Clinical trial NCT02736409: An Extension Study to Evaluate Maintenance of Efficacy and Long-term Treatment Effect of Oral Budesonide Suspension (OBS) in Adults and Adolescents With Eosinophilic Esophagitis (EoE)
Official title: A Phase 3, Multicenter, Double-blind Extension Study to Evaluate Maintenance of Efficacy of Oral Budesonide Suspension (OBS) and Long-term Treatment Effect of OBS in Adolescent and Adult Subjects (11 to 55 Years of Age, Inclusive) With Eosinophilic Esophagitis (EoE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Esophagitis (EoE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-04-13
Enrollment: 219
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: This is a multicenter, double- blind extension study of Oral Budesonide Suspension (OBS) in adults and adolescents (11 to 55 years of age, inclusive) with Eosinophilic Esophagitis (EoE) who have completed participation in the SHP621-301 induction study (NCT02605837). The primary objective is to evaluate the maintenance of efficacy of OBS over 36 weeks. Maintenance of efficacy will be measured by the peak eosinophilic count and Dysphagia Symptom Questionnaire (DSQ) score.


Eligibility criteria: Inclusion Criteria:

1. Subject completed SHP621-301 induction study.
2. Subject is able to provide written informed consent (subject, parent or legal guardian and, as appropriate, subject assent) to participate in the study before completing any study-related procedures.
3. Subject is male or female aged 11-55 years, inclusive, at time of consent for SHP621-301 study.
4. Subject is willing and able to continue any dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression; see exclusions below) in effect at the screening visit (Visit 0). There should be no changes to these regimens during study participation.
5. All female subjects 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 (eg, abstinence, stable oral contraceptives, or double-barrier methods) throughout study participation and for 30 days following the last dose of investigational product.
6. Subject is willing and has an understanding and ability to fully comply with study procedures including DSQ compliance (completed the DSQ on ≥70% of days in any 2 consecutive weeks of the screening period)and restrictions defined in this protocol

Exclusion Criteria:

1. Subject has changes in medications that could affect the study or diet in the weeks since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.
2. Subject using immunomodulatory therapy since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of immunomodulatory therapy during the treatment period (except for any ongoing regimen of allergy shots); any temporary use (≤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 scheduled EGDs.
3. Subject using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use during the treatment period; any temporary use (≤7 days) or initiation of new steroid treatment during the study should be documented and discussed with medical monitor prospectively but cannot occur within the 4 weeks of the scheduled EGDs.
4. Subject on inhaled or intranasal steroids and not on a stable dose between the baseline visit (Visit 1) of the SHP621-301 study and the screening EGD of this study.
5. Subject has initiated, discontinued, or changed dosage regimen of proton pump inhibitors (PPIs), H2 antagonists, antacids, antihistamines, or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated changes in the use of such medications during the treatment period.
6. Subject using Cytochrome P450 3A4 inhibitors (eg, ketoconazole, grapefruit juice) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of such medications during the treatment period.
7. Subject has an appearance on screening 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 (eg, with an insertion tube diameter of \>9mm).
8. Subject is on a pure liquid diet or the six-food elimination diet.
9. Subject has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study.
10. Subject has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis, inflammatory bowel disease, or celiac disease.
11. Subject has other diseases causing or associated with esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.
12. Subject has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment.

    Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study is not an exclusion as long as the subject received treatment for candidiasis and is expected to respond to treatment.
13. Subject has acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles.
14. Subject has upper gastrointestinal bleeding identified in the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.
15. Subject has evidence of active infection with Helicobacter pylori.
16. Subject has evidence of unstable asthma since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.
17. Subject is female and pregnant or nursing.
18. Subject has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids), or to any other ingredients of the study medication.
19. Subject has a history or high risk of noncompliance with treatment or regular clinic visits.
20. Subject is on sucralfate or anticipates using sucralfate during the treatment period.

Primary outcomes:
measure: Proportion of Participants Who Had Relapse During the Entire Week 36 Period
timeFrame: Week 36
Secondary outcomes:
measure: Proportion of Participants With Long-term Treatment Response From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Week 36
measure: Proportion of Participants With Long-term Treatment Response From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Week 36
measure: Proportion of Participants Who Had a Histologic Response (Eosinophil Count of Less Than or Equal to (<or=6)/High-Powered Field [HPF]) at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36
timeFrame: Baseline of SHP621-301 (NCT02605837), Week 12 and Week 36
measure: Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
measure: Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Total Endoscopy Score at Week 12 and Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
measure: Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Total Endoscopy Score at Week 12 and Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
measure: Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
measure: Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count at Week 12 and Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
measure: Proportion of Participants Who Had Peak Eosinophil Count Less Than (<) 15/High-Powered Field (HPF) at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had Peak Eosinophil Count Less Than or Equal to (< or =) 1/High-Powered Field (HPF) at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
measure: Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
measure: Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 an Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
measure: Change From Current Study (SHP621-302 [NCT02736409]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 and Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
measure: Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
measure: Percent Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Percent Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
measure: Proportion of Participants Who Had Overall Binary Response I From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 of Current Study
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had Overall Binary Response I From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had Overall Binary Response II From Induction Study SHP621-301 (NCT02605837) Baseline at Week 12 and Week 36 of Current Study
timeFrame: Week 12 and Week 36
measure: Proportion of Participants Who Had Overall Binary Response II From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36
timeFrame: Week 12 and Week 36
measure: Change in the DSQ + Pain Score (Questions 2+3+4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Change in the DSQ+ Pain Score (Questions 2+3+4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
measure: Change in the DSQ Pain Score (Question 4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Change in the DSQ Pain Score (Question 4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE's)
timeFrame: From start of the study drug administration up to follow up (Week 40)
measure: Change in DXA (Dual-Energy X-ray Absorptiometry) Imaging Results (Location: Lumbar Spine [L1-L4]) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Change in DXA Imaging Results (Location: Lumbar Spine [L1-L4]) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
measure: Change in DXA Imaging Results (Location: Whole Body) From Baseline of Induction Study (SHP621-301 [NCT02605837]) at Week 36 of Current Study
timeFrame: Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
measure: Change in DXA Imaging Results (Location: Whole Body) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36
timeFrame: Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
Other outcomes:
measure: Proportion of Participants Who Had a Histologic Response (Eosinophil Count of Greater Than or Equal to (>or=15)/High-Powered Field [HPF]) Before or at Week 12 and Before or at Week 36
timeFrame: Week 12 and Week 36
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: 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: Orlando
country: United States
facility: Arnold Palmer Hospital For Children
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: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: University of Illinois College of Medicine at Peoria Pediatric Subspecialty Clinic
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Albany
country: United States
facility: Aquiant Research
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: 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: 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: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group LLP
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
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: 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: 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: 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: Salt Lake City
country: United States
facility: Primary Children's Hospital
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
Study officials:
affiliation: Shire
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.