A Study to Learn How Well Dupilumab Works in Adult and Adolescent Participants with Eosinophilic Gastritis with or without Eosinophilic Duodenitis and the Side Effects it May Have

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

25 Mar 2024 → ongoing

Decision date (initial)

2024-01-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-500795-62-00

ClinicalTrials.gov

NCT05831176

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of dupilumab treatment in adult and adolescent participants with eosinophilic gastritis (EoG) with or
without eosinophilic duodenitis (EoD) after 24 weeks of treatment as assessed by histological outcome measures.

Secondary objectives 5

1. To assess the efficacy of dupilumab treatment in adult and adolescent participants with EoG (with or without EoD) after 24 weeks of treatment as assessed by clinical measures.
2. To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent participants with EoG (with or without EoD)
3. To characterize the trough concentrations of functional dupilumab over time following administration of dupilumab in adult and adolescent participants with EoG (with or without EoD)
4. To evaluate the effects of dupilumab on transcriptomic signatures associated with EoG (with or without EoD) and type 2 inflammation
5. To assess the efficacy of dupilumab treatment in adult and adolescent participants with EoG (with or without EoD) after up to 52 weeks of treatment as assessed by histological and clinical measures

Conditions and MedDRA coding

Eosinophilic gastritis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female, ≥12 years of age (Adolescent participants will only be enrolled at study sites in countries/regions as permitted by local regulatory authorities or ethic committees (ECs))
2. Documented endoscopic biopsy supporting a pathologic diagnosis of EoG at least 3 months prior to screening.
3. Screening 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 participant report) of at least 2 episodes of EoG (with or without EoD) symptoms per week in 8 weeks before screening, as defined in the protocol
6. An average TTS of 20 calculated using data collected via the EoG/EoD-SQ eDiary per week for the 2 weeks prior to baseline. An average severity score of ≥4 (on a scale of 0-10) per week for the 2 weeks prior to baseline for at least 2 of the 6 symptoms, as defined in the protocol
7. NOTE: Other protocol defined inclusion criteria apply

Exclusion criteria 12

1. Body weight <40 kg at screening
2. Planned or anticipated major surgical procedure during the study
3. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
4. Helicobacter pylori infection
5. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
6. History of achalasia, Crohn’s disease, eosinophilic colitis, ulcerative colitis, celiac disease, and prior gastric or duodenal surgery, as defined in the protocol
7. Other causes of gastric and, if applicable, duodenal eosinophilia or the following conditions: eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or hyper-eosinophilic syndrome
8. 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
9. Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 4 weeks prior to screening. Participants on a food-elimination diet must remain on the same diet throughout the study.
10. Planned or anticipated use of any prohibited medications and procedures during the study
11. Receiving tube feeding or parenteral nutritional at screening
12. NOTE: Other protocol defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in peak gastric tissue eosinophil count (eos/hpf) from baseline to week 24

Secondary endpoints 16

1. Proportion of participants achieving a peak gastric eosinophil count of ≤20 eos/hpf up to 52 weeks
2. Proportion of participants achieving a peak gastric tissue eosinophil count of <30 eos/hpf up to 52 weeks
3. Proportion of participants achieving both a peak gastric eosinophil count of ≤20 eos/hpf and a peak duodenal eosinophil count <30 eos/hpf up to 52 weeks(assessed for those with both gastric and duodenal involvement)
4. Proportion of participants achieving a peak duodenal eosinophil count of <30 eos/hpf up to 52 weeks (assessed for those with duodenal involvement)
5. Absolute change in the EoG/EoD-SQ TSS from baseline up to 52 weeks
6. Percent change in the EoG/EoD-SQ TSS from baseline up to 52 weeks
7. Percent change in peak duodenal tissue eosinophil count (eos/hpf) from baseline up to 52 weeks (assessed for those with duodenal involvement)
8. Absolute change in EoG scores from the EoG Histology Scoring System (EoGHSS) from baseline up to 52 weeks
9. Change from baseline in frequency of diarrhea episodes up to 52 weeks (assessed for only those with diarrhea at baseline)
10. Change from baseline in frequency of vomiting episodes up to 52 weeks (assessed for only those with vomiting at baseline)
11. Change from baseline up to 52 weeks in the Normalized Enrichment Scores (NES) for the type 2 inflammation transcriptome signature (assessed on gastric tissue)
12. Change from baseline up to 52 weeks in the NES for the type 2 inflammation transcriptome signature (assessed on duodenal tissue from participants with EoD)
13. Change from baseline up to 52 weeks in the NES for the EoG disease (EoG diagnostic panel [EGDP]) transcriptome signature (assessed on gastric tissue)
14. Percent change in peak gastric tissue eosinophil count (eos/hpf) from baseline to week 52
15. Proportion of participants who receive rescue medications or procedures up to 52 weeks
16. Other secondary endpoints are specified within the protocol

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 13

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications