OBS in Adolescent and Adults With EOE: A Phase II, Randomized, Double-Blind, Placebo Controlled, Study With an Open Label Extension

Phase 2

Completed

Conditions: Eosinophilic Esophagitis (EoE)

Interventions: Drug: Placebo
Drug: Oral Budesonide Suspension (MB-9)

Registration Number: NCT01642212

Lead Sponsor: Shire

Brief Summary: This is a clinical trial to test an experimental drug for the treatment of Eosinophilic Esophagitis (EoE)

Detailed Description: Eosinophilic Esophagitis (EoE) is an inflammatory disorder of the esophagus and is a recognized clinical entity. Symptoms include feeding problems, heartburn, regurgitation, vomiting, abdominal pain and food impaction. The symptoms of EoE may be similar to gastroesophageal reflux disease (GERD) but do not resolve with gastric acid suppression. EoE is defined histologically as the presence of \> 15 intraepithelial eosinophils per high power fields on one or more esophageal biopsy specimens.

This Phase II study is comparing oral budesonide (OBS) to placebo to demonstrate that OBS induces a histologic response and a symptom response using a Dysphagia Symptom Questionnaire over a 16 week course of therapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 93

Inclusion Criteria

Males and Females, age 11-40
Histologic evidence of EoE
History of clinical symptoms of EoE including dysphagia
Willing to continue with dietary, environmental or medical therapy
Ability to read and understand english
Written Consent

Exclusion Criteria

Any Medical condition that may compromise the safety of the subjects or interfere with the signs and symptoms of EoE
Use of immunomodulatory therapy
Current use of swallowed corticosteroids
Esophageal strictures,varices or upper GI bleed
Other current diseases of the GI tract
Current viral infection or immunodeficiency condition
Pregnancy
Hypersensitivity to budesonide
History of non compliance

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Placebo	Taken once or twice daily for 20 weeks
Oral Budesonide Suspension	Oral Budesonide Suspension (MB-9)	Taken once or twice daily for up to 40 weeks

