ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03633617
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : January 18, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: Dupilumab Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 425 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 24, 2018
Estimated Primary Completion Date : March 21, 2022
Estimated Study Completion Date : January 6, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: Part A: Dupilumab or Placebo
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 will enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
Drug: Dupilumab
Solution for injection administered subcutaneously
Other Names:
  • DUPIXENT
  • REGN668
  • SAR231893

Drug: Placebo
Matching placebo

Experimental: Part B: Dupilumab or Placebo
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 will enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
Drug: Dupilumab
Solution for injection administered subcutaneously
Other Names:
  • DUPIXENT
  • REGN668
  • SAR231893

Drug: Placebo
Matching placebo

Experimental: Part C: Dupilumab
Part C is a 28-week 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
Solution for injection administered subcutaneously
Other Names:
  • DUPIXENT
  • REGN668
  • SAR231893




Primary Outcome Measures :
  1. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 24 ]
  2. Absolute change in Dysphagia Symptom Questionnaire (DSQ) score [ Time Frame: Baseline to 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.


Secondary Outcome Measures :
  1. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 52 ]
  2. Absolute change in Dysphagia Symptom Questionnaire (DSQ) score [ Time Frame: Baseline to week 52 ]
    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.

  3. Absolute change in EoE endoscopic reference score (EREFS) [ Time Frame: Baseline to week 24 ]
    EoE esophageal characteristics will be analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease using both overall scores and scores for each individual characteristic. Proximal and distal esophageal regions will be scored separately; the score for each region ranges from 0 to 9 and the overall score ranges from 0 to 18.

  4. Absolute change in EoE endoscopic reference score (EREFS) [ Time Frame: Baseline to week 52 ]
    EoE esophageal characteristics will be analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease using both overall scores and scores for each individual characteristic. Proximal and distal esophageal regions will be scored separately; the score for each region ranges from 0 to 9 and the overall score ranges from 0 to 18.

  5. Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 24 ]
  6. Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 52 ]
  7. Absolute change in EoE Histology Scoring System (EoEHSS) [ Time Frame: Baseline to week 24 ]
    The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).

  8. Absolute change in EoEHSS [ Time Frame: Baseline to week 52 ]
    The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).

  9. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 24 ]
  10. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 52 ]
  11. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 24 ]
  12. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 52 ]
  13. Percent change in DSQ [ Time Frame: Baseline to 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.

  14. Percent change in DSQ [ Time Frame: Baseline to week 52 ]
    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.

  15. Absolute change in health-related quality of life (QOL) as measured by EoE Impact Questionnaire (EoE-IQ) [ Time Frame: Baseline to week 24 ]
    The EoE-IQ is a disease-specific measure of health-related QOL in EoE patients. The EoE-IQ measures EoE impact on emotional, social, work and school, and sleep aspect of a patient

  16. Absolute change in health-related QOL as measured by EoE Impact Questionnaire (EoE-IQ) [ Time Frame: Baseline to week 52 ]
    The EoE-IQ is a disease-specific measure of health-related QOL in EoE patients. The EoE-IQ measures EoE impact on emotional, social, work and school, and sleep aspect of a patient.

  17. Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria (Parts A & B):

  1. A documented diagnosis of EoE by endoscopic biopsy prior to screening
  2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
  3. 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):

  1. Body weight ≤40 kg
  2. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
  3. 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.
  4. Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
  5. Active Helicobacter pylori infection
  6. History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery
  7. 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
  8. History of bleeding disorders or esophageal varices
  9. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Key Exclusion Criteria (Part C):

  1. 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
  2. Participants who became pregnant Part A or Part B
  3. 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)
  4. Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment

Note: Other inclusion/ exclusion criteria apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03633617


Contacts
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
United States, Arkansas
Regeneron Study Site Recruiting
Little Rock, Arkansas, United States, 72202
United States, California
Regeneron Study Site Recruiting
Los Angeles, California, United States, 90025
Regeneron Study Site Recruiting
Mountain View, California, United States, 94305
Regeneron Study Site Recruiting
Rolling Hills Estates, California, United States, 90274
United States, Illinois
Regeneron Study Site Recruiting
Urbana, Illinois, United States, 61801
United States, Indiana
Regeneron Study Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Regeneron Study Site Recruiting
Plymouth, Minnesota, United States, 55446
United States, Ohio
Regeneron Study Site Recruiting
Dublin, Ohio, United States, 43016
Regeneron Study Site Recruiting
Englewood, Ohio, United States, 45415
United States, Texas
Regeneron Study Site Recruiting
Garland, Texas, United States, 75044
Regeneron Study Site Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
Study Director: Clinical Trial Management Regeneron Pharmaceuticals

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03633617     History of Changes
Other Study ID Numbers: R668-EE-1774
2018-000844-25 ( EudraCT Number )
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs