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) (ORBIT2)

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)

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.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis (EoE)
• Intervention / Treatment: Drug: Oral Budesonide Suspension (OBS); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research LLC
    • Tucson, Arizona, United States, 85710
      • Del Sol Research Management
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Chula Vista, California, United States, 91910
      • GW Research, Inc.
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Children's Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates PC
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Pediatric Gastroenterology
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Foundation
    • Farmington, Connecticut, United States, 06032
      • Connecticut GI, PC - Research Division
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Florida
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research LLC
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Hospital for Children
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Center for Digestive Health Care
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia, LLC
  • Idaho
    • Idaho Falls, Idaho, United States
      • Grand Teton Research Group, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Peoria, Illinois, United States, 61603
      • University of Illinois College of Medicine at Peoria Pediatric Subspecialty Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • New Albany, Indiana, United States, 47150
      • Gastroenterology of Southern Indiana
    • New Albany, Indiana, United States, 47150
      • Aquiant Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates LLC
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management LLC
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center LLC
    • West Monroe, Louisiana, United States, 71291
      • Clinical Trials of America LA LLC - PPDS
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology PA
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Montana
    • Bozeman, Montana, United States, 59718
      • Bozeman Health Deaconess Hospital
  • New York
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group LLP
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates PA
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina At Chapel Hill
    • Charlotte, North Carolina, United States, 28277
      • Clinical Research of Charlotte
    • Mount Airy, North Carolina, United States, 27030
      • Clinical Trials of America-NC, LLC - PPDS
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • Consultants For Clinical Research Inc
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Dayton, Ohio, United States, 45415
      • Gastrointestinal and Liver Diseases Consultants PC
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Hospital System
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • San Antonio Military Medical Center
    • Houston, Texas, United States, 77079
      • Houston Endoscopy and Research Center
    • Pasadena, Texas, United States, 77505
      • Digestive Health Center
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
    • Sandy, Utah, United States, 84092
      • Advanced Research Institute
  • Virginia
    • Lansdowne Town Center, Virginia, United States, 20176
      • Emeritas Research Group
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research
    • Roanoke, Virginia, United States, 24013
      • Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arms A OBS Completers/ Responders; Arm A Oral Budesonide Suspension Completers/ Responders	Drug: Oral Budesonide Suspension (OBS); OBS 2mg twice daily
Placebo Comparator: Arm B OBS Completers/ Responders; Arm B Oral Budesonide Suspension Completers/ Responders. 1:1 randomization for Arms A and B	Drug: Placebo; Matching Placebo dose
Experimental: Arm C OBS Completers/ Non-Responders; Arm C Oral Budesonide Suspension Completers/ Non-Responders	Drug: Oral Budesonide Suspension (OBS); OBS 2mg twice daily
Experimental: Arm D Placebo Completers	Drug: Oral Budesonide Suspension (OBS); OBS 2mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Had Relapse During the Entire Week 36 Period	Relapse (Yes/No) was defined as meeting both the eosinophil histology relapse criterion and the dysphagia symptom relapse criterion. Eosinophil histology relapse was defined as an eosinophil count of greater than or equal to(> or =) 15 per high-power field (eos/hpf) from at least 2 of 3 levels of the esophagus. Dysphagia symptom relapse was defined as having at least 4 days of dysphagia (with answer 'Yes' for question 2 in DSQ [Dysphagia Symptom Questionnaire]) in the 2-week period prior to the scheduled visit, as determined by the DSQ.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Long-term Treatment Response From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study	Long-term response from SHP621-301 baseline defined: histologic response,defined as peak eosinophil count of less than or equal to(< or =)6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score(Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(didyoueatsolid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84.Highervaluesrepresentingworseoutcome.Negative change from baseline indicates symptoms decreased.	Week 36
Proportion of Participants With Long-term Treatment Response From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	Long-term response from baseline defined: histologic response, defined as peak eosinophil count of less than or equal to(< or =) 6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score (Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(did you eat solid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84. Higher values representing worse outcome.Negative change from baseline indicates symptoms decreased.	Week 36
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	Histology response was defined as a peak eosinophil count of <or=6/HPF across all available levels at Week 12 and Week 36.	Week 12 and Week 36
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	Dysphagia symptom response with respect to the baseline of induction study (SHP621-301 [NCT02605837]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 of current study from baseline of the induction study. DSQ contain 4 questions, all participants used a diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was No, then diary ended for that day. If participant answered Yes,he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing worse outcome. Negative change from baseline indicates symptoms decreased.	Baseline of SHP621-301 (NCT02605837), Week 12 and Week 36
