A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved

NCT ID: NCT02605837

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 318 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-07
• Study Completion Date: 2019-02-15

Brief Summary

A study in adolescents and adults with eosinophilic esophagitis (EoE) to measure the histologic response and determine if any reduction in dysphagia is achieved.

Conditions

Eosinophilic Esophagitis (EoE)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral Budesonide Suspension (OBS)

Participants will receive Oral Budesonide Suspension (OBS) 10 milliliter (ml) of 0.2 milligram per milliliter (mg/ml) twice daily up to 16 weeks.

Group Type: EXPERIMENTAL

Oral Budesonide Suspension (OBS)

Intervention Type: DRUG

Oral Budesonide Suspension (OBS) 10 milliliter (ml) of 0.2 milligram per milliliter (mg/ml) twice daily up to 16 weeks.

Placebo

Participants will receive oral dose of 10 ml of placebo matched with the experimental drug twice daily up to 16 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral dose of 10 ml of placebo matched with the experimental drug.

Interventions

Oral Budesonide Suspension (OBS)

Oral Budesonide Suspension (OBS) 10 milliliter (ml) of 0.2 milligram per milliliter (mg/ml) twice daily up to 16 weeks.

Intervention Type: DRUG

Placebo

Oral dose of 10 ml of placebo matched with the experimental drug.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants is able to provide written informed consent (participant, parent or legal guardian, and, as appropriate, participant assent) to participate in the study before completing any study-related procedures.
• Participant is male or female aged 11-55 years, inclusive, at time of consent.
• Participant has histologic evidence of eosinophilic esophagitis (EoE) with a peak eosinophil count of greater than or equal to (>=) 15/ high-powered field (HPF), from 2 of 3 (proximal, mid-, and/or distal) levels of the esophagus at the screening endoscopy.
• Participant has a history of clinical symptoms of esophageal dysfunction (for example, eating problems, abdominal pain, heartburn, dysphagia, vomiting, food impaction, weight loss) intermittently or continuously at screening (Visit -1).
• Participants must have experienced dysphagia (response of "yes" to question 2 on Dysphagia Symptom Questionnaire [DSQ]) on a minimum of 4 days and completed the DSQ on >= 70 percent (%) of days in any 2 consecutive weeks of the screening period and in the last 2 weeks prior to the baseline visit (Visit 1).
• Participant must not have PPI-responsive EoE based on esophageal biopsies performed after the patient has been on at least 8 weeks of high-dose PPI therapy (high-dose therapy refers to the total daily dose, which may have been administered as a once or twice daily dosing regimen). This may occur at the time of the qualifying esophagogastroduodenoscopy (EGD) (in which case the same proton pump inhibitor (PPI) regimen must be continued), or this may have been done previously (in which case PPI therapy may have been stopped if there was no response to therapy based on esophageal biopsy results). If PPI responsiveness was excluded by a previous EGD and biopsy, the historical EGD and biopsy must have been performed after the patient had been on a minimum of 6 weeks of high-dose PPI therapy.
• Participant will be on a stable (no changes) diet >=3 months prior to the screening visit (Visit -1).
• Participant is willing and able to continue any dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression) in effect at the screening visit (Visit -1). There should be no change to these regimens during study participation.
• All female participants must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) prior to enrollment into the study. Females of childbearing potential must agree to continue acceptable birth control measures (for example, abstinence, stable oral contraceptives, or double-barrier methods) throughout study participation.
• Participant is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.

