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)

Shire

Status and phase: Completed; Phase 3

Conditions: Eosinophilic Esophagitis (EoE)

Treatments: Drug: Placebo; Drug: Oral Budesonide Suspension (OBS)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02736409

SHP621-302

Details and patient eligibility

About

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.

Enrollment: 219 patients

Sex: All

Ages: 11 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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219 participants in 4 patient groups, including a placebo group

Arms A OBS Completers/ Responders

Experimental group

Description:

Arm A Oral Budesonide Suspension Completers/ Responders

Treatment:

Drug: Oral Budesonide Suspension (OBS)

Arm B OBS Completers/ Responders

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Arm C OBS Completers/ Non-Responders

Experimental group

Description:

Arm C Oral Budesonide Suspension Completers/ Non-Responders

Treatment:

Drug: Oral Budesonide Suspension (OBS)

Arm D Placebo Completers

Experimental group

Description:

Arm D Placebo Completers

Treatment:

Drug: Oral Budesonide Suspension (OBS)