Study of Dupilumab in Adult Participants With Active Eosinophilic Esophagitis (EoE)

NCT02379052 | Completed Phase 2 Results FDA Drug

• 1 other identifier: R668-EE-1324
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 14

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

Conditions

Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10

  The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

  Baseline, Week 10

Secondary Outcomes (16)

• Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10

  Baseline, Week 10

• Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12

  Baseline, Week 12

• Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12

  Baseline, Week 12

• 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

  Baseline, Week 10

• 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

  Baseline, Week 12

Study Arms (2)

Dupilumab 300 mg QW

EXPERIMENTAL

Participants received SC dupilumab 300 mg during the 12-week double-blind treatment phase. Participants received 2 injections (300-mg initial dose, followed by a 300-mg loading dose) on day 1, followed by weekly injections.

Drug: Dupilumab

Placebo

EXPERIMENTAL

Participants received matching placebo once weekly (qw) during the 12-week double-blind treatment phase. Participants received 2 injections on day 1, followed by weekly injections.

Drug: Placebo

Interventions

Dupilumab DRUG

Also known as: DUPIXENT®, REGN668(SAR231893)

Dupilumab 300 mg QW

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of EoE by endoscopy prior to or at screening
• 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
• 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
• 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

You may not qualify if:

• Prior participation in a dupilumab (anti-IL-4R) clinical trial
• Other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis, and eosinophilic gastroenteritis
• History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery prior to screening
• 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
• History of bleeding disorders or esophageal varices
• 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
• Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening
• Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 3 months prior to screening
• 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
• Treatment with oral immunotherapy (OIT) within 6 months prior to screening
• Allergen immunotherapy unless on stable dose for at least 1 year prior to screening
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (14)

Unknown Facility

Idaho Falls, Idaho, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Urbana, Illinois, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Iowa City, Iowa, United States

Location

Unknown Facility

Chevy Chase, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Asheville, North Carolina, United States

Location

Unknown Facility

Chapel Hill, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Fairfax, Virginia, United States

Location

Related Publications (3)

• 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.

  PMID: 35636689 DERIVED

• 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.

  PMID: 34037993 DERIVED

• 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.

  PMID: 31593702 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: May 12, 2015
• Primary Completion: February 17, 2017
• Study Completion: July 10, 2017
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-02

Locations

US (14)