Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)

NCT03633617 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: R668-EE-17742018-000844-25
• Study Type: interventional
• Target: 321
• Locations: 12 countries
• Sites: 95

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

Conditions

Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (2)

• 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

  Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).

  At week 24

• Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24

  The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.

  Baseline and week 24

Secondary Outcomes (31)

• Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) in All Three Regions at Week 24

  Baseline and week 24

• Percent Change From Baseline in DSQ Total Score at Week 24

  Baseline and week 24

• Absolute Change From Baseline in Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Mean Grade Score at Week 24

  Baseline and week 24

• Absolute Change From Baseline in EoEHSS Mean Stage Score at Week 24

  Baseline and week 24

• Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 24

  Baseline and week 24

Study Arms (3)

Part A: Dupilumab or Placebo

EXPERIMENTAL

Part A consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.

Drug: Dupilumab; Drug: Placebo

Part B: Dupilumab or Placebo

EXPERIMENTAL

Part B consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab dosing regimen 1, dupilumab dosing regimen 2 or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.

Drug: Dupilumab; Drug: Placebo

Part C: Dupilumab

EXPERIMENTAL

Part C is a 28-week extended active treatment period. Participants will receive dupilumab dosing regimen 1, dupilumab dosing regimen 2. At the end of the treatment period (week 52), participants will enter a 12-week follow-up period.

Drug: Dupilumab

Interventions

Dupilumab DRUG

Solution for injection administered subcutaneously

Also known as: DUPIXENT, REGN668, SAR231893

Part A: Dupilumab or Placebo; Part B: Dupilumab or Placebo; Part C: Dupilumab

Placebo DRUG

Matching placebo

Part A: Dupilumab or Placebo; Part B: Dupilumab or Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (95)

Regeneron Study Site

Phoenix, Arizona, 85016, United States

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Scottsdale, Arizona, 85259, United States

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Little Rock, Arkansas, 72202, United States

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La Jolla, California, 92037, United States

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Los Angeles, California, 90025, United States

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Mountain View, California, 94305, United States

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Orange, California, 92868, United States

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Rolling Hills Estates, California, 90274, United States

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San Diego, California, 92123, United States

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Aurora, Colorado, 80045, United States

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Aurora, Colorado, 80220, United States

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Colorado Springs, Colorado, 80907, United States

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Lone Tree, Colorado, 80124, United States

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Bristol, Connecticut, 06010, United States

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Miami, Florida, 33156, United States

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St. Petersburg, Florida, 33701, United States

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Boise, Idaho, 83706, United States

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Idaho Falls, Idaho, 83404, United States

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Regeneron Study Site #1

Chicago, Illinois, 60611, United States

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Regeneron Study Site #2

Chicago, Illinois, 60611, United States

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Park Ridge, Illinois, 60068, United States

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Urbana, Illinois, 61801, United States

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Indianapolis, Indiana, 46202, United States

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Clive, Iowa, 50325, United States

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Iowa City, Iowa, 52242, United States

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Topeka, Kansas, 66606, United States

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Hagerstown, Maryland, 21742, United States

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Boston, Massachusetts, 02111, United States

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Worcester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48109, United States

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Chesterfield, Michigan, 48047, United States

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Plymouth, Minnesota, 55446, United States

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Rochester, Minnesota, 55905, United States

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Lincoln, Nebraska, 68505, United States

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Omaha, Nebraska, 68130, United States

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Great Neck, New York, 11021, United States

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Great Neck, New York, 11023, United States

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New York, New York, 10016, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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The Bronx, New York, 10461, United States

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Chapel Hill, North Carolina, 27599, United States

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Cincinnati, Ohio, 45229, United States

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Dayton, Ohio, 45415, United States

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Dublin, Ohio, 43016, United States

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Mentor, Ohio, 44060, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29425, United States

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Greenville, South Carolina, 29615, United States

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Johnson City, Tennessee, 37604, United States

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Memphis, Tennessee, 38103, United States

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Dallas, Texas, 75207, United States

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Fort Worth, Texas, 76104, United States

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Garland, Texas, 75044, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78229, United States

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Salt Lake City, Utah, 84132, United States

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Charlottesville, Virginia, 22903, United States

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Roanoke, Virginia, 24013, United States

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Seattle, Washington, 98115, United States

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Milwaukee, Wisconsin, 53226, United States

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Camperdown, New South Wales, 2050, Australia

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Woolloongabba, Queensland, 4102, Australia

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Elizabeth Vale, South Australia, 5112, Australia

