Trial Outcomes & Findings for OBS in Adolescent and Adults With EOE: A Phase II, Randomized, Double-Blind, Placebo Controlled, Study With an Open Label Extension (NCT NCT01642212)

Last Updated: 2021-06-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

Week 16

Results posted on

2021-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	Single-blind Placebo Eligible participants entered a 4-week, single-blind, placebo baseline period. Participants ingested the first dose of placebo in the clinic in the presence of study center personnel, and the remaining doses were ingested at home. Participants took placebo twice daily (bid); once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Placebo Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Placebo to Open-label Oral Budesonide Suspension (OBS) 2 mg During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.	Oral Budesonide Suspension (OBS) 2 mg to Open-label OBS 2 mg During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.
Single-blind Baseline STARTED	119	0	0	0	0
Single-blind Baseline COMPLETED	93	0	0	0	0
Single-blind Baseline NOT COMPLETED	26	0	0	0	0
Double-blind Treatment STARTED	0	42	51	0	0
Double-blind Treatment COMPLETED	0	39	49	0	0
Double-blind Treatment NOT COMPLETED	0	3	2	0	0
Open-label Extension STARTED	0	0	0	37	45
Open-label Extension COMPLETED	0	0	0	27	37
Open-label Extension NOT COMPLETED	0	0	0	10	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Single-blind Placebo Eligible participants entered a 4-week, single-blind, placebo baseline period. Participants ingested the first dose of placebo in the clinic in the presence of study center personnel, and the remaining doses were ingested at home. Participants took placebo twice daily (bid); once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Placebo Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Placebo to Open-label Oral Budesonide Suspension (OBS) 2 mg During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.	Oral Budesonide Suspension (OBS) 2 mg to Open-label OBS 2 mg During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.
Single-blind Baseline Did Not Meet Eligibility Criteria	26	0	0	0	0
Double-blind Treatment Other	0	2	1	0	0
Double-blind Treatment Non-compliance	0	1	0	0	0
Double-blind Treatment Adverse Event	0	0	1	0	0
Open-label Extension Adverse Event	0	0	0	3	0
Open-label Extension Sponsor Decision	0	0	0	7	4
Open-label Extension Consent Withdrawn	0	0	0	0	2
Open-label Extension Lost to Follow-up	0	0	0	0	1
Open-label Extension Other	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind Placebo n=42 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=51 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Total n=93 Participants Total of all reporting groups
Age, Continuous	20.8 years STANDARD_DEVIATION 7.50 • n=99 Participants	22.3 years STANDARD_DEVIATION 7.92 • n=107 Participants	21.6 years STANDARD_DEVIATION 7.73 • n=206 Participants
Age, Customized <18 Years Of Age	17 Participants n=99 Participants	18 Participants n=107 Participants	35 Participants n=206 Participants
Age, Customized >/= 18 Years Of Age	25 Participants n=99 Participants	33 Participants n=107 Participants	58 Participants n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	16 Participants n=107 Participants	29 Participants n=206 Participants
Sex: Female, Male Male	29 Participants n=99 Participants	35 Participants n=107 Participants	64 Participants n=206 Participants

PRIMARY outcome

Timeframe: Week 16

Population: The modified Intent-to-Treat (MITT) Analysis Set: all randomized participants who received at least 1 dose of double-blind study drug and had both an evaluable post-baseline biopsy during the treatment period and a post-baseline DSQ score. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants Who Were Histologic Responders	2.6 percent of participants	38.8 percent of participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: The MITT Analysis Set: all randomized participants who received at least 1 dose of double-blind study drug and had both an evaluable post-baseline biopsy during the treatment period and a post-baseline DSQ score. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.

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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Dysphagia Symptom Questionnaire (DSQ) Score at The Final Treatment Period Evaluation	-7.53 scores on a scale Standard Error 1.910	-14.27 scores on a scale Standard Error 1.682

SECONDARY outcome

Timeframe: Baseline, Weeks 8 and 12

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The DSQ Score Over Time Week 8, n = 37, 49	-4.92 scores on a scale Standard Error 1.673	-7.41 scores on a scale Standard Error 1.453
Change From Baseline in The DSQ Score Over Time Week 12, n = 36, 49	-7.42 scores on a scale Standard Error 2.065	-10.33 scores on a scale Standard Error 1.770

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The DSQ Score For The 50th Percentile of Participants at The Final Treatment Period Evaluation	-6.35 scores on a scale	-11.20 scores on a scale