Exclusion Criteria

• Participant has any condition or abnormality (including laboratory abnormalities), current or past, that, in the opinion of the principal investigator or medical monitor, would compromise the safety of the participant or interfere with or complicate the assessment of signs or symptoms of EoE. Such conditions may include psychiatric problems; neurologic deficits or disease; developmental delay; cardiovascular, metabolic, or pulmonary disease; or previous gastroesophageal surgery. These should be discussed with the medical monitor.
• Participant has used immunomodulatory therapy within 8 weeks prior to the qualifying EGD or between the qualifying EGD and baseline visit (Visit 1) or anticipates using immunomodulatory therapy during the treatment period (except for any ongoing regimen of allergy shots). Use of long-acting immunomodulatory therapy (for example, Rituxan) within 3 months of the qualifying EGD should be reviewed with the medical monitor.
• Participant has been using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates use during the treatment period; any temporary use (less than or equal to [<=]7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but cannot occur within 4 weeks of the final EGD.
• Participant has been on inhaled steroids and has not been on stable treatment for >=3 months prior to screening visit (Visit -1). Participants on inhaled steroids need to stay on a stable treatment during study participation. Participant has been on intranasal steroids and has not been on stable treatment for a minimum of 4 weeks prior to the qualifying EGD. After the qualifying EGD, participants with seasonal allergic rhinitis may resume (or discontinue) intranasal corticosteroids based on the participant's usual treatment regimen for allergy season.
• Participant has initiated, discontinued, or changed dosage regimen of PPIs, H2 antagonists, antacids, or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates changes in the use of such medications during the treatment period.
• Participant has been using cytochrome P450 3A4 (CYP450 3A4) inhibitors (for example, ketoconazole, grapefruit juice) within the 2 weeks prior to the baseline visit (Visit 1) or within 5 half-lives (whichever is greater) or anticipates using such medications during the treatment period.
• Participant has an appearance on qualifying EGD of an esophageal stricture (high-grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (for example, with an insertion tube diameter of greater than [>]9 millimeter [mm]).
• Participant is on a pure liquid diet or the 6-food elimination diet.
• Participant has had an esophageal dilation within the 3 months prior to screening (Visit -1).
• Participant has presence of esophageal varices at the screening endoscopy.
• Participant has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis; inflammatory bowel disease; or celiac disease.
• Participant has other diseases causing or associated with EoE, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.
• Participant has current evidence of oropharyngeal or esophageal candidiasis.
• Participant has a potentially serious acute or chronic viral infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, herpes esophagitis, or chicken pox/measles.
• Participant has upper gastrointestinal bleeding within 4 weeks prior to the screening visit (Visit - 1) or between the screening visit and baseline visit (Visit 1).
• Participant has evidence of active infection with Helicobacter pylori.
• Participant has evidence of unstable asthma within 4 weeks prior to the screening visit (Visit -1) and between the screening visit and baseline visit (Visit 1).
• Participant is female and pregnant or nursing.
• Participant has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids) or to any other ingredients of the investigational product.
• Participant has taken part and received intervention in an interventional study related to EoE (except for an interventional study for a topical swallowed steroid) within 6 months prior to the screening visit (Visit -1), or any investigational study within 30 days prior to the screening visit (Visit -1). An investigational topical swallowed steroid must have been discontinued at least 30 days prior to the screening visit (Visit -1).
• Participant has a history or high risk of noncompliance with treatment or regular clinic visits.
• Participant has previously completed, discontinued, or withdrawn from this study.
• Participant has participated in a previous clinical study involving oral budesonide suspension (OBS) (SHP621).
• Participant anticipates using sucralfate during the study.

• Minimum Eligible Age: 11 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Children's Hospital

Birmingham, Alabama, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Del Sol Research Management

Tucson, Arizona, United States

Adobe Clinical Research LLC

Tucson, Arizona, United States

Arkansas Gastroenterology

North Little Rock, Arkansas, United States

GW Research, Inc.

Chula Vista, California, United States

Rady Children's Hospital San Diego

San Diego, California, United States

Colorado Children's Hospital

Aurora, Colorado, United States

Asthma and Allergy Associates PC

Colorado Springs, Colorado, United States

Rocky Mountain Pediatric Gastroenterology

Lone Tree, Colorado, United States

Rocky Mountain Clinical Research LLC

Wheat Ridge, Colorado, United States

Connecticut Clinical Research Foundation

Bristol, Connecticut, United States

Connecticut GI, PC - Research Division

Farmington, Connecticut, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Nature Coast Clinical Research LLC

Inverness, Florida, United States

Borland Groover Clinic

Jacksonville, Florida, United States

Arnold Palmer Hospital For Children

Orlando, Florida, United States

Accord Clinical Research LLC

Port Orange, Florida, United States

Children's Center for Digestive Health Care

Atlanta, Georgia, United States

Gastroenterology Associates of Central Georgia, LLC

Macon, Georgia, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Grand Teton Research Group, PLLC

Idaho Falls, Idaho, United States

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Center for Children's Digestive Health

Park Ridge, Illinois, United States

University of Illinois College of Medicine at Peoria Pediatric Subspecialty Clinic

Peoria, Illinois, United States

OSF St Francis Medical Center

Peoria, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Gastroenterology of Southern Indiana

New Albany, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Cotton O'Neil Clinical Research Center

