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

Eosinophilic Esophagitis (EoE) Clinical Trial

Official title:

Oral Budesonide Suspension (OBS) in Adolescent and Adult Subjects (11-40 Years of Age)With Eosinophilic Esophagitis: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study With an Open Label Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01642212
• Other study ID #: MPI-101-06
• Status: Completed
• Phase: Phase 2
• Start date: July 23, 2012
• Est. completion date: October 30, 2014

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: October 30, 2014
• Est. primary completion date: October 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 11 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Eosinophilic Esophagitis (EoE)
• Esophagitis

Intervention

Drug:
• Oral Budesonide Suspension (MB-9)
OBS suspension to be taken bid over a 16 week course of double blind therapy and OBS suspension to be taken qd to bid during a 24 week optional open label extension period
• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants Who Were Histologic Responders	Histologic response was defined as a peak eosinophil count	Week 16
Primary	Change From Baseline in The Dysphagia Symptom Questionnaire (DSQ) Score at 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).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.	Baseline, Week 16
Secondary	Change From Baseline in The DSQ Score Over Time	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.	Baseline, Weeks 8 and 12
Secondary	Change From Baseline in The DSQ Score For The 50th Percentile of Participants at The Final Treatment Period Evaluation	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.	Baseline, Week 16
Secondary	Percent of Participants With a Peak Eosinophil Count </= 15/High Power Field (Light Microscopy) (HPF) And </= 1/HPF 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 across all available esophagus levels. Histopathology data were collected in a blinded fashion. The values reported are for participants with histologic response.	Week 16
Secondary	Percent of Participants With a >/= 30% And >/= 50% Reduction In The DSQ Score From Baseline 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).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.	Baseline, Week 16
Secondary	Percent of Participants Who Were Overall Responders at The Final Treatment Period Evaluation	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	Week 16
Secondary	Change From Baseline in The Histopathologic Epithelial Features Combined Total Score at The Final Treatment Period Evaluation	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.	Baseline, Week 16
Secondary	Change From Baseline in The Total Endoscopy Score at The Final Treatment Period Evaluation	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.	Baseline, Week 16
Secondary	Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level 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 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.	Baseline, Week 16
Secondary	Change From Baseline in The Physician's Global Assessment (PGA) of Disease Activity at The Final Treatment Period Evaluation	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.	Baseline, Week 16
Secondary	Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation	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.	Week 16
Secondary	Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation	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').	Week 16
Secondary	Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	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').	Week 16
Secondary	Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	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').	Week 16
Secondary	Percent of Participants Without Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	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.	Week 16
Secondary	Percent of Participants With New Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	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.	Week 16
Secondary	Percent of Participants Who Were Symptom Responders on The DSQ+Pain Scale at 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 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.	Week 16
Secondary	Percent of Days That Participants Reported That They Avoided Solid Food During The Baseline And Treatment Periods	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.	From 14 days prior to the baseline visit to the final treatment period evaluation
Secondary	Change From Baseline in The Scores of DSQ Question 1 During The Treatment Period	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.	Baseline, Weeks 8, 12, and 16
Secondary	Change From Baseline in The Scores of DSQ Question 4 During The Treatment Period	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.	Baseline, Weeks 8, 12, and 16