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With a Peak Eosinophil Count </= 15/High Power Field (Light Microscopy) (HPF) And </= 1/HPF at The Final Treatment Period Evaluation </= 15 Eosinophils/HPF	7.9 percent of participants	46.9 percent of participants
Percent of Participants With a Peak Eosinophil Count </= 15/High Power Field (Light Microscopy) (HPF) And </= 1/HPF at The Final Treatment Period Evaluation </= 1 Eosinophils/HPF	0 percent of participants	30.6 percent of participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With a >/= 30% And >/= 50% Reduction In The DSQ Score From Baseline to The Final Treatment Period Evaluation >/= 50% DSQ Score Reduction	39.5 percent of participants	63.3 percent of participants
Percent of Participants With a >/= 30% And >/= 50% Reduction In The DSQ Score From Baseline to The Final Treatment Period Evaluation >/= 30% DSQ Score Reduction	44.7 percent of participants	69.4 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants Who Were Overall Responders at The Final Treatment Period Evaluation Responder and >/= 30% DSQ Score Reduction	2.6 percent of participants	26.5 percent of participants
Percent of Participants Who Were Overall Responders at The Final Treatment Period Evaluation Responder and >/= 50% DSQ Score Reduction	2.6 percent of participants	20.4 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Histopathologic Epithelial Features Combined Total Score at The Final Treatment Period Evaluation	-1.41 scores on a scale Standard Error 2.970	-23.75 scores on a scale Standard Error 2.602

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Total Endoscopy Score at The Final Treatment Period Evaluation	0.19 scores on a scale Standard Error 0.530	-3.58 scores on a scale Standard Error 0.466

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level at The Final Treatment Period Evaluation Proximal, n = 32, 45	-30.06 eosinophils/HPF Standard Error 6.798	-65.56 eosinophils/HPF Standard Error 5.704
Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level at The Final Treatment Period Evaluation Mid-, n = 36, 46	-17.34 eosinophils/HPF Standard Error 9.244	-76.90 eosinophils/HPF Standard Error 8.173
Change From Baseline in The Peak Eosinophil Count at Each Available Esophageal Level at The Final Treatment Period Evaluation Distal, n = 38, 49	-1.90 eosinophils/HPF Standard Error 9.852	-69.28 eosinophils/HPF Standard Error 8.667

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Physician's Global Assessment (PGA) of Disease Activity at The Final Treatment Period Evaluation	-10.16 scores on a scale Standard Error 4.199	-28.61 scores on a scale Standard Error 3.695

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation Much Worse	0 percent of participants	0 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation Worse	2.6 percent of participants	2.1 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation A Little Worse	13.2 percent of participants	2.1 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation No Change	15.8 percent of participants	12.5 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation A Little Better	28.9 percent of participants	25.0 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation Better	28.9 percent of participants	25.0 percent of participants
Distribution of Responses For The Patient Global Impression of Change (PGIC) Survey at The Final Treatment Evaluation Much Better	10.5 percent of participants	33.3 percent of participants

SECONDARY outcome

Timeframe: 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').

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Heartburn	10.5 percent of participants	18.4 percent of participants
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Chest Pain	23.7 percent of participants	18.4 percent of participants
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Regurgitation	15.8 percent of participants	20.4 percent of participants
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Abdominal Pain	15.8 percent of participants	10.2 percent of participants
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Nausea	10.5 percent of participants	16.3 percent of participants
Percent of Participants With Improved Symptoms on The Eosinophilic Esophagitis (EoE) Symptom Survey at The Final Treatment Period Evaluation Vomiting	5.3 percent of participants	4.1 percent of participants

SECONDARY outcome

Timeframe: Week 16

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Heartburn	86.8 percent of participants	71.4 percent of participants
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Chest Pain	68.4 percent of participants	71.4 percent of participants
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Regurgitation	71.1 percent of participants	73.5 percent of participants
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Abdominal Pain	76.3 percent of participants	85.7 percent of participants
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Nausea	86.8 percent of participants	77.6 percent of participants
Percent of Participants With No Change in Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Vomiting	81.6 percent of participants	91.8 percent of participants

