SHP621-302

Principal Investigator: Molly  O'Gorman
Keywords: Oral Budesonide Suspension , Eosinophilic Esophagitis Department: Pediatric Administration
IRB Number: 00093441 Co Investigator:  
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

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

Brief Summary

Currently there is no approved medication for the treatment of EoE. This Phase 3 study is being conducted to determine response to withdrawal of OBS, maintenance of response, extended therapy response, and response to intermittent therapy by evaluating both eosinophil counts and DSQ in adolescent and adults treated or withdrawn from OBS in this treatment extension study.

 Study Objectives Primary:

  • To evaluate the maintenance of efficacy over 36 weeks, as measured by the peak eosinophilic count and the Dysphagia Symptom Questionnaire (DSQ) score, through a randomized withdrawal design for subjects who responded to 12 weeks of OBS treatment (2 mg twice daily) with a peak count of ≤6 eosinophils (eos)/high-powered field (HPF) across all available esophageal levels at the final treatment visit and a ≥30% reduction in DSQ score from baseline during the SHP621-301 induction study

Key Secondary:

  • To evaluate the long-term treatment response over an extended period of 36 weeks for subjects who were randomized to OBS treatment but did not respond after 12 weeks in the SHP621-301 induction study (subject did not have a peak count of ≤6 eos/HPF across all available esophageal levels at the final treatment visit and/or a ≥30% reduction in DSQ score from baseline)

Secondary:

  • To evaluate the response to OBS treatment over 36 weeks for subjects who received placebo in the SHP621-301 induction study
  • To evaluate the effect of reinitiating OBS treatment for subjects who relapse after being randomized to placebo in the randomized withdrawal period (treatment-withdrawal-treatment reinitiation)
  • To assess endoscopically identified esophageal features as measured by the EoE Endoscopic Reference Score (EREFS)
  • To evaluate other response criteria based on histology and DSQ
  • To evaluate the long-term safety and tolerability of OBS treatment

Exploratory:

  • To assess the impact of OBS on the severity of dysphagia as measured by the Patient Global Impression of Severity (PGI-S)
  • assess quality of life (QoL) for subjects as measured by patient reported outcomes, Adult EoE-QoL (EoE-QoL-A), EuroQol-5 Dimensions (EQ-5D) and Pediatric Quality of Life Inventory – EoE (PedsQL-EoE

Inclusion 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 (including DSQ compliance and restrictions defined in this protocol.

 

Exclusion Criteria

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, 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 is expected to respond to treatment.
  13. Subject has a potentially serious 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.