Primary Outcome Measures

Name	Time	Method
Percent of Participants Who Were Histologic Responders	Week 16	Histologic response was defined as a peak eosinophil count \</= 6/high power field (light microscopy) (HPF) across all esophageal levels at the final treatment evaluation (Week 16). An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value. Histopathology data were collected in a blinded fashion.
Change From Baseline in The Dysphagia Symptom Questionnaire (DSQ) Score at The Final Treatment Period Evaluation	Baseline, Week 16	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing).The DSQ score was calculated based on responses to Questions 2 and 3 \[14 x (sum of points from Questions 2 and 3 in the daily DSQ)/number of diaries with non-missing data\]. Baseline was the DSQ score of the 14-day period before randomization. A negative change from baseline indicates that symptoms decreased.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level at The Final Treatment Period Evaluation	Baseline, Week 16	An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value across all available esophagus levels. Histopathology data were collected in a blinded fashion. Baseline was defined as the score at screening. A negative change from baseline indicates that eosinophil count decreased.
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation	Week 16	The EoE survey assessed the following symptoms: heartburn, chest pain, regurgitation, abdominal pain, nausea, and vomiting. Participants indicated, by checking a box, if they had a change in symptoms (excluding dysphasia or food impaction) within the past 2 weeks. Baseline was defined as the assessment before randomization. Responses were as follows regarding symptoms at the final treatment evaluation: Improved - participant reported a specific symptom at baseline, but changed to no specific symptom ('Yes' to 'No'); No change - participant reported or did not report a specific symptom at both baseline and the final treatment evaluation; Worsened -participant did not report a specific symptom at baseline, but changed to report that specific symptom ('No' to 'Yes').
Change From Baseline in The DSQ Score Over Time	Baseline, Weeks 8 and 12	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing).The DSQ score was calculated based on responses to Questions 2 and 3 \[14 x (sum of points from Questions 2 and 3 in the daily DSQ)/number of diaries with non-missing data\]. Baseline was the DSQ score of the 14-day period before randomization. A negative change from baseline indicates that symptoms decreased.
Percent of Participants With a >/= 30% And >/= 50% Reduction In The DSQ Score From Baseline to The Final Treatment Period Evaluation	Baseline, Week 16	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing).The DSQ score was calculated based on responses to Questions 2 and 3 \[14 x (sum of points from Questions 2 and 3 in the daily DSQ)/number of diaries with non-missing data\]. Baseline was the DSQ score of the 14-day period before randomization.
Change From Baseline in The Physician's Global Assessment (PGA) of Disease Activity at The Final Treatment Period Evaluation	Baseline, Week 16	The physician Investigator (or qualified physician's assistant or nurse practitioner) completed the PGA to provide the global assessment of eosinophilic esophagitis (EoE) disease activity using a 0 to 100 mm visual analog scale (VAS) scale. The VAS is a 100 mm horizontal line on which the right extreme (100) is labeled "worst possible disease activity" and the left extreme (0) is labeled "no disease activity". The PGA raters were instructed to consider the line for the VAS a continuum with their own medical opinion or judgment of extremes on either end and to draw a vertical line at a point that best approximates the participant's current level of EoE disease activity. A negative change from baseline indicates that disease activity decreased.
Percent of Participants With New Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	Week 16	This outcome assessed the symptoms of participants who were symptom-free at baseline. The EoE survey assessed the following symptoms: heartburn, chest pain, regurgitation, abdominal pain, nausea, and vomiting. Participants indicated, by checking a box, if they had a change in symptoms (excluding dysphasia or food impaction) within the past 2 weeks. Baseline was defined as the assessment before randomization. Responses were as follows regarding symptoms at the final treatment evaluation: No change - participant reported or did not report a specific symptom at both baseline and the final treatment evaluation; Worsened -participant did not report any symptom at baseline, but changed to report at least 1 symptom at the final treatment evaluation.
Change From Baseline in The DSQ Score For The 50th Percentile of Participants at The Final Treatment Period Evaluation	Baseline, Week 16	A cumulative distribution function curve was constructed to illustrate the cumulative proportion of participants (x-axis) vs. the change in the DSQ score from baseline to the final treatment evaluation (y-axis). The 50th percentile is participants with a DSQ score that is in the middle of the distribution of all scores. A negative change from baseline indicates that symptoms decreased.
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	Week 16	The EoE survey assessed the following symptoms: heartburn, chest pain, regurgitation, abdominal pain, nausea, and vomiting. Participants indicated, by checking a box, if they had a change in symptoms (excluding dysphasia or food impaction) within the past 2 weeks. Baseline was defined as the assessment before randomization. Responses were as follows regarding symptoms at the final treatment evaluation: Improved - participant reported a specific symptom at baseline, but changed to no specific symptom ('Yes' to 'No'); No change - participant reported or did not report a specific symptom at both baseline and the final treatment evaluation; Worsened -participant did not report a specific symptom at baseline, but changed to report that specific symptom ('No' to 'Yes').
Change From Baseline in The Scores of DSQ Question 4 During The Treatment Period	Baseline, Weeks 8, 12, and 16	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). Question 4 is rated as None, I had no pain (score=0), mild pain (score=1), moderate pain (score=2), severe pain (score=3), or very severe pain (score=4); 4 is the worst pain. Baseline was the DSQ score of the 14-day period before randomization. A negative change from baseline indicates that symptoms decreased.
Percent of Participants With a Peak Eosinophil Count </= 15/High Power Field (Light Microscopy) (HPF) And </= 1/HPF at The Final Treatment Period Evaluation	Week 16	An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value across all available esophagus levels. Histopathology data were collected in a blinded fashion. The values reported are for participants with histologic response.
Percent of Participants Who Were Overall Responders at The Final Treatment Period Evaluation	Week 16	Overall response was defined as a reduction in the 2-week DSQ score of \>/= 30% and \>/= 50% from baseline to the final treatment period evaluation and a peak eosinophil count of \</= 6/high power field (light microscopy) (HPF) across all available esophageal levels at the final treatment period evaluation. An independent, central pathologist determined the peak eosinophil count from the proximal, mid-, and distal levels and selected the maximum peak value. Histopathology data were collected in a blinded fashion.