SECONDARY outcome

Timeframe: Week 16

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Heartburn	2.6 percent of participants	10.2 percent of participants
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Chest Pain	7.9 percent of participants	10.2 percent of participants
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Regurgitation	13.2 percent of participants	6.1 percent of participants
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Abdominal Pain	7.9 percent of participants	4.1 percent of participants
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Nausea	2.6 percent of participants	6.1 percent of participants
Percent of Participants With Worsened Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation Vomiting	13.2 percent of participants	4.1 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants Without Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	71.1 percent of participants	83.7 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants With New Symptoms on The EoE Symptom Survey at The Final Treatment Period Evaluation	28.9 percent of participants	16.3 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Participants Who Were Symptom Responders on The DSQ+Pain Scale at The Final Treatment Period Evaluation >/= 30% DSQ+pain Score Reduction	47.4 percent of participants	67.3 percent of participants
Percent of Participants Who Were Symptom Responders on The DSQ+Pain Scale at The Final Treatment Period Evaluation >/= 50% DSQ+pain Score Reduction	39.5 percent of participants	65.3 percent of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Percent of Days That Participants Reported That They Avoided Solid Food During The Baseline And Treatment Periods	1.2 percentage of days Interval 0.0 to 1.1	0.7 percentage of days Interval 0.0 to 1.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Scores of DSQ Question 1 During The Treatment Period Week 8, n = 37, 49	0.02 scores on a scale Standard Error 0.050	-0.08 scores on a scale Standard Error 0.043
Change From Baseline in The Scores of DSQ Question 1 During The Treatment Period Week 12, n = 36, 49	0.05 scores on a scale Standard Error 0.091	0.02 scores on a scale Standard Error 0.078
Change From Baseline in The Scores of DSQ Question 1 During The Treatment Period Week 16, n = 38, 49	0.05 scores on a scale Standard Error 0.079	0.06 scores on a scale Standard Error 0.069

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=38 Participants Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=49 Participants Participants took 2 mg OBS (formulation MB-9) twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.
Change From Baseline in The Scores of DSQ Question 4 During The Treatment Period Week 8, n = 37, 47	-2.52 scores on a scale Standard Error 0.778	-3.25 scores on a scale Standard Error 0.690
Change From Baseline in The Scores of DSQ Question 4 During The Treatment Period Week 12, n = 36, 47	-2.97 scores on a scale Standard Error 0.775	-4.89 scores on a scale Standard Error 0.678
Change From Baseline in The Scores of DSQ Question 4 During The Treatment Period Week 16, n = 38, 47	-3.08 scores on a scale Standard Error 0.824	-4.87 scores on a scale Standard Error 0.741

Adverse Events

Double-blind Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Double-blind Oral Budesonide Suspension (OBS) 2 mg

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo to Open-label Oral Budesonide Suspension (OBS) 2 mg

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Oral Budesonide Suspension (OBS) 2 mg to Open-label OBS 2 mg

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind Placebo n=42 participants at risk Participants took placebo twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Double-blind Oral Budesonide Suspension (OBS) 2 mg n=51 participants at risk Participants took 2mg OBS (formulation MB-9) 2 mg twice daily (bid) at home for 12 weeks. Study drug was administered once in the morning after breakfast and once in the evening at bedtime; the volume per dose was 10 mL of oral liquid.	Placebo to Open-label Oral Budesonide Suspension (OBS) 2 mg n=37 participants at risk During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.	Oral Budesonide Suspension (OBS) 2 mg to Open-label OBS 2 mg n=45 participants at risk During the first 12 weeks of open-label extension treatment, participants took 2 mg OBS (formulation MB-9) once daily (qd) at bedtime. The volume per dose was 10 mL of oral liquid (10 mL qd; 0.2 mg/mL). Thereafter, an optional dose increase to 1.5 mg twice daily (bid) (7.5 mL bid; 0.2 mg/mL) and then to 2 mg bid (10 mL bid; 0.2 mg/mL) was allowed for subjects whose response to the 2 mg once daily dose was inadequate, as determined by the Investigator; a dose decrease to 2 mg once daily was allowed at any time.
Gastrointestinal disorders Food poisoning	0.00% 0/42 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	2.0% 1/51 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/37 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/45 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/42 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/51 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	2.7% 1/37 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/45 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/42 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/51 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	2.7% 1/37 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.	0.00% 0/45 This section reports treatment-emergent AEs (TEAEs) for the Safety Analysis Set, which was defined as all randomized participants who received at least 1 dose of double-blind study drug (placebo or OBS). Adverse events experienced during the placebo baseline period were defined as events that began before the first dose of double-blind study drug.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER