SHP621-301

Principal Investigator: Molly  O'Gorman
Keywords: esophageal dysfunction , dysphagia Department: Pediatric Administration
IRB Number: 00088371 Co Investigator:  
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Amy Holman
amy.holman@hsc.utah.edu
801-587-7484

Brief Summary

Study Purpose:
Currently there is no approved medication for the treatment of EoE. This study is being conducted in order to provide safety and efficacy data demonstrating histologic response (as measured by eosinophilic count ≤6/HPF) and improvement in dysphagia symptoms (as measured by the DSQ) following 12 weeks of treatment with OBS in adolescent and adult subjects with EoE.
 
Study Objectives
 

Primary Objectives

The co-primary objectives of the study are to demonstrate in a placebo-controlled trial that:
  • OBS induces a histologic response (eosinophilic count ≤6/HPF) in adolescent and adult subjects with EoE over a 12-week course of therapy.
  • OBS reduces dysphagia, as measured by the DSQ, by at least 30% from baseline in adolescent and adult subjects with EoE over a 12-week course of therapy.

Secondary Objectives

The key secondary objective of this study is:
  • OBS reduces dysphagia, as measured by the DSQ score from baseline to the final treatment period evaluation (Visit 4).
Additional secondary objectives of the study are:
  • To assess the response of endoscopically identified esophageal features to OBS as compared to placebo as measured by the EoE Endoscopic Reference Score (EREFS)
  • To explore other responding criteria based on histology and DSQ
  • To assess the impact of OBS on pain, as measured by the DSQ
  • To evaluate the safety and tolerability of OBS over a 12-week course of therapy
  • To obtain OBS pharmacokinetic data in adult subjects with EoE
Exploratory Objective
The exploratory objective of this study is:
  • To assess the impact of OBS on the severity of dysphagia as measured by the Patient Global Impression of Severity (PGI-S)

Inclusion Criteria

1. 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.
 
2. Subject is male or female aged 11-55 years, inclusive, at time of consent.
 
3. Subject has histologic evidence of EoE with a peak eosinophil count of ≥15/HPF, from 2 of 3 (proximal, mid-, and/or distal) levels of the esophagus at the screening endoscopy.
 
4. Subject has a history of clinical symptoms of esophageal dysfunction (eg, eating problems, abdominal pain, heartburn, dysphagia, vomiting, food impaction, weight loss) intermittently or continuously at screening (Visit -1).
 
5. Subject must have experienced dysphagia (response of “yes” to question 2 on DSQ) on a minimum of 4 days and completed the DSQ on ≥70% of days in any 2 consecutive weeks of the screening period and in the last 2 weeks prior to the baseline visit (Visit 1).
 
6. Subject must not have PPI-responsive EoE based on esophageal biopsies performed after the patient has been on at least 8 weeks of high-dose PPI therapy (high-dose therapy refers to the total daily dose, which may have been administered as a once- or twice daily dosing regimen). This may occur at the time of the qualifying EGD (in which case the same PPI regimen must be continued), or this may have been done previously (in which case PPI therapy may have been stopped if there was no response to therapy based on esophageal biopsy results). If PPI responsiveness was excluded by a previous EGD and biopsy, the historical EGD and biopsy must have been performed after the patient had been on a minimum of 6 weeks of high-dose PPI therapy.

7. Subject will be on a stable (no changes) diet ≥3 months prior to the screening visit (Visit -1).

8. 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 -1). There should be no change to these regimens during study participation.
 
9. 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.
 
10. Subject is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.

Exclusion Criteria

1. Subject has any condition or abnormality (including laboratory abnormalities), current or past, that, in the opinion of the principal investigator or medical monitor, would compromise the safety of the subject or interfere with or complicate the assessment of signs or symptoms of EoE. Such conditions may include psychiatric problems; neurologic deficits or disease; developmental delay; cardiovascular, metabolic, or pulmonary disease; or previous gastroesophageal surgery. These should be discussed with the medical monitor.
 
2. Subject has used immunomodulatory therapy within 8 weeks prior to the qualifying EGD or between the qualifying EGD and baseline visit (Visit 1) or anticipates using immunomodulatory therapy during the treatment period (except for any ongoing regimen of injected or sublingual maintenance immunotherapy for allergies). Use of long-acting immunomodulatory therapy (eg, Rituxan) within 3 months of the qualifying EGD should be reviewed with the medical monitor.
 
3. Subject has been using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates use during the treatment period; any temporary use 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 the final EGD.
 
4. Subject has been on inhaled steroids and has not been on stable treatment for ≥3 months prior to screening visit (Visit -1). Subjects on inhaled steroids need to stay on a stable treatment during study participation.  Subject has been on intranasal steroids and has not been on stable treatment for a minimum of 4 weeks prior to the qualifying EGD. After the qualifying EGD, subjects with seasonal allergic rhinitis may resume (or discontinue) intranasal corticosteroids based on the subject's usual treatment
regimen for allergy season.
 
5. Subject has initiated, discontinued, or changed dosage regimen of PPIs, H2 antagonists, antacids or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) within the 4 weeks prior to the qualifying EGD, between the qualifying esophagogastroduodenoscopy (EGD) and baseline visit (Visit 1), or anticipates changes in the use of such medications during the treatment period.
 
6. Subject has been using cytochrome P450 3A4 (CYP450 3A4) inhibitors (eg, ketoconazole, grapefruit juice) within the 2 weeks prior to the baseline visit (Visit 1) or within 5 half-lives (whichever is greater) or anticipates using such medications during the treatment period.
 
7. Subject has an appearance on qualifying 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 >9 mm).
 
8. Subject is on a pure liquid diet or the 6-food elimination diet.
 
9. Subject has had an esophageal dilation within the 3 months prior to screening (Visit -1).
 
10. Subject has presence of esophageal varices at the screening endoscopy.
 
11. 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.
 
12. Subject has other diseases causing or associated with EoE, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.
 
13. Subject has current evidence of oropharyngeal or esophageal candidiasis.
 
14. Subject has a potentially serious acute or chronic viral infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, herpes esophagitis, or chicken pox/measles.
 
15. Subject has upper gastrointestinal bleeding within 4 weeks prior to the screening visit (Visit -1) or between the screening visit and baseline visit (Visit 1).
 
16. Subject has evidence of active infection with Helicobacter pylori.
 
17. Subject has evidence of unstable asthma within 4 weeks prior to the screening visit (Visit -1) and between the screening visit and baseline visit (Visit 1).
 
18. Subject is female and pregnant or nursing.
 
19. Subject has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids) or to any other ingredients of the investigational product.
 
20. Subject has taken part and received intervention, other than another topical corticosteroid, in an interventional study related to EoE within 6 months prior to the screening visit (Visit -1), and/or investigational study within 30 days prior to the screening
visit (Visit -1).
 
21. Subject has a history or high risk of noncompliance with treatment or regular clinic visits
 
22. Subject has previously completed, discontinued, or withdrawn from this study.
 
23. Subject has participated in a previous clinical study involving OBS (SHP621).
 
24. Subject anticipates using sucralfate during the study.