Change From Baseline in The Histopathologic Epithelial Features Combined Total Score at The Final Treatment Period Evaluation	Baseline, Week 16	Each esophageal biopsy specimen was evaluated microscopically by an independent, central pathologist for signs of epithelial inflammation and lamina propria fibrosis. Histopathologic epithelial features of each available esophageal level biopsy consisting of basal layer hyperplasia, eosinophil peak, dilated intercellular spaces, eosinophil microabcesses, surface layering, surface alteration, and apoptotic epithelial cells were scored and summed. Histopathology data were collected in a blinded fashion. Histopathology epithelial features were scored for both grade and stage. Each feature had a possible score of 0-3 for grade as well as stage. Thus each of the 3 levels had a possible score of 21, and a possible total grade or stage score of 63 for a maximum combined score of 126. The grade and stage score of the lamina propria was not included because the biopsy material was not available. A negative change from baseline indicates that epithelial inflammation decreased.
Percent of Days That Participants Reported That They Avoided Solid Food During The Baseline And Treatment Periods	From 14 days prior to the baseline visit to the final treatment period evaluation	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). Values were calculated for all the days that Question 1 was answered from 14 days prior to baseline visit up to the final treatment period evaluation.
Change From Baseline in The Total Endoscopy Score at The Final Treatment Period Evaluation	Baseline, Week 16	The gross endoscopic appearance of the esophageal surface was evaluated by a blinded study center physician. Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 major categories, including exudates or plaques, fixed esophageal rings, edema, furrows, and strictures. The endoscopy score was the sum of the scores for the 5 major categories - grade 0-1 for strictures; grade 0-2 for exudates or plaques, edema, and furrows; and grade 0-3 for fixed esophageal rings for the proximal and distal locations. The maximum endoscopy score was 10 points for each location (proximal and distal), and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points). Baseline was defined as the endoscopy score at screening. A negative change from baseline indicates that appearance improved.
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation	Week 16	Participants evaluated the change in their dysphasia (food passing slowly/difficulty swallowing) since the start of the study (screening) by choosing 1 of 7 responses on the PGIC survey: much worse (-3), worse (-2), a little worse (-1), no change (0), a little better (1), better (2), or much better (3). The values reported are the percent of participants who chose that response.
Percent of Participants Who Were Symptom Responders on The DSQ+Pain Scale at The Final Treatment Period Evaluation	Week 16	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Question 1 (did you eat solid food) and Question 2 (did food pass slowly or get stuck). If the answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Question 3 (did you have to do anything to make the food go down or get relief) and Question 4 (extent to which the participant experienced pain while swallowing).The DSQ+pain response was defined as a \>/= 30% and \>/= 50% reduction from baseline in the combined score from Questions 2, 3, and 4. The 2-week DSQ+pain score was calculated by adding points from Questions 2, 3, and 4 and then taking the average of the available scores over each 2-week interval.
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	Week 16	The EoE survey assessed the following symptoms: heartburn, chest pain, regurgitation, abdominal pain, nausea, and vomiting. Participants indicated, by checking a box, if they had a change in symptoms (excluding dysphasia or food impaction) within the past 2 weeks. Baseline was defined as the assessment before randomization. Responses were as follows regarding symptoms at the final treatment evaluation: Improved - participant reported a specific symptom at baseline, but changed to no specific symptom ('Yes' to 'No'); No change - participant reported or did not report a specific symptom at both baseline and the final treatment evaluation; Worsened -participant did not report a specific symptom at baseline, but changed to report that specific symptom ('No' to 'Yes').
Percent of Participants Without Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	Week 16	This outcome assessed the symptoms of participants who were symptom-free at baseline. The EoE survey assessed the following symptoms: heartburn, chest pain, regurgitation, abdominal pain, nausea, and vomiting. Participants indicated, by checking a box, if they had a change in symptoms (excluding dysphasia or food impaction) within the past 2 weeks. Baseline was defined as the assessment before randomization. Responses were as follows regarding symptoms at the final treatment evaluation: No change - participant did not report a specific symptom at both baseline and the final treatment evaluation; Worsened -participant did not report any symptom at baseline, but changed to report at least 1 symptom at the final treatment evaluation.
Change From Baseline in The Scores of DSQ Question 1 During The Treatment Period	Baseline, Weeks 8, 12, and 16	Participants' dysphagia symptoms were evaluated using the 4-item DSQ. The questionnaire was developed by the Sponsor, as an ePRO measure, according to the principles of the Final Guidance for Industry for Patient Reported Outcome Measures (PRO Guidance December 2009). All participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). Question 1 is rated as Yes (score=0) or No (score=1); higher values indicate a worse outcome. Baseline was the DSQ score of the 14-day period before randomization. A negative change from baseline indicates that symptoms decreased.

Trial Locations

Locations (23): University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Children's Center for Digestive Health
🇺🇸
Greenville, South Carolina, United States
Children's Memorial Hospital
🇺🇸
Chicago, Illinois, United States
UCSD Rady Children's Hospital
🇺🇸
San Diego, California, United States
Children's Center for Digestive Healthcare
🇺🇸
Atlanta, Georgia, United States
Northwestern Scool of Medicine
🇺🇸
Chicago, Illinois, United States
Center for Children's Digestive Health
🇺🇸
Park Ridge, Illinois, United States
Indiana University Health University Hospital
🇺🇸
Indianapolis, Indiana, United States
The Cincinnati Center for Eosinophilic Disorders
🇺🇸
Cincinnati, Ohio, United States
The Children's Hospital
🇺🇸
Aurora, Colorado, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
The Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Utah Healthcare
🇺🇸
Salt Lake City, Utah, United States
Phoenix Children's Hospital
🇺🇸
Phoenix, Arizona, United States
Children's Hospital Boston
🇺🇸
Boston, Massachusetts, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Great Lakes Gastroenterology
🇺🇸
Mentor, Ohio, United States
Carilion Pediatric Gastroenterology
🇺🇸
Roanoke, Virginia, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States