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)

Shire62 sites in 1 country219 target enrollmentApril 1, 2016

ConditionsEosinophilic Esophagitis (EoE)

InterventionsOral Budesonide Suspension (OBS)Placebo

DrugsOral Budesonide Suspension (OBS)Placebo

Overview

Phase: Phase 3
Intervention: Oral Budesonide Suspension (OBS)
Conditions: Eosinophilic Esophagitis (EoE)
Sponsor: Shire
Enrollment: 219
Locations: 62
Primary Endpoint: Proportion of Participants Who Had Relapse During the Entire Week 36 Period
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 1, 2016

End Date

November 12, 2019

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Shire

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject completed SHP621-301 induction study.
•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.
•Subject is male or female aged 11-55 years, inclusive, at time of consent for SHP621-301 study.
•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.
•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.
•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

•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.
•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.
•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.
•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.
•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.
•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.
•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).
•Subject is on a pure liquid diet or the six-food elimination diet.
•Subject has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study.
•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.

Arms & Interventions

Arms A OBS Completers/ Responders

Arm A Oral Budesonide Suspension Completers/ Responders

Intervention: Oral Budesonide Suspension (OBS)

Arm B OBS Completers/ Responders

Arm B Oral Budesonide Suspension Completers/ Responders. 1:1 randomization for Arms A and B

Intervention: Placebo

Arm C OBS Completers/ Non-Responders

Arm C Oral Budesonide Suspension Completers/ Non-Responders

Intervention: Oral Budesonide Suspension (OBS)

Arm D Placebo Completers

Intervention: Oral Budesonide Suspension (OBS)

Outcomes

Primary Outcomes

Proportion of Participants Who Had Relapse During the Entire Week 36 Period

Time Frame: Week 36

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.

Secondary Outcomes

Proportion of Participants With Long-term Treatment Response From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study(Week 36)
Proportion of Participants With Long-term Treatment Response From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36)
Number of Participants With Treatment Emergent Adverse Events (TEAE's)(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(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(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(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(Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36)