneron Study Site
state: Indiana
city: Clive
country: United States
facility: Regeneron Study Site
state: Iowa
city: Iowa City
country: United States
facility: Regeneron Study Site
state: Iowa
city: Topeka
country: United States
facility: Regeneron Study Site
state: Kansas
city: Hagerstown
country: United States
facility: Regeneron Study Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Worcester
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Regeneron Study Site
state: Michigan
city: Chesterfield
country: United States
facility: Regeneron Study Site
state: Michigan
city: Plymouth
country: United States
facility: Regeneron Study Site
state: Minnesota
city: Rochester
country: United States
facility: Regeneron Study Site
state: Minnesota
city: Lincoln
country: United States
facility: Regeneron Study Site
state: Nebraska
city: Omaha
country: United States
facility: Regeneron Study Site
state: Nebraska
city: Bronx
country: United States
facility: Regeneron Study Site
state: New York
city: Great Neck
country: United States
facility: Regeneron Study Site
state: New York
city: Great Neck
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: New York
country: United States
facility: Regeneron Study Site
state: New York
city: Chapel Hill
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Cincinnati
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dayton
country: United States
facility: Regeneron Study Site
state: Ohio
city: Dublin
country: United States
facility: Regeneron Study Site
state: Ohio
city: Mentor
country: United States
facility: Regeneron Study Site
state: Ohio
city: Hershey
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Charleston
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Greenville
country: United States
facility: Regeneron Study Site
state: South Carolina
city: Johnson City
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Memphis
country: United States
facility: Regeneron Study Site
state: Tennessee
city: Dallas
country: United States
facility: Regeneron Study Site
state: Texas
city: Fort Worth
country: United States
facility: Regeneron Study Site
state: Texas
city: Garland
country: United States
facility: Regeneron Study Site
state: Texas
city: Houston
country: United States
facility: Regeneron Study Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Study Site
state: Texas
city: Salt Lake City
country: United States
facility: Regeneron Study Site
state: Utah
city: Charlottesville
country: United States
facility: Regeneron Study Site
state: Virginia
city: Roanoke
country: United States
facility: Regeneron Study Site
state: Virginia
city: Seattle
country: United States
facility: Regeneron Study Site
state: Washington
city: Milwaukee
country: United States
facility: Regeneron Study Site
state: Wisconsin
city: Camperdown
country: Australia
facility: Regeneron Study Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Regeneron Study Site
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Regeneron Study Site
state: South Australia
city: Melbourne
country: Australia
facility: Regeneron Study Site
state: Victoria
city: Bruges
country: Belgium
facility: Regeneron Study Site
city: Edegem
country: Belgium
facility: Regeneron Study Site
city: Leuven
country: Belgium
facility: Regeneron Study Site
city: London
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Ottawa
country: Canada
facility: Regeneron Study Site
state: Ontario
city: Montreal
country: Canada
facility: Regeneron Study Site
state: Quebec
city: Hamilton
country: Canada
facility: Regeneron Study Site
city: Pessac
country: France
facility: Regeneron Study Site
city: Toulouse
country: France
facility: Regeneron Study Site
city: Hannover
country: Germany
facility: Regeneron Study Site
city: Magdeburg
country: Germany
facility: Regeneron Study Site
city: Munich
country: Germany
facility: Regeneron Study Site
city: Genoa
country: Italy
facility: Regeneron Study Site
city: Milano
country: Italy
facility: Regeneron Study Site
city: Naples
country: Italy
facility: Regeneron Study Site
city: Pisa
country: Italy
facility: Regeneron Study Site
city: Rome
country: Italy
facility: Regeneron Study Site
city: Rome
country: Italy
facility: Regeneron Study Site
city: Rozzano
country: Italy
facility: Regeneron Study Site
city: Amsterdam
country: Netherlands
facility: Regeneron Study Site
city: Maastricht
country: Netherlands
facility: Regeneron Study Site
city: Nijmegen
country: Netherlands
facility: Regeneron Study Site
city: Tomelloso
country: Spain
facility: Regeneron Study Site
state: Ciudad Real
city: Barcelona
country: Spain
facility: Regeneron Study Site
city: Madrid
country: Spain
facility: Regeneron Study Site
city: Stockholm
country: Sweden
facility: Regeneron Study Site
city: Zurich
country: Switzerland
facility: Regeneron Study Site
city: London
country: United Kingdom
facility: Regeneron Study Site
state: Whitechapel
city: Barnsley
country: United Kingdom
facility: Regeneron Study Site
state: Yorkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: