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)

• ClinicalTrials.gov Identifier: NCT02736409
• Recruitment Status: Active, not recruiting
• First Posted: April 13, 2016
• Last Update Posted: April 23, 2019
• Sponsor: Shire
• Information provided by (Responsible Party): Shire

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Eosinophilic Esophagitis (EoE)	Drug: Oral Budesonide Suspension (OBS); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 29, 2016
• Estimated Primary Completion Date: November 22, 2019
• Estimated Study Completion Date: November 22, 2019

Arms and Interventions

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; Arm D Placebo Completers	Drug: Oral Budesonide Suspension (OBS); OBS 2mg twice daily

Outcome Measures

Primary Outcome Measures :

1. Efficacy of SHP621 as measured by peak esophangeal eosinophil count [ Time Frame: 36 weeks ]
2. Efficacy of SHP621 measured by the Dysphagia Symptom Questionnaire (DSQ) score [ Time Frame: 36 weeks ]

Secondary Outcome Measures :

1. Participant long-term treatment response measured by peak eosinophil count from baseline to 36 weeks for subjects who were randomized to OBS treatment but did not respond after 16 weeks in SHP621-301 induction study [ Time Frame: 36 weeks ]
2. Participant response to OBS treatment over 36 weeks as meaured by reduction in DSQ score for subjects who received placebo in the SHP621-301 induction study [ Time Frame: 36 weeks ]
3. Participant response to reinitiating OBS treatment as measured by change in total endoscopy score for subjects who relapse after being randomized to placebo in the randomized withdrawal period [ Time Frame: 36 weeks ]
4. Participant response as assessed by endoscopically identified esophageal features as measured by the EoE Endoscopic Reference Score (EREFS) [ Time Frame: 36 weeks ]
5. Number of participants with adverse events by MedDRA preferred term as a measure of safety and tolerability [ Time Frame: 40 weeks ]
6. Participant long-term treatment response measured by reduction in DSQ combined score from baseline to 36 weeks for subjects who were randomized to OBS treatment but did not respond after 16 weeks in SHP621-301 induction study [ Time Frame: 36 weeks ]
7. Participant response to OBS treatment over 36 weeks as meaured by peak eosinophil count for subjects who received placebo in the SHP621-301 induction study [ Time Frame: 36 weeks ]
8. Participant response to OBS treatment over 36 weeks as meaured by change in total endoscopy score for subjects who received placebo in the SHP621-301 induction study [ Time Frame: 36 weeks ]
9. Participant response to reinitiating OBS treatment as measured by change in EREFS for subjects who relapse after being randomized to placebo in the randomized withdrawal period [ Time Frame: 36 weeks ]

Eligibility Criteria

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

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.

Contacts and Locations

  Show 62 Study Locations

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Shire

More Information

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02736409 History of Changes
• Other Study ID Numbers: SHP621-302
• First Posted: April 13, 2016
• Last Update Posted: April 23, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. 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.
• URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

Additional relevant MeSH terms:

Esophagitis; Eosinophilic Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Budesonide; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists