Trial Outcomes & Findings for A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved (NCT NCT02605837)

Results Overview

Histologic response was defined as a peak eosinophil count of less than or equal to (\<=) 6/ high-powered field (HPF) across all available esophageal levels at final treatment period evaluation (Week 16). Histologic response after 12 weeks of double blind treatment at Week 16 was reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

318 participants

Primary outcome timeframe

Week 16

Results posted on

2025-02-19

Participant Flow

This study was conducted at 72 sites in North America from 07 December 2015 (first participant enrolled) to 15 February 2019 (last participant completed).

A total of 318 participants were randomized and received the treatment (placebo or oral Budesonide suspension \[OBS\]) in a double blind fashion following a placebo lead-in phase and 296 participants completed the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Study STARTED	105	213
Overall Study COMPLETED	94	202
Overall Study NOT COMPLETED	11	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Overall Study Adverse Event	3	1
Overall Study Non-Compliance with Study Drug	0	1
Overall Study Withdrawal by Subject	8	8
Overall Study Physician Decision	0	1

Baseline Characteristics

A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.	Total n=318 Participants Total of all reporting groups
Age, Continuous	33.9 Years STANDARD_DEVIATION 12.13 • n=5 Participants	33.8 Years STANDARD_DEVIATION 11.89 • n=7 Participants	33.9 Years STANDARD_DEVIATION 11.95 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	84 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	129 Participants n=7 Participants	191 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants	204 Participants n=7 Participants	304 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	101 Participants n=5 Participants	200 Participants n=7 Participants	301 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Histologic response was defined as a peak eosinophil count of less than or equal to (\<=) 6/ high-powered field (HPF) across all available esophageal levels at final treatment period evaluation (Week 16). Histologic response after 12 weeks of double blind treatment at Week 16 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Histologic Response at the Final Treatment Period Evaluation (Week 16) Histology Response - Yes	1 Participants	113 Participants
Number of Participants With Histologic Response at the Final Treatment Period Evaluation (Week 16) Histology Response - No	104 Participants	100 Participants

PRIMARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Dysphagia symptom response was defined as greater than or equal to (\>=) 30 percent (%) reduction in the Dysphagia Symptom Questionnaire (DSQ) combined score (questions 2+3). DSQ contained 4 questions, 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). DSQ score= (\[sum of points from questions 2+3 in the daily DSQ\]×14)/ Number of diaries reported with non-missing data. Dysphagia symptom response after 12 weeks of double blind treatment at Week 16 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Dysphagia Symptom Response at the Final Treatment Period Evaluation (Week 16) Dysphagia symptom response: Yes	41 Participants	112 Participants
Number of Participants With Dysphagia Symptom Response at the Final Treatment Period Evaluation (Week 16) Dysphagia symptom response: No	64 Participants	101 Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

DSQ contained 4 questions, 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). DSQ combined score= (\[sum of points from questions 2+3 in the daily DSQ\]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ after 12 weeks of double blind treatment at Week 16 was reported.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=197 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Combined Score at the Final Treatment Period Evaluation (Week 16)	-9.07 Score on scale Standard Error 1.519	-12.99 Score on scale Standard Error 1.202

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively 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 respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. Endoscopic findings after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=202 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in Total Endoscopy Score at the Final Treatment Period Evaluation (Week 16)	-2.2 score on scale Standard Error 0.38	-4.0 score on scale Standard Error 0.30

SECONDARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Participant was considered as responder at Week 16 if he/she had peak eosinophil count of \<15/HPF or \<=1/HPF across all esophagus levels. Number of participants with peak eosinophil count \< 15/HPF or \<=1/HPF after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16) Peak Eosinophil Count (<15/HPF): Responders	1 Participants	132 Participants
Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16) Peak Eosinophil Count (<15/HPF): Non-responders	104 Participants	81 Participants
Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16) Peak Eosinophil Count (<=1/HPF): Responders	0 Participants	69 Participants
Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16) Peak Eosinophil Count (<=1/HPF): Non-responders	105 Participants	144 Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure at each specific category.

