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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

Phase 2
Recruiting
Conditions
Eosinophilic Gastritis (EoG)
Eosinophilic Duodenitis (EoD)
Eosinophilic Gastrointestinal Disease (EGID)
Eosinophilic Gastroenteritis
Interventions
Registration Number
NCT05831176
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

This 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 after at least 24 weeks (about 6 months) and up to 52 weeks (1 year) of treatment.

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 the 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 study has 2 parts and a 12-week (about 3 months) Follow-up Period for all participants

* Part A is an open-label treatment period lasting up to 24 weeks (up to 6 months). "Open-label" means that you and the study doctors and the staff staff will know that you are taking the study drug

* Part C is an open-label extended treatment period lasting up to 28 weeks (about 7 months). "Extended Treatment Period" means that you will take the study drug for 28 weeks if you are eligible to take part in this part of the study

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
22
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. 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 TSS 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.

Key

Exclusion Criteria
  1. Body weight less than 40 kg at screening
  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, as defined in the protocol
  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

NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
DupilumabDupilumabPart A: Treatment Period Part C: Extended Treatment Period Eligible participants from Part A will enter Part C
Primary Outcome Measures
NameTimeMethod
Percent change in peak gastric eosinophil count eosinophils/high power field (eos/hpf)Baseline to Week 24
Secondary Outcome Measures
NameTimeMethod
Proportion of participants achieving a peak gastric eosinophil count of ≤20 eos/hpfUp to 52 Weeks
Proportion of participants achieving a peak gastric eosinophil count of ≤30 eos/hpfUp to 52 Weeks
Proportion of participants achieving a peak duodenal eosinophil count of ≤30 eos/hpfUp to 52 Weeks

Assessed for only those with duodenal involvement

Titer of ADAUp to 52 Weeks

Immunogenicity will be characterized per drug molecule by ADA status

Incidence of neutralizing antibody (NAb) to dupilumabUp to 52 Weeks

Immunogenicity will be characterized per drug molecule by NAb status

Incidence of treatment-emergent serious adverse events (SAEs)Up to 52 Weeks

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

Change in frequency of vomiting episodesBaseline up to 52 Weeks

Assessed for only those with vomiting at baseline

Change in the Normalized Enrichment Scores (NES) for the type 2 inflammation transcriptome signatureBaseline up to 52 Weeks

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 signatureBaseline up to 52 Weeks

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 signatureBaseline up to 52 Weeks

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 proceduresUp to 52 Weeks
Incidence of treatment-emergent adverse events (TEAEs)Up to 52 Weeks

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 adverse events of special interest (AESIs)Up to 52 Weeks

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 treatmentUp to 52 Weeks

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)Up to 52 Weeks

Immunogenicity will be characterized per drug molecule by ADA status

Concentrations of functional dupilumab in serum at each assessment time pointBaseline to 64 Weeks

The concentrations of functional dupilumab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients.

Proportion of participants achieving both a peak gastric eosinophil count of ≤20 eos/hpf and a peak duodenal eosinophil count of ≤30 eos/hpfUp to 52 Weeks
Absolute change in the EoG/EoD-SQ Total Symptom Score (TSS)Baseline up to 52 Weeks

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 TSSBaseline up to 52 Weeks
Percent change in peak duodenal tissue eosinophil count (eos/hpf)Baseline up to 52 Weeks

Assessed for only those with duodenal involvement

Absolute change in EoG scores from the EoG Histology Scoring System (EoGHSS)Baseline up to 52 Weeks

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 episodesBaseline up to 52 Weeks

Assessed for only those with diarrhea at baseline

Trial Locations

Locations (78)

Om Research LLC

🇺🇸

Lancaster, California, United States

Scripps Memorial Hospital La Jolla

🇺🇸

La Jolla, California, United States

University of California - Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

Gi Alliance

🇺🇸

Gurnee, Illinois, United States

Meritus Medical Center

🇺🇸

Hagerstown, Maryland, United States

Mayo Clinic Hospital Rochester

🇺🇸

Rochester, Minnesota, United States

Children's Hospital and Medical Center

🇺🇸

Omaha, Nebraska, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

GI Alliance Research - Garland

🇺🇸

Garland, Texas, United States

Envision Clinical Research Lcc

🇺🇸

Laredo, Texas, United States

Stollery Children's Hospital - University of Alberta

🇨🇦

Edmonton, Alberta, Canada

AOOR Villa Sofia/Cervello

🇮🇹

Palermo, Sicilia, Italy

Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Italy

University of Rome - Pediatric Gastroenterology and Liver Unit

🇮🇹

Rome, Italy

Korczowski Bartosz - Gabinet Lekarski

🇵🇱

Rzeszow, Podkarpackie, Poland

Phoenix Childrens Hospital

🇺🇸

Phoenix, Arizona, United States

United Gastroenterologists

🇺🇸

Los Alamitos, California, United States

USC, Keck School of Medicine

🇺🇸

Los Angeles, California, United States

GastroIntestinal BioSciences

🇺🇸

Los Angeles, California, United States

United Medical Doctors

🇺🇸

Murrieta, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Connecticut Clinical Research Institute

