Clinical trial NCT02379052: Study of Dupilumab in Adult Participants With Active Eosinophilic Esophagitis (EoE)
Official title: A Randomized, Double-Blind, Parallel, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Dupilumab in Adult Patients With Active Eosinophilic Esophagitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Esophagitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2015-03-04
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess the clinical efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, to relieve symptoms in adult participants with active, moderate to severe Eosinophilic Esophagitis (EoE).

The secondary objectives of the study are:

* To assess the safety, tolerability, and immunogenicity of SC doses of dupilumab in adult participants with active, moderate to severe EoE
* To assess the effect of dupilumab on esophageal eosinophilic infiltration
* To evaluate the pharmacokinetics (PK) of dupilumab in adult participants with EoE


Eligibility criteria: Key inclusion criteria:

1. Documented diagnosis of EoE by endoscopy prior to or at screening
2. History of on average at least 2 episodes of dysphagia (with intake of solids off anti-inflammatory therapy) per week in the 4 weeks prior to screening and on average at least 2 episodes of documented dysphagia per week in the weeks between screening and baseline; dysphagia is defined as trouble swallowing solid food, or having solid food stick, by participant report
3. Must remain on a stabilized diet for at least 6 weeks prior to screening and during the course of the study; stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups
4. Documented history of or presence of any of the following: allergic disease (e.g, allergic asthma, allergic rhinitis, atopic dermatitis (AD), or food allergies), peripheral eosinophil counts ≥0.25 GI/L, or serum total Immunoglobulin E (IgE) ≥100 kU/L

Key Exclusion Criteria:

1. Prior participation in a dupilumab (anti-IL-4R) clinical trial
2. Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis
3. History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery prior to screening
4. Any esophageal stricture unable to be passed with a standard, diagnostic, adult (9 to10 mm) upper endoscope or any critical esophageal stricture that requires dilation at screening
5. History of bleeding disorders or esophageal varices
6. Use of chronic aspirin, nonsteroidal agents, or anti-coagulants within 2 weeks prior to screening. Participants should not stop these agents solely to become eligible for entry into this study
7. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening
8. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 3 months prior to screening
9. Use of inhaled (pulmonary or nasal) topical corticosteroids within 3 months prior to screening and during the study, except stable dose for at least 3 months prior to screening biopsy, which cannot be changed during the study
10. Treatment with oral immunotherapy (OIT) within 6 months prior to screening
11. Allergen immunotherapy unless on stable dose for at least 1 year prior to screening
12. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Note: The list of inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial.

Primary outcomes:
measure: Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
timeFrame: Baseline, Week 10
Secondary outcomes:
measure: Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10
timeFrame: Baseline, Week 10
measure: Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10
timeFrame: Baseline, Week 10
measure: Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10
timeFrame: Baseline, Week 10
measure: Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10
timeFrame: Baseline, Week 10
measure: Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10
timeFrame: Baseline, Week 10
measure: Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophils of 3 Esophageal Regions at Week 12
timeFrame: Baseline, Week 12
measure: Absolute Change From Baseline in Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) by Feature at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QOL-A) Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Use of Rescue Medication or Procedure (e.g., Esophageal Dilation) Through Week 12
timeFrame: Baseline through Week 12
measure: Percent of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Study
timeFrame: Baseline through Week 28
Other outcomes:
Locations:
city: Idaho Falls
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Urbana
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Chevy Chase
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Fairfax
country: United States
state: Virginia
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.
citation: Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amin N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pirozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.
citation: Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, Schoepfer AM, Safroneeva E, Rothenberg ME, Falk GW, Assouline-Dayan Y, Zhao Q, Chen Z, Swanson BN, Pirozzi G, Mannent L, Graham NMH, Akinlade B, Stahl N, Yancopoulos GD, Radin A. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2020 Jan;158(1):111-122.e10. doi: 10.1053/j.gastro.2019.09.042. Epub 2019 Oct 5.