Clinical trial NCT02605837: A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved
Official title: Oral Budesonide Suspension (OBS) in Adolescent and Adult Subjects (11 to 55 Years of Age, Inclusive) With Eosinophilic Esophagitis: A Phase 3 Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Esophagitis (EoE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-11-16
Enrollment: 318
Sex: ALL
Minimum age (years): 11
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Histologic Response at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
measure: Number of Participants With Dysphagia Symptom Response at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
Secondary outcomes:
measure: Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Combined Score at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Total Endoscopy Score at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
measure: Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Histopathologic Epithelial Features Combined Total Score Ratio (TSR) at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Number of Participants With Dysphagia Symptom Response (Binary Response) at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
measure: Number of Participants With Overall Binary Response I at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
measure: Number of Participants With Overall Binary Response II at the Final Treatment Period Evaluation (Week 16)
timeFrame: Week 16
measure: Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) + Pain Score (Questions 2 +3+4) at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) Pain Score (Question 4) at the Final Treatment Period Evaluation (Week 16)
timeFrame: Baseline, Week 16
measure: Number of Participants With Treatment-Emergent Adverse Events (AE)
timeFrame: From start of study drug administration up to follow-up (Week 20)
measure: Area Under the Plasma Concentration-Time Curve (AUCtau) Between the Defined Interval of Budesonide Doses
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Maximum Observed Concentration (Cmax) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Terminal Rate Constant (Lambda Z) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Terminal Half-Life (t1/2) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Apparent Oral Clearance (CL/F) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
measure: Apparent Volume of Distribution (Vz/F) of Budesonide in Plasma
timeFrame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research LLC
state: Arizona
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Chula Vista
country: United States
facility: GW Research, Inc.
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Aurora
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates PC
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Pediatric Gastroenterology
state: Colorado
city: Wheat Ridge
country: United States
facility: Rocky Mountain Clinical Research LLC
state: Colorado
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation
state: Connecticut
city: Farmington
country: United States
facility: Connecticut GI, PC - Research Division
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Inverness
country: United States
facility: Nature Coast Clinical Research LLC
state: Florida
city: Jacksonville
country: United States
facility: Borland Groover Clinic
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital For Children
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research LLC
state: Florida
city: Atlanta
country: United States
facility: Children's Center for Digestive Health Care
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia, LLC
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Park Ridge
country: United States
facility: Center for Children's Digestive Health
state: Illinois
city: Peoria
country: United States
facility: University of Illinois College of Medicine at Peoria Pediatric Subspecialty Clinic
state: Illinois
city: Peoria
country: United States
facility: OSF St Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Albany
country: United States
facility: Gastroenterology of Southern Indiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center
state: Kansas
city: Baton Rouge
country: United States
facility: Gastroenterology Associates LLC
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center LLC
state: Louisiana
city: West Monroe
country: United States
facility: Clinical Trials of America LA LLC - PPDS
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan
state: Michigan
city: Wyoming
country: United States
facility: West Michigan Clinical Research
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Plymouth
country: United States
facility: Minnesota Gastroenterology PA
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Marlton
country: United States
facility: South Jersey Gastroenterology
state: New Jersey
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group LLP
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates PA
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
city: Mount Airy
country: United States
facility: Clinical Trials of America-NC, LLC - PPDS
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants For Clinical Research Inc
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dayton
country: United States
facility: Gastrointestinal and Liver Diseases Consultants PC
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology
state: Ohio
city: Oklahoma City
country: United States
facility: Digestive Disease Specialists, Inc.
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Endoscopy and Research Center
state: Texas
city: Pasadena
country: United States
facility: Digestive Health Center
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Salt Lake City
country: United States
facility: Primary Children's Hospital, University of Utah
state: Utah
city: Sandy
country: United States
facility: Advanced Research Institute
state: Utah
city: Lansdowne Town Center
country: United States
facility: Emeritas Research Group
state: Virginia
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.