🇺🇸

Bristol, Connecticut, United States

Uconn Health

🇺🇸

Farmington, Connecticut, United States

Encore Borland-Groover Clinical Research

🇺🇸

Jacksonville, Florida, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

The University of Iowa Hospitals & Clinics

🇺🇸

Iowa City, Iowa, United States

University Of Kansas

🇺🇸

Kansas City, Kansas, United States

Boston Specialists

🇺🇸

Boston, Massachusetts, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center (BIDMC) Harvard Medical School

🇺🇸

Boston, Massachusetts, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Minnesota Gastroenterology, P.A.

🇺🇸

Plymouth, Minnesota, United States

Advanced Research Institute

🇺🇸

Reno, Nevada, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Northwell Health

🇺🇸

Great Neck, New York, United States

Long Island Gastrointestinal Research Group

🇺🇸

Great Neck, New York, United States

Icahn School of Medicine at Mount Sinai (ISMMS) - The Mount Sinai Hospital (MSH)

🇺🇸

New York, New York, United States

Charlotte Gastroenterology & Hepatology, PLLC

🇺🇸

Charlotte, North Carolina, United States

Duke University Health System

🇺🇸

Durham, North Carolina, United States

Azienda Ospedaliero Universitaria Pisana

🇮🇹

Pisa, Italy

ESI Medical Research, PLLC

🇺🇸

Kinston, North Carolina, United States

University of Cincinnati Medical Center-Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

Great Lakes Gastroenterology Research, LLC

🇺🇸

Mentor, Ohio, United States

Allergy, Asthma and Clinical Research Center

🇺🇸

Oklahoma City, Oklahoma, United States

The Oregon Clinic - Gastroenterology East

🇺🇸

Portland, Oregon, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Galen Medical Group

🇺🇸

Hixson, Tennessee, United States

Vanderbilt University Medical Center-Digestive Disease Center

🇺🇸

Nashville, Tennessee, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

TDDC dba GI Alliance Research

🇺🇸

Mansfield, Texas, United States

The University of Utah Health Sciences Center

🇺🇸

Salt Lake City, Utah, United States

Velocity Clinical Research

🇺🇸

West Jordan, Utah, United States

Seattle Children's Home Health Company

🇺🇸

Seattle, Washington, United States

Seattle Allergy and Asthma Research Institute

🇺🇸

Seattle, Washington, United States

Froedtert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

Nepean Hospital

🇦🇺

Kingswood, New South Wales, Australia

Mater Research Ltd

🇦🇺

South Brisbane, Queensland, Australia

The University of Queensland - Princess Alexandra Hospital (PAH)

🇦🇺

Woolloongabba, Queensland, Australia

St. Vincent's Hospital

🇦🇺

Fitzroy, Australia

Joondalup Health Campus

🇦🇺

Joondalup, Australia

Coral Sea Clinical Research Institute

🇦🇺

North Mackay, Australia

Humanitas Research Hospital

🇮🇹

Rozzano, Milan, Italy

U.O. Di Ematologia-Azienda Policlinico Consorziale, Ospedaliero-Universitaria, Ospedale

🇮🇹

Bari, Italy

Ospedale S Giovanni Calibita Fatebenefratelli Isola Tiberina

🇮🇹

Roma, Italy

Iizuka Hospital

🇯🇵

Iizuka, Fukuoka, Japan

Ogaki Municipal Hospital

🇯🇵

Ogaki, Gifu, Japan

Isesaki Municipal Hospital

🇯🇵

Isesaki, Gunma, Japan

Kure Kyosai Hospital

🇯🇵

Kure, Hiroshima, Japan

Hyogo Prefectural Harima-Himeji General Medical Center

🇯🇵

Himeji, Hyogo, Japan

Kobe University Hospital

🇯🇵

Kobe-shi, Hyogo, Japan

Yokohama City University Hospital

🇯🇵

Yokohama-shi, Kanagawa, Japan

Kawasaki Medical School Hospital

🇯🇵

Kurashiki, Okayama, Japan

Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital

🇯🇵

Minato-ku, Tokyo, Japan

Yamagata University Hospital

🇯🇵

Yamagata, Japan

Wip Warsaw Ibd Point Profesor Kierkus

🇵🇱

Warszawa, Mazowieckie, Poland

Centrum Medyczne Melita Medical

🇵🇱

Wroclaw, Poland

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