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A Trial to Learn if Dupilumab is Safe for and Helps Adult and Adolescent Participants With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis (ENGAGE)

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: NCT05831176
Recruitment Status : Recruiting
First Posted : April 26, 2023
Last Update Posted : April 12, 2024
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 14, 2023
First Posted Date  ICMJE April 26, 2023
Last Update Posted Date April 12, 2024
Actual Study Start Date  ICMJE May 3, 2023
Estimated Primary Completion Date August 19, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2023)
  • Proportion of participants achieving a peak gastric eosinophil count of ≤6 eosinophils/high power field (eos/hpf) [ Time Frame: At Week 24 ]
    Part A and Part B
  • Absolute change in the Eosinophilic Gastritis/Eosinophilic Duodenitis Symptom Questionnaire (EoG/EoD-SQ) Total Symptom Score (TSS) [ Time Frame: Baseline to Week 24 ]
    Part B Only EoG/EoD-SQ is a patient reported outcome (PRO) collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2023)
  • Proportion of participants achieving a peak gastric eosinophil count of ≤6 eos/hpf [ Time Frame: At Week 24 ]
    Part A and Part B
  • Absolute change in the Eosinophilic Gastritis/Eosinophilic Duodenitis Symptom Questionnaire (EoG/EoD-SQ) Total Symptom Score (TSS) [ Time Frame: Baseline to Week 24 ]
    Part B Only EoG/EoD-SQ is a patient reported outcome (PRO) collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2023)
  • Proportion of participants achieving both a peak gastric eosinophil count of ≤6 eos/hpf and a peak duodenal eosinophil count of ≤15 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak duodenal eosinophil count of ≤15 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Absolute change in the EoG/EoD-SQ TSS [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A and Part C EoG/EoD-SQ is a PRO collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
  • Percent change in the EoG/EoD-SQ TSS [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C EoG/EoD-SQ is a PRO collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
  • Percent change in peak gastric tissue eosinophil count (eos/hpf) [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak gastric tissue eosinophil count of <30 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Percent change in peak duodenal tissue eosinophil count (eos/hpf) [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C: Assessed for only those with duodenal involvement
  • Proportion of participants achieving a peak duodenal tissue eosinophil count of <30 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed for only those with duodenal involvement
  • Absolute change in EoG scores from the EoG Histology Scoring System (EoGHSS) [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C EoGHSS scores evaluate 11 features of gastric tissue. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Total scores range from 0 - 1.
  • Change in frequency of diarrhea epispodes [ Time Frame: Baseline at Week 24 and Baseline at Week 52 ]
    Assessed for only those with diarrhea at baseline.
  • Change in frequency of vomiting episodes [ Time Frame: Baseline at Week 24 and Baseline at Week 52 ]
    Assessed for only those with vomiting at baseline
  • Change in the Normalized Enrichment Scores (NES) for the type 2 inflammation transcriptome signature [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C: Assessed on gastric tissue Normalized Enrichment Score (NES) reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • Change in the NES for the type 2 inflammation transcriptome signature [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C: Assessed on duodenal tissue from participants with EoD NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • Change in the NES for the EoG disease (EoG diagnostic panel (EGDP]) transcriptome signature [ Time Frame: Baseline to Week 24 and Baseline to Week 52 ]
    Part A, Part B and Part C: Assessed on gastric tissue NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • Proportion of participants who receive rescue medications or procedures [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak gastric eosinophil count of ≤6 eos/hpf [ Time Frame: At Week 52 ]
    Part C
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
  • Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C An SAE is any untoward medical occurrence that at any dose:
    • Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger)
    • Is life-threatening
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect
    • Is an important medical event
  • Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
  • Incidence of anti-drug antibody (ADA) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Titer of ADA [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Incidence of neutralizing antibody (Nab) to dupilumab [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Concentrations of functional dupilumab in serum at each assessment time point from baseline to end of study [ Time Frame: Baseline to Week 64 ]
    The concentrations of functional dupilumab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2023)
  • Proportion of participants achieving both a peak gastric eosinophil count of ≤6 eos/hpf and a peak duodenal eosinophil count of ≤15 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak duodenal eosinophil count of ≤15 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Absolute change in the EoG/EoD-SQ TSS [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A and Part C EoG/EoD-SQ is a PRO collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
  • Percent change in the EoG/EoD-SQ TSS [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C EoG/EoD-SQ is a PRO collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60.
  • Percent change in peak gastric tissue eosinophil count (eos/hpf) [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak gastric tissue eosinophil count of <30 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Percent change in peak duodenal tissue eosinophil count (eos/hpf) [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed for only those with duodenal involvement
  • Proportion of participants achieving a peak duodenal tissue eosinophil count of <30 eos/hpf [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed for only those with duodenal involvement
  • Absolute change in EoG scores from the Histology Scoring System (EoGHSS) [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C EoGHSS scores evaluate 11 features of gastric tissue. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Total scores range from 0 - 1.
  • Normalized Enrichment Scores (NES) for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed on gastric tissue Normalized Enrichment Score (NES) reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed on duodenal tissue from participants with EoD NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • NES for the relative change in the EoG disease signature (EGDP) transcriptome signature [ Time Frame: Baseline to Week 24 and At Week 52 ]
    Part A, Part B and Part C: Assessed on gastric tissue NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set.
  • Proportion of participants who receive rescue medications or procedures [ Time Frame: At Week 24 and At Week 52 ]
    Part A, Part B and Part C
  • Proportion of participants achieving a peak gastric eosinophil count of ≤6 eos/hpf [ Time Frame: At Week 52 ]
    Part C
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
  • Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C An SAE is any untoward medical occurrence that at any dose:
    • Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger)
    • Is life-threatening
    • Requires in-patient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect
    • Is an important medical event
  • Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it
  • Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
  • Incidence of anti-drug antibody (ADA) [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Titer of ADA [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Incidence of neutralizing antibody (NAb) to dupilumab [ Time Frame: Up to Week 52 ]
    Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status
  • Concentrations of functional dupilumab in serum at each assessment time point from baseline to end of study [ Time Frame: Baseline to Week 64 ]
    The concentrations of functional dupilumab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial to Learn if Dupilumab is Safe for and Helps Adult and Adolescent Participants With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis
Official Title  ICMJE A Phase 2/3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Gastritis With or Without Eosinophilic Duodenitis
Brief Summary

