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

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ClinicalTrials.gov Identifier: NCT03633617
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : October 29, 2019
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 14, 2018
First Posted Date  ICMJE August 16, 2018
Last Update Posted Date October 29, 2019
Actual Study Start Date  ICMJE September 24, 2018
Estimated Primary Completion Date May 18, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 24 ]
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03633617 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 52 ]
  • 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.
  • 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.
  • 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.
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 24 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 52 ]
  • 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).
  • 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).
  • 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).
  • 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).
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 24 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 52 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 24 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 52 ]
  • 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.
  • 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.
  • 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
  • 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.
  • Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 24 ]
  • Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 52 ]
  • Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 24 ]
  • Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 52 ]
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2018)
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 52 ]
  • 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.
  • 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.
  • 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.
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 24 ]
  • Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: Baseline to week 52 ]
  • Absolute change in EoE Histology Scoring System (EoEHSS) [ Time Frame: Baseline to week 24 ]
  • Absolute change in EoE Histology Scoring System (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).
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 24 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 52 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 24 ]
  • Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 52 ]
  • 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.
  • 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.
  • 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
  • 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.
  • Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: Baseline to week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
Official Title  ICMJE A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Eosinophilic Esophagitis
Intervention  ICMJE
  • Drug: Dupilumab
    Solution for injection administered subcutaneously
    Other Names:
    • DUPIXENT
    • REGN668
    • SAR231893
  • Drug: Placebo
    Matching placebo
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Dupilumab
    • Drug: 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.
    Interventions:
    • Drug: Dupilumab
    • Drug: 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.
    Intervention: Drug: Dupilumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 14, 2018)
425
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 14, 2023
Estimated Primary Completion Date May 18, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03633617
Other Study ID Numbers  ICMJE R668-EE-1774
2018-000844-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP