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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Eosinophilic Gastritis, Eosinophilic Duodenitis, Eosinophilic Gastrointestinal Disease

Intervention / Treatment
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* Drug: Dupilumab Dose 1
* Drug: Dupilumab Dose 2
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adolescent participants will only be enrolled at study sites in countries/regions as permitted by local regulatory authorities and ethic committees (ECs) Documented endoscopic biopsy supporting a pathologic diagnosis of Eosinophilic gastritis (EoG) at least 3 months prior to screening Baseline endoscopic biopsies with a demonstration of eosinophilic infiltration for a diagnosis of EoG, as defined in the protocol Completed at least 11 of 14 days of EoG/EoD-SQ eDiary data entry in the 2 weeks prior to the baseline visit History (by patient report) of at least 2 episodes of EoG (with or without EoD) symptoms per week in 8 weeks before screening 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: Body weight less than 40 kg Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab Helicobacter pylori infection Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening History of achalasia, Crohn's disease, eosinophilic colitis, ulcerative colitis, celiac disease, and prior gastric or duodenal surgery Other causes of gastric and, if applicable, duodenal eosinophilia or the following conditions: eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or hyper-eosinophilic syndrome 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 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 Planned or anticipated use of any prohibited medications and procedures during the study Planned or anticipated major surgical procedure during the study Receiving tube feeding or parenteral nutritional at screening (Part A and B). NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Phase 2<br>Randomized 1:1 | Drug: Dupilumab Dose 1<br>* Administered subcutaneously (SC) once weekly (QW)<br>* Other names: SAR231893;Drug: Matching Placebo<br>* Administered SC<br>|
| Experimental: Part B: Phase 3<br>Randomized 1:1:1 | Drug: Dupilumab Dose 1<br>* Administered subcutaneously (SC) once weekly (QW)<br>* Other names: SAR231893;Drug: Dupilumab Dose 2<br>* Administered SC once every 2 weeks (Q2W)<br>* Other names: SAR231893;Drug: Matching Placebo<br>* Administered SC<br>|
| Experimental: Part C: Extended Active Treatment Period<br>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. | Drug: Dupilumab Dose 1<br>* Administered subcutaneously (SC) once weekly (QW)<br>* Other names: SAR231893;Drug: Dupilumab Dose 2<br>* Administered SC once every 2 weeks (Q2W)<br>* Other names: SAR231893;Drug: Matching Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving a peak gastric eosinophil count of ≤6 eosinophils/high power field (eos/hpf) | Part A and Part B | At Week 24 | 
| Absolute change in the Eosinophilic Gastritis/Eosinophilic Duodenitis Symptom Questionnaire (EoG/EoD-SQ) Total Symptom Score (TSS) | 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. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving both a peak gastric eosinophil count of ≤6 eos/hpf and a peak duodenal eosinophil count of ≤15 eos/hpf | Part A, Part B and Part C | At Week 24 and At Week 52 | 
| Proportion of participants achieving a peak duodenal eosinophil count of ≤15 eos/hpf | Part A, Part B and Part C | At Week 24 and At Week 52 | 
| Absolute change in the EoG/EoD-SQ TSS | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Percent change in the EoG/EoD-SQ TSS | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Percent change in peak gastric tissue eosinophil count (eos/hpf) | Part A, Part B and Part C | Baseline to Week 24 and Baseline to Week 52 | 
| Proportion of participants achieving a peak gastric tissue eosinophil count of <30 eos/hpf | Part A, Part B and Part C | At Week 24 and At Week 52 | 
| Percent change in peak duodenal tissue eosinophil count (eos/hpf) | Part A, Part B and Part C: Assessed for only those with duodenal involvement | Baseline to Week 24 and Baseline to Week 52 | 
| Proportion of participants achieving a peak duodenal tissue eosinophil count of <30 eos/hpf | Part A, Part B and Part C: Assessed for only those with duodenal involvement | At Week 24 and At Week 52 | 
| Absolute change in EoG scores from the EoG Histology Scoring System (EoGHSS) | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Change in frequency of diarrhea epispodes | Assessed for only those with diarrhea at baseline. | Baseline at Week 24 and Baseline at Week 52 | 
| Change in frequency of vomiting episodes | Assessed for only those with vomiting at baseline | Baseline at Week 24 and Baseline at Week 52 | 
| Change in the Normalized Enrichment Scores (NES) for the type 2 inflammation transcriptome signature | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Change in the NES for the type 2 inflammation transcriptome signature | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Change in the NES for the EoG disease (EoG diagnostic panel (EGDP]) transcriptome signature | 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. | Baseline to Week 24 and Baseline to Week 52 | 
| Proportion of participants who receive rescue medications or procedures | Part A, Part B and Part C | At Week 24 and At Week 52 | 
| Proportion of participants achieving a peak gastric eosinophil count of ≤6 eos/hpf | Part C | At Week 52 | 
| Incidence of treatment-emergent adverse events (TEAEs) | 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. | Up to Week 52 | 
| Incidence of treatment-emergent serious adverse events (SAEs) | 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 | Up to Week 52 | 
| Incidence of treatment-emergent adverse events of special interest (AESIs) | 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 | Up to Week 52 | 
| Incidence of TEAEs leading to permanent discontinuation of study treatment | 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. | Up to Week 52 | 
| Incidence of anti-drug antibody (ADA) | Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status | Up to Week 52 | 
| Titer of ADA | Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status | Up to Week 52 | 
| Incidence of neutralizing antibody (Nab) to dupilumab | Part A, Part B and Part C Immunogenicity will be characterized per drug molecule by ADA and NAb status | Up to Week 52 | 
| Concentrations of functional dupilumab in serum at each assessment time point from baseline to end of study | The concentrations of functional dupilumab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients. | Baseline to Week 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eosinophilic Gastritis (EoG) with or without Eosinophilic Duodenitis (EoD), Eosinophilic Gastrointestinal Disease (EGID)