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Melbourne, Victoria, 3052, Australia

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Bruges, 8310, Belgium

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Edegem, 2650, Belgium

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Leuven, 03000, Belgium

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London, Ontario, N6A5W9, Canada

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Ottawa, Ontario, K1G6S6, Canada

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Montreal, Quebec, H3T1C5, Canada

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Hamilton, L8S 1G5, Canada

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Pessac, 33604 Cedex, France

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Toulouse, TSA 50032-31059, France

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Hanover, 30459, Germany

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Magdeburg, 39120, Germany

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Munich, 81675, Germany

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Genoa, 16132, Italy

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Milan, 20122, Italy

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Naples, 80100, Italy

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Pisa, 56124, Italy

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Rome, 00161, Italy

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Rome, 00165, Italy

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Rozzano, 20089, Italy

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Amsterdam, 1105 AZ, Netherlands

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Maastricht, 6229HX, Netherlands

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Nijmegen, 6525GA, Netherlands

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Tomelloso, Ciudad Real, 13700, Spain

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Barcelona, 08036, Spain

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Madrid, 28006, Spain

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Stockholm, 141 86, Sweden

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Zurich, CH-8091, Switzerland

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London, Whitechapel, E1 1BB, United Kingdom

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Barnsley, Yorkshire, S752EP, United Kingdom

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Related Publications (6)

• Bredenoord AJ, Dellon ES, Schlag C, Cianferoni A, Xia C, Pela T, Durrani S, Radwan A, Jacob-Nara JA. Dupilumab is efficacious for eosinophilic esophagitis irrespective of prior swallowed budesonide or fluticasone, or prior treatments used alongside swallowed topical corticosteroids: results from the phase 3, randomized, placebo-controlled, LIBERTY EoE TREET trial. Expert Rev Gastroenterol Hepatol. 2025 Jan-Feb;19(2):197-209. doi: 10.1080/17474124.2025.2461516. Epub 2025 Feb 5.

  PMID: 39909733 DERIVED

• Spergel JM, Chehade M, Dellon ES, Bredenoord AJ, Sun X, Glotfelty L, Shabbir A, Tilton ST, McCann E. Dupilumab Improves Health-Related Quality of Life and a Range of Symptoms in Patients With Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 1;119(12):2398-2407. doi: 10.14309/ajg.0000000000002924. Epub 2024 Jun 28.

  PMID: 38940435 DERIVED

• Bredenoord AJ, Dellon ES, Hirano I, Lucendo AJ, Schlag C, Sun X, Glotfelty L, Mannent L, Maloney J, Laws E, Mortensen E, Shabbir A. Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study. Gut. 2024 Feb 23;73(3):398-406. doi: 10.1136/gutjnl-2023-330220.

  PMID: 38050037 DERIVED

• McCann E, Chehade M, Spergel JM, Yaworsky A, Symonds T, Stokes J, Tilton ST, Sun X, Kamat S. Validation of the novel Eosinophilic Esophagitis Impact Questionnaire. J Patient Rep Outcomes. 2023 Nov 27;7(1):120. doi: 10.1186/s41687-023-00654-z.

  PMID: 38010430 DERIVED

• Rothenberg ME, Dellon ES, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Sun X, Hamilton JD, Mortensen E, Laws E, Maloney J, Mannent LP, McCann E, Liu X, Glotfelty L, Shabbir A. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2023 Nov;8(11):990-1004. doi: 10.1016/S2468-1253(23)00204-2. Epub 2023 Aug 31.

  PMID: 37660704 DERIVED

• Dellon ES, Rothenberg ME, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Aceves S, Sun X, Kosloski MP, Kamal MA, Hamilton JD, Beazley B, McCann E, Patel K, Mannent LP, Laws E, Akinlade B, Amin N, Lim WK, Wipperman MF, Ruddy M, Patel N, Weinreich DR, Yancopoulos GD, Shumel B, Maloney J, Giannelou A, Shabbir A. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022 Dec 22;387(25):2317-2330. doi: 10.1056/NEJMoa2205982.

  PMID: 36546624 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 Trials Administrator
• 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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 16, 2018
• Study Start: September 24, 2018
• Primary Completion: September 9, 2021
• Study Completion: June 7, 2022
• Last Updated: June 28, 2023
• Results First Posted: December 28, 2022

Record last verified: 2023-06

Locations

SE (1); US (62); IT (7); CH (1); CA (4); AU (4); GB (2); NL (3); FR (2); ES (3); DE (3); BE (3)