Change from baseline in the peak eosinophil count after 12 weeks of double blind treatment at week 16 for each available esophageal level (proximal, mid, distal, maximum) were reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16) Proximal: Week 16	-5.5 eosinophil count Standard Error 3.19	-34.0 eosinophil count Standard Error 2.52
Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16) Mid: week 16	-12.9 eosinophil count Standard Error 3.74	-43.3 eosinophil count Standard Error 3.01
Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16) Distal: Week 16	-4.9 eosinophil count Standard Error 3.66	-38.0 eosinophil count Standard Error 2.88
Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16) Maximum: Week 16	-7.6 eosinophil count Standard Error 4.27	-55.2 eosinophil count Standard Error 3.37

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

Change from baseline in histopathologic epithelial features combined total score of grade and stage ratio after 12 weeks of double blind treatment at Week 16 were reported by measuring eight histopathologic epithelial features: basal layer hyperplasia, eosinophil density, eosinophil micro-abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, lamina propria fibrosis were scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (grade) and the amount of tissue affected by the abnormality (stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=201 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in the Histopathologic Epithelial Features Combined Total Score Ratio (TSR) at the Final Treatment Period Evaluation (Week 16) Grade - Combined TSR: Week 16	-0.03 score on scale Standard Error 0.016	-0.22 score on scale Standard Error 0.013
Change From Baseline in the Histopathologic Epithelial Features Combined Total Score Ratio (TSR) at the Final Treatment Period Evaluation (Week 16) Stage - Combined TSR: Week 16	-0.0 score on scale Standard Error 0.02	-0.2 score on scale Standard Error 0.01

SECONDARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Dysphagia symptom response (binary response \[i.e, responders versus. non-responders\]) was defined as a \>=50% reduction in the DSQ combined score (questions 2+3), from baseline to the final treatment period evaluation (Week 16). DSQ contained 4 questions, 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). DSQ score= (\[sum of points from questions 2+3 in the daily DSQ\]×14)/ Number of diaries reported with non-missing data. Number of participants with binary response after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Dysphagia Symptom Response (Binary Response) at the Final Treatment Period Evaluation (Week 16) Responders	35 Participants	88 Participants
Number of Participants With Dysphagia Symptom Response (Binary Response) at the Final Treatment Period Evaluation (Week 16) Non Responders	70 Participants	125 Participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Overall binary response I was defined as a reduction in the DSQ score of \>=30% from baseline to the final treatment period (week 16) evaluation and a peak eosinophil count of \<=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 30% reduction in DSQ combined score between baseline and Week 16 and has peak eosinophil count of \<=6/HPF across all esophagus levels. Number of participants with overall binary response I after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Overall Binary Response I at the Final Treatment Period Evaluation (Week 16) Overall Binary Response I: Responders	0 Participants	64 Participants
Number of Participants With Overall Binary Response I at the Final Treatment Period Evaluation (Week 16) Overall Binary Response I: Non Responders	105 Participants	149 Participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP.

Overall binary response II was defined as a reduction in the DSQ score of \>=50% from baseline to the final treatment period evaluation and a peak eosinophil count of \<=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 50% reduction in DSQ combined score between baseline and Week 16 and had peak eosinophil count of \<=6/HPF across all esophagus levels. Number of participants with overall binary response II after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=213 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Number of Participants With Overall Binary Response II at the Final Treatment Period Evaluation (Week 16) Overall binary response II: Responders	0 Participants	48 Participants
Number of Participants With Overall Binary Response II at the Final Treatment Period Evaluation (Week 16) Overall binary response II: Non-Responders	105 Participants	165 Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

DSQ contained 4 questions, 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). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= (\[sum of points from questions 2+3+4 in the daily DSQ\] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=197 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) + Pain Score (Questions 2 +3+4) at the Final Treatment Period Evaluation (Week 16)	-12.24 Score on scale Standard Error 2.097	-18.65 Score on scale Standard Error 1.660

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: FAS included all randomized participants who received at least one dose of a double-blind IP. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

DSQ pain score was calculated by summing the scores of responses to Question 4 (extent to which the participant experienced pain while swallowing) only, by using the following formula: DSQ pain score= \[(sum of points from question 4 in the daily DSQ)×14\]/ Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ pain score (question 4) after 12 weeks of double blind treatment at Week 16 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=89 Participants Participants received oral dose of 10 milliliter (ml) placebo matched with the Oral Budesonide Suspension (OBS) twice daily up to 16 weeks.	Oral Budesonide Suspension (OBS) n=197 Participants Post placebo lead in phase (4 weeks) participants received OBS 10 ml (2 mg) twice daily up to 12 weeks.
Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) Pain Score (Question 4) at the Final Treatment Period Evaluation (Week 16)	-3.01 score on scale Standard Error 0.751	-5.47 score on scale Standard Error 0.595

SECONDARY outcome

Timeframe: From start of study drug administration up to follow-up (Week 20)

Population: Safety analysis set included all participants who received at least one dose of any double-blind IP.

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that start or deteriorate on or after the first dose of double-blind IP (Week 44) and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact. Number of participants with TEAE's were reported.