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

• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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 Design

• 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: May 18, 2022
• Estimated Study Completion Date: March 14, 2023

Arms and Interventions

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 may 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 may 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 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; Solution for injection administered subcutaneously; Other Names: DUPIXENT; REGN668; SAR231893

Outcome Measures

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 Grade Score from the 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 EoE Grade Score from the 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. Absolute change in EoE Stage Score from the 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).
10. Absolute change in EoE Stage Score from the 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).
11. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 24 ]
12. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 52 ]
13. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 24 ]
14. Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 52 ]
15. 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.
16. 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.
17. 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
18. 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.
19. Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 24 ]
20. Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 52 ]
21. Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 24 ]
22. Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 52 ]
23. Absolute change in esophageal distensibility plateau measured by functional lumen imagining [ Time Frame: Baseline to week 24 ]
    A catheter-based procedure that measures the cross-sectional area at multiple sites along the esophagus.
24. Absolute change in esophageal distensibility plateau measured by functional lumen imagining [ Time Frame: Baseline to week 52 ]
    A catheter-based procedure that measures the cross-sectional area at multiple sites along the esophagus.

Eligibility Criteria

• 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):

• 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

Contacts and Locations

Contacts

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

  Show 35 Study Locations

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• 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
• Last Update Posted: June 18, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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