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

JRCT ID: jRCT2031230539

Registered date:26/12/2023

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

- Eosinophilic Gastritis
- Eosinophilic Duodenitis
- Eosinophilic Gastrointestinal Disease

• Date of first enrollment: 01/02/2024
• Target sample size: 32
• Countries of recruitment: US,Japan,Canada,Japan,Italy,Japan,Poland,Japan,Australia,Japan,France,Japan
• Study type: Interventional

Intervention(s)

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

- Drug: Dupilumab Dose 1
- Drug: Dupilumab Dose 2
- Drug: Matching Placebo

Outcome(s)

Primary Outcome

-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.

Secondary Outcome

-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.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include 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.
NOTE: Other Protocol Defined Inclusion Criteria Apply

Exclude 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 Exclusion Criteria Apply

Related Information

• Primary Sponsor: Shabbir Arsalan Q.
• Secondary ID(s): NCT05831176,2022-500795-62-00