Oral Viscous Budesonide Suspension (MB-7) in Subjects With Eosinophilic Esophagitis: A Randomized, Placebo-Controlled, Dose-Ranging Study in Children and Adolescents
Overview
- Phase
- Phase 2
- Intervention
- placebo
- Conditions
- Eosinophilic Esophagitis (EoE)
- Sponsor
- Shire
- Enrollment
- 82
- Locations
- 20
- Primary Endpoint
- Percent of Participants Who Responded to Therapy
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a randomized, placebo-controlled, parallel-arm, dose-ranging study in subjects with eosinophilic esophagitis, 2-18 years of age. Eligible subjects will be randomized into one of four treatment groups. The Treatment Period will be 12 weeks during which subjects will visit the clinic at study weeks 0 (Baseline Visit), 2, 4, 8 and 12 (Final Treatment Evaluation) for clinical symptom assessment and safety evaluation (including adverse events and vital signs). All study treatments (active drug and placebo) will be administered orally twice daily during the Treatment Period, once in the morning after breakfast and once in the evening at bedtime.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female subjects between the ages of 2-18 years, inclusive
- •History of clinical symptoms of esophageal dysfunction intermittently or continuously
- •Histologic evidence of EoE with a peak eosinophil count of greater than or equal to 20 eosinophils per HPF, from two or more levels of the esophagus, within six weeks prior to the Baseline Visit
- •At the Baseline Visit, subjects must have symptoms with a total EoE Clinical Symptom Score of greater than or equal to 3
- •Willingness and ability to continue the dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression, if any) in effect at the Screening Visit
- •Females of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin) prior to randomization into the study and sexually active subjects must agree to continue acceptable birth control measures throughout the duration of the study
- •Written informed consent (parent or legal guardian) and, as appropriate, subject assent
Exclusion Criteria
- •Current use of immunomodulatory therapy (or anticipated use within 12 weeks following the Baseline Visit)
- •Diagnosis of inflammatory bowel disease
- •Chronic viral infection or immunodeficiency condition (current)
- •Use of swallowed topical corticosteroids for EoE in the 1 month prior to the biopsy required for entrance to this study or at any time between the biopsy and the Baseline Visit
- •Use of systemic (oral or parenteral) corticosteroid within 1 month prior to the biopsy required for entrance to this study or at any time between the biopsy and the Baseline Visit
- •Morning plasma cortisol level below the lower limit of normal (per Central Laboratory reference range) at the Screening Visit
- •Upper gastrointestinal bleeding within 1 month prior to the Screening Visit or between the Screening Visit and Baseline Visit
- •Current use of anticoagulants
- •Current disease of the gastrointestinal tract aside from the current EoE diagnosis
- •Evidence of concurrent eosinophilic gastritis, enteritis, colitis, or proctitis
Arms & Interventions
1
Intervention: placebo
2
Low Dose Group
Intervention: budesonide
3
Medium Dose Group
Intervention: budesonide
4
High Dose Group
Intervention: budesonide
Outcomes
Primary Outcomes
Percent of Participants Who Responded to Therapy
Time Frame: 12 weeks after the start of treatment
Response was defined as a ≥50% reduction from baseline in the eosinophilic esophagitis (EoE) clinical symptom score (CSS) and a reduction in peak eosinophil count to ≤6/high power field (light microscopy) from esophageal biopsies collected at the final evaluation. The EoE CSS, scored from 0 to 18 by a doctor, assessed 6 categories: 1) heartburn, 2) abdominal pain, 3) nocturnal awakening with symptoms, 4) nausea, regurgitation, or vomiting, 5) anorexia or early satiety, and 6) dysphagia, odynophagia, or food impaction (a severe symptom). Each domain was scored as follows, based on symptoms in the 2 weeks prior to the assessment: 0 = No symptoms and no coping behaviors required; 1 = Mild: Symptoms limited to 1-3 days or no symptoms because coping behaviors were required to avoid symptoms; 2 = Moderate: Symptoms on \>3 days, with or without minor coping behaviors; 3 = Severe: Symptoms interfered with activities of daily living or symptoms persisted and required major coping behaviors.
Secondary Outcomes
- Percent of Participants With Histologic Response(12 weeks after the start of treatment)
- Percent of Participants With Histologic Remission(12 weeks after the start of treatment)
- Percent Change From Baseline in Peak Eosinophil Count(Baseline, 12 weeks after the start of treatment)
- Percent Change From Baseline in Eosinophilic Esophagitis (EoE) Clinical Symptom Score (CSS)(Baseline, 12 weeks after the start of treatment)
- Change From Baseline in Endoscopy Score(Baseline, 12 weeks after the start of treatment)
- Percent of Participants With Clinical Remission(12 weeks after the start of treatment)
- Percent of Participants With Clinical Response(12 weeks after the start of treatment)
- Time to Maximum (Tmax) And Half Maximum (T1/2) Plasma Concentration of Budesonide(Week 2, 4, or 8, or at the Final Treatment Evaluation)
- Mean Change in Blood Pressure (BP) at End of Treatment(Baseline, 12 weeks after the start of treatment)
- Change From Baseline in Physician's Global Assessment Score of Disease Severity(Baseline, 12 weeks after the start of treatment)
- Area Under The Plasma Concentration-Time Curve (AUC) of Budesonide From Time Zero to Time of The Last Measurable Concentration (AUC0-last)(Week 2, 4, or 8, or at the Final Treatment Evaluation)
- Maximum Plasma Concentration (Cmax) of Budesonide(Week 2, 4, or 8, or at the Final Treatment Evaluation)
- Percent of Participants With Potential Corticosteroid-Related Treatment-Emergent Adverse Events (TEAEs)(15 weeks after the start of treatment)