Topeka, Kansas, United States

Gastroenterology Associates LLC

Baton Rouge, Louisiana, United States

Clinical Trials Management LLC

Metairie, Louisiana, United States

Louisiana Research Center LLC

Shreveport, Louisiana, United States

Clinical Trials of America LA LLC - PPDS

West Monroe, Louisiana, United States

Tufts Medical Center

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Clinical Research Institute of Michigan

Chesterfield, Michigan, United States

West Michigan Clinical Research

Wyoming, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Minnesota Gastroenterology PA

Plymouth, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Bozeman Health Deaconess Hospital

Bozeman, Montana, United States

South Jersey Gastroenterology

Marlton, New Jersey, United States

Long Island Gastrointestinal Research Group LLP

Great Neck, New York, United States

Mount Sinai Hospital

New York, New York, United States

Asheville Gastroenterology Associates PA

Asheville, North Carolina, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Clinical Research of Charlotte

Charlotte, North Carolina, United States

Clinical Trials of America-NC, LLC - PPDS

Mount Airy, North Carolina, United States

Consultants For Clinical Research Inc

Cincinnati, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Gastrointestinal and Liver Diseases Consultants PC

Dayton, Ohio, United States

Great Lakes Gastroenterology

Mentor, Ohio, United States

Digestive Disease Specialists, Inc.

Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Greenville Hospital System

Greenville, South Carolina, United States

Greenville Hospital System

Greenville, South Carolina, United States

Gastro One

Germantown, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Houston Endoscopy and Research Center

Houston, Texas, United States

Digestive Health Center

Pasadena, Texas, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

Advanced Research Institute

Ogden, Utah, United States

Primary Children's Hospital, University of Utah

Salt Lake City, Utah, United States

Advanced Research Institute

Sandy City, Utah, United States

Emeritas Research Group

Lansdowne Town Center, Virginia, United States

Blue Ridge Medical Research

Lynchburg, Virginia, United States

Carilion Clinic

Roanoke, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Dellon ES, Collins MH, Katzka DA, Mukkada VA, Falk GW, Zhang W, Goodwin B, Terreri B, Boules M, Desai NK, Hirano I. Effect of randomized treatment withdrawal of budesonide oral suspension on clinically relevant efficacy outcomes in patients with eosinophilic esophagitis: a post hoc analysis. Therap Adv Gastroenterol. 2024 Dec 23;17:17562848241307602. doi: 10.1177/17562848241307602. eCollection 2024.

Reference Type: DERIVED

PMID: 39735351 (View on PubMed)

Hirano I, Collins MH, Katzka DA, Mukkada VA, Falk GW, Terreri B, Boules M, Zhang W, Desai NK, Dellon ES. Effect of Esophageal Dilation History on Efficacy Outcomes in Patients With Eosinophilic Esophagitis Receiving Budesonide Oral Suspension. Am J Gastroenterol. 2024 Nov 12;120(7):1502-1510. doi: 10.14309/ajg.0000000000003197.

Reference Type: DERIVED

PMID: 39631042 (View on PubMed)

Mukkada VA, Gupta SK, Gold BD, Dellon ES, Collins MH, Katzka DA, Falk GW, Williams J, Zhang W, Boules M, Hirano I, Desai NK. Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2023 Dec 1;77(6):760-768. doi: 10.1097/MPG.0000000000003948. Epub 2023 Sep 18.

Reference Type: DERIVED

PMID: 37718471 (View on PubMed)

Dellon ES, Collins MH, Katzka DA, Mukkada VA, Falk GW, Morey R, Goodwin B, Eisner JD, Lan L, Desai NK, Williams J, Hirano I; ORBIT2/SHP621-302 Investigators. Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1488-1498.e11. doi: 10.1016/j.cgh.2021.06.020. Epub 2021 Jun 26.

Reference Type: DERIVED

PMID: 34182150 (View on PubMed)

Hirano I, Collins MH, Katzka DA, Mukkada VA, Falk GW, Morey R, Desai NK, Lan L, Williams J, Dellon ES; ORBIT1/SHP621-301 Investigators. Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial. Clin Gastroenterol Hepatol. 2022 Mar;20(3):525-534.e10. doi: 10.1016/j.cgh.2021.04.022. Epub 2021 Apr 19.

Reference Type: DERIVED

PMID: 33887475 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SHP621-301

Identifier Type: -

Identifier Source: org_study_id