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

Eosinophilic Gastritis Clinical Trial

— ENGAGE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05831176
• Other study ID #: R668-EGE-2213
• Secondary ID: 2022-500795-62-0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 3, 2023
• Est. completion date: August 19, 2027

Study information

• Verified date: November 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 279
• Est. completion date: August 19, 2027
• Est. primary completion date: August 19, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Diseases
• Duodenitis
• Enteritis
• Eosinophilia
• Eosinophilic Duodenitis
• Eosinophilic Esophagitis
• Eosinophilic Gastritis
• Gastritis
• Gastrointestinal Diseases

Intervention

Drug:
• Dupilumab Dose 1
Administered subcutaneously (SC) once weekly (QW)
• Dupilumab Dose 2
Administered SC once every 2 weeks (Q2W)
• Matching Placebo
Administered SC

Locations

Country	Name	City	State
Australia	St. Vincent's Hospital	Fitzroy
Australia	Joondalup Health campus	Joondalup
Australia	Coral Sea Clinical Research Institute	North Mackay
Australia	The University of Queensland - Princess Alexandra Hospital (PAH)	Woolloongabba	Queensland
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Ospedale S Giovanni Calibita Fatebenefratelli Isola Tiberina	Roma
Italy	Sapienza - University of Rome	Rome
Italy	IRCCS Istituto clinico humanitas - Humanitas Mirasole spa	Rozzano
Japan	Hyogo Prefectural Harima-Himeji General Medical Center	Himeji	Hyogo
Japan	Isesaki Municipal Hospital	Isesaki-shi	Gunma
Japan	Kobe University Hospital	Kobe-shi	Hyogo
Japan	Kawasaki Medical School Hospital	Kurashiki City	Okayama
Japan	Kure Kyosai Hospital	Kure-shi	Hiroshima
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Poland	Korczowski Bartosz, Gabinet Lekarski	Rzeszow
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warsaw
Poland	Centrum Medyczne Melita Medical	Wroclaw
United States	University of Michigan	Ann Arbor	Michigan
United States	Om Research LLC	Apple Valley	California
United States	Beth Israel Deaconess Medical Center (BIDMC) Harvard Medical School	Boston	Massachusetts
United States	Boston Specialists	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Connecticut Clinical Research Institute	Bristol	Connecticut
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina
United States	Uconn Health	Farmington	Connecticut
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	GI Alliance	Garland	Texas
United States	Long Island Gastrointestinal Research Group	Great Neck	New York
United States	Northwell Health	Great Neck	New York
United States	GI Alliance - Gurnee	Gurnee	Illinois
United States	Meritus Center for Clinical Research	Hagerstown	Maryland
United States	Galen Medical Group	Hixson	Tennessee
United States	The University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	Encore Borland-Groover Clinical Research	Jacksonville	Florida
United States	University Of Kansas	Kansas City	Kansas
United States	ESI Medical Research, PLLC	Kinston	North Carolina
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	Om Research LLC	Lancaster	California
United States	Laredo Medical Center	Laredo	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	United Gastroenterologists	Los Alamitos	California
United States	GastroIntestinal BioSciences	Los Angeles	California
United States	USC, Keck School of Medicine	Los Angeles	California
United States	TDDC dba GI Alliance Research	Mansfield	Texas
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	United Medical Doctors	Murrieta	California
United States	Allergy, Asthma and Clinical Research Center	Oklahoma City	Oklahoma
United States	Children's Hospital & Medical Center	Omaha	Nebraska
United States	The Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	Advanced Research Institute	Reno	Nevada
United States	The University of Utah Health Sciences Center	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Seattle Allergy and Asthma Research Institute	Seattle	Washington
United States	Velocity Clinical Research	West Jordan	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Japan,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in frequency of diarrhea epispodes	Assessed for only those with diarrhea at baseline.	Baseline at Week 24 and Baseline at Week 52
Secondary	Change in frequency of vomiting episodes	Assessed for only those with vomiting at baseline	Baseline at Week 24 and Baseline at Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of participants who receive rescue medications or procedures	Part A, Part B and Part C	At Week 24 and At Week 52
Secondary	Proportion of participants achieving a peak gastric eosinophil count of =6 eos/hpf	Part C	At Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Welcome to Engage! Clinical research study for eosinophilic gastritis with or without eosinophilic duodenitis