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	Dysphagia symptom response with respect to the baseline of current study (SHP621-302 [NCT02736409]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 from baseline of the current study. DSQ contain 4 questions, all participants used diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was "No", then diary ended for that day. If participant answered "Yes",he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q 3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Total Endoscopy Score at Week 12 and Week 36 of Current Study	Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Total Endoscopy Score at Week 12 and Week 36	Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 of Current Study	Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count at Week 12 and Week 36 of current study was reported.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count at Week 12 and Week 36	Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count at Week 12 and Week 36 was reported.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
Proportion of Participants Who Had Peak Eosinophil Count Less Than (<) 15/High-Powered Field (HPF) at Week 12 and Week 36	Proportion of participants who had Peak Eosinophil Count less than (<) 15/HPF at Week 12 and Week 36 were reported.	Week 12 and Week 36
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	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 were reported.	Week 12 and Week 36
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	Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 of current study were reported.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
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	Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 were reported.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
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	Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36
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	Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36
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	Dysphagia symptom response from the baseline of SHP621-301, was defined as >or=50% reduction in DSQ combined score (questions [Q] 2+3) from baseline of the induction study at Week 12 and 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1(did you eat solid food) and Q2(didfood passslowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3(did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. Anegative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
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	Dysphagia symptom response from the baseline of SHP621-302, was defined as >or=50% reduction in DSQ combined score (questions 2+3) from baseline of the induction study at Week 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1 (did you eat solid food) and Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study	DSQ contain 4 questions (Q), all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	DSQ contain 4 questions, all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. Change in DSQ combined score (Questions 2+3) from baseline of current study at Week 36 was reported.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
Percent Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study	Percent change in DSQ combined score from Induction Study (SHP621-301 [NCT02605837]) baseline to current study (SHP621-302 [NCT02736409]) final treatment period (Week 36) was reported.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Percent Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	Percent change in DSQ combined score from baseline to final treatment period (Week 36) of current study was reported.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
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	Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline of the induction study (SHP621-301 [NCT02605837]) at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
Proportion of Participants Who Had Overall Binary Response I From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36	Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
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	Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 50% reduction in DSQ combined score from baseline of the SHP621-301 study at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
Proportion of Participants Who Had Overall Binary Response II From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36	Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Week 12 and Week 36
Change in the DSQ + Pain Score (Questions 2+3+4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study	DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= ([sum of points from questions 2+3+4 in the daily DSQ] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Change in the DSQ+ Pain Score (Questions 2+3+4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	DSQ contained 4 questions, all participants used a diary, and responded to Questions (Q) 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Q2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to Questions 2, 3, and 4. Question 1 was excluded from the DSQ + pain score. DSQ + pain score=(Sum of points from questions 2+3+4 in the daily DSQ)*14 Days/Number of dairies reported with non-missing data. Scale range was 0 - 2 for Q2, 0 - 4 for Q3 and 0 - 4 for Q4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
Change in the DSQ Pain Score (Question 4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study	DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Change in the DSQ Pain Score (Question 4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
Number of Participants With Treatment Emergent Adverse Events (TEAE's)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or deteriorated on or after the date of the first dose of double-blind IP in SHP621-302 and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact.	From start of the study drug administration up to follow up (Week 40)
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	The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Change in DXA Imaging Results (Location: Lumbar Spine [L1-L4]) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36
Change in DXA Imaging Results (Location: Whole Body) From Baseline of Induction Study (SHP621-301 [NCT02605837]) at Week 36 of Current Study	The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline of induction study (SHP621-301 [NCT02605837]), Week 36
Change in DXA Imaging Results (Location: Whole Body) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36	The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.	Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Eosinophil histology relapse was defined as an eosinophil count of >or=15 eos/HPF from at least 2 of 3 levels of the esophagus.	Week 12 and Week 36

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): November 12, 2019
• Study Completion (Actual): November 12, 2019

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: April 7, 2016
• First Posted (Estimate): April 13, 2016

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: SHP621-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)