The study is researching an experimental drug called dupilumab. The study is focused on participants with active eosinophilic gastritis (EoG) with or without eosinophilic duodenitis (EoD). Participants with EoD only are not eligible for enrollment. EoG and EoD are uncommon, persistent, allergic/immune diseases in which eosinophils (a type of white blood cell) gather in large numbers in the stomach and small intestine and cause inflammation and damage.

The aim of the study is to evaluate the effect of dupilumab on relieving EoG (with or without EoD) symptoms and reducing inflammation in the stomach and, if applicable, small intestine in adults and adolescents aged 12 years and older, compared to placebo.

The study is looking at several other research questions, including:

  • What side effects may happen from taking the study drug
  • How much study drug is in your blood at different times
  • Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
Detailed Description

This trial will have 3 parts plus screening and follow-up parts:

  • Parts A and B: Participants will either be included in part A or B. Each is a 24-week double-blind (this means none of the participants, doctors, or other trial staff will know what treatment each participant took) part where participants will receive either dupilumab or a placebo (a placebo looks like a trial drug but does not have any medicine in it).
  • Part C: 28-week extension part that will include participants from parts A and B and all participants will receive dupilumab
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
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 Gastritis
  • Eosinophilic Duodenitis
  • Eosinophilic Gastrointestinal Disease
Intervention  ICMJE
  • Drug: Dupilumab Dose 1
    Administered subcutaneously (SC) once weekly (QW)
    Other Names:
    • DUPIXENT®
    • REGN668
    • SAR231893
  • Drug: Dupilumab Dose 2
    Administered SC once every 2 weeks (Q2W)
    Other Names:
    • DUPIXENT®
    • REGN668
    • SAR231893
  • Drug: Matching Placebo
    Administered SC
Study Arms  ICMJE
  • Experimental: Part A: Phase 2
    Randomized 1:1
    Interventions:
    • Drug: Dupilumab Dose 1
    • Drug: Matching Placebo
  • Experimental: Part B: Phase 3
    Randomized 1:1:1
    Interventions:
    • Drug: Dupilumab Dose 1
    • Drug: Dupilumab Dose 2
    • Drug: Matching Placebo
  • Experimental: Part C: Extended Active Treatment Period
    Eligible participants from Part A and Part B will enter Part C. Part A participants will get Dose 1. Part B participants who received Dose 1 or Dose 2 will remain on Dose 1 or Dose 2. Part B placebo participants will be randomized 1:1 to receive Dose 1 or Dose 2.
    Interventions:
    • Drug: Dupilumab Dose 1
    • Drug: Dupilumab Dose 2
    • Drug: Matching Placebo
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: April 14, 2023)		 279
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 19, 2027
Estimated Primary Completion Date August 19, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Adolescent participants will only be enrolled at study sites in countries/regions as permitted by local regulatory authorities and ethic committees (ECs)
  2. Documented endoscopic biopsy supporting a pathologic diagnosis of Eosinophilic gastritis (EoG) at least 3 months prior to screening
  3. Baseline endoscopic biopsies with a demonstration of eosinophilic infiltration for a diagnosis of EoG, as defined in the protocol
  4. Completed at least 11 of 14 days of EoG/EoD-SQ eDiary data entry in the 2 weeks prior to the baseline visit
  5. History (by patient report) of at least 2 episodes of EoG (with or without EoD) symptoms per week in 8 weeks before screening
  6. For the 2 weeks prior to baseline visit, an average total symptom score (TSS) of at least of 20 calculated using data from the EoG/EoD-SQ eDiary and an average severity score of at least 4 (on a scale of 0-10) per week for at least 2 of the 6 symptoms, as defined in the protocol.

Key Exclusion Criteria:

  1. Body weight less than 40 kg
  2. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
  3. Helicobacter pylori infection
  4. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
  5. History of achalasia, Crohn's disease, eosinophilic colitis, ulcerative colitis, celiac disease, and prior gastric or duodenal surgery
  6. Other causes of gastric and, if applicable, duodenal eosinophilia or the following conditions: eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or hyper-eosinophilic syndrome
  7. History of bleeding disorders, esophageal or gastric varices that, in the opinion of the investigator, would put the participant at undue risk for significant complications from an endoscopy procedure
  8. Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 4 weeks prior to the screening visit. Participants on a food-elimination diet must remain on the same diet throughout the study
  9. Planned or anticipated use of any prohibited medications and procedures during the study
  10. Planned or anticipated major surgical procedure during the study
  11. Receiving tube feeding or parenteral nutritional at screening (Part A and B).

NOTE: Other Protocol Defined 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,   Italy,   Japan,   Poland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05831176
Other Study ID Numbers  ICMJE R668-EGE-2213
2022-500795-62-00 ( Registry Identifier: EUCT 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
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
URL: https://vivli.org/
Current Responsible Party Regeneron Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Regeneron Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date November 2023

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