Trial Outcomes & Findings for SOFEED: Six Food vs. One Food Eosinophilic Esophagitis Diet Study (NCT NCT02778867)

NCT ID: NCT02778867

Last Updated: 2020-05-26

Results Overview

Percent of participants in histologic remission in 1FED versus 6FED groups. Remission is defined as esophageal peak eosinophil count \< 15 eosinophils per high powered field (eos/hpf)

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 129 participants
• Primary outcome timeframe: 6 weeks after starting treatment
• Results posted on: 2020-05-26

Participant Flow

Participants were recruited from eosinophilic esophagitis specialty clinics (10 sites) in the USA between May 20, 2016 and March 2019

143 participants screened, 14 excluded (8 did not meet inclusion criteria, 1 met exclusion criteria, 5 withdrew during screening), and 129 randomized

Participant milestones

Measure	1-Food Elimination Diet (1FED) Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy	1FED Non-Responders (6FED) Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 2 6 Food Elimination Diet Therapy	6FED Non-responders (SGC) Participants that fail to respond to 6FED in Phase 1 administer swallowed glucocorticoids (SGC) (Flovent HFA) 880 mcg twice daily in Phase 2 Fluticasone Propionate, 880 mcg twice daily
Phase 1 STARTED	67	62	0	0
Phase 1 COMPLETED	65	59	0	0
Phase 1 NOT COMPLETED	2	3	0	0
Phase 2 STARTED	0	0	21	11
Phase 2 COMPLETED	0	0	20	9
Phase 2 NOT COMPLETED	0	0	1	2

Reasons for withdrawal

Measure	1-Food Elimination Diet (1FED) Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy	1FED Non-Responders (6FED) Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 2 6 Food Elimination Diet Therapy	6FED Non-responders (SGC) Participants that fail to respond to 6FED in Phase 1 administer swallowed glucocorticoids (SGC) (Flovent HFA) 880 mcg twice daily in Phase 2 Fluticasone Propionate, 880 mcg twice daily
Phase 1 Withdrawal by Subject	2	3	0	0
Phase 2 Withdrawal by Subject	0	0	1	0
Phase 2 Physician Decision	0	0	0	1
Phase 2 Adverse Event	0	0	0	1

Baseline Characteristics

Clinical counts were used for study entry. Research counts (shown here) were unable to be obtained for some subjects.

Baseline characteristics by cohort

Measure	1-Food Elimination Diet (1FED) n=67 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=62 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy	Total n=129 Participants Total of all reporting groups
Age, Continuous	36.4 years STANDARD_DEVIATION 10.2 • n=67 Participants	37.8 years STANDARD_DEVIATION 10.4 • n=62 Participants	37.0 years STANDARD_DEVIATION 10.3 • n=129 Participants
Sex: Female, Male Female	30 Participants n=67 Participants	29 Participants n=62 Participants	59 Participants n=129 Participants
Sex: Female, Male Male	37 Participants n=67 Participants	33 Participants n=62 Participants	70 Participants n=129 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=67 Participants	1 Participants n=62 Participants	2 Participants n=129 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=67 Participants	61 Participants n=62 Participants	126 Participants n=129 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=67 Participants	0 Participants n=62 Participants	1 Participants n=129 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=67 Participants	0 Participants n=62 Participants	0 Participants n=129 Participants
Race (NIH/OMB) Asian	2 Participants n=67 Participants	0 Participants n=62 Participants	2 Participants n=129 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=67 Participants	0 Participants n=62 Participants	0 Participants n=129 Participants
Race (NIH/OMB) Black or African American	0 Participants n=67 Participants	1 Participants n=62 Participants	1 Participants n=129 Participants
Race (NIH/OMB) White	63 Participants n=67 Participants	61 Participants n=62 Participants	124 Participants n=129 Participants
Race (NIH/OMB) More than one race	1 Participants n=67 Participants	0 Participants n=62 Participants	1 Participants n=129 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=67 Participants	0 Participants n=62 Participants	1 Participants n=129 Participants
Region of Enrollment United States	67 participants n=67 Participants	62 participants n=62 Participants	129 participants n=129 Participants
Peak Eosinophil Count	56 eosinophils per high power field n=64 Participants • Clinical counts were used for study entry. Research counts (shown here) were unable to be obtained for some subjects.	38 eosinophils per high power field n=59 Participants • Clinical counts were used for study entry. Research counts (shown here) were unable to be obtained for some subjects.	44 eosinophils per high power field n=123 Participants • Clinical counts were used for study entry. Research counts (shown here) were unable to be obtained for some subjects.
Histology scoring system	0.83 score on a scale STANDARD_DEVIATION 0.26 • n=64 Participants • Histology scoring system scores were not obtained for some subjects at baseline (slides were unavailable)	0.81 score on a scale STANDARD_DEVIATION 0.25 • n=59 Participants • Histology scoring system scores were not obtained for some subjects at baseline (slides were unavailable)	0.82 score on a scale STANDARD_DEVIATION 0.26 • n=123 Participants • Histology scoring system scores were not obtained for some subjects at baseline (slides were unavailable)
Endoscopic Reference Score	7.0 score on a scale n=57 Participants • Baseline endoscopic feature scores were not obtained on some subjects	6.5 score on a scale n=46 Participants • Baseline endoscopic feature scores were not obtained on some subjects	7.0 score on a scale n=103 Participants • Baseline endoscopic feature scores were not obtained on some subjects

PRIMARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation post randomization. Participants whose histologic remission could not be determined were imputed as treatment failures.

Percent of participants in histologic remission in 1FED versus 6FED groups. Remission is defined as esophageal peak eosinophil count < 15 eosinophils per high powered field (eos/hpf)

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=67 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=62 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Percent of Participants in Histologic Remission (<15 Eos/Hpf)	34.3 percentage of participants	40.3 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation post randomization. Participants whose histologic remission could not be determined were imputed as treatment failures.

Percent of participants in complete and partial histologic remission in 1FED versus 6FED groups. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=67 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=62 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Percent of Participants in Complete and Partial Histologic Remission Complete remission (≤ 1eos/hpf)	6.0 percentage of participants	21.0 percentage of participants
Percent of Participants in Complete and Partial Histologic Remission Partial remission (2 - 14 eos/hpf)	28.4 percentage of participants	19.4 percentage of participants

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation in Phase 2. Participants whose histologic remission could not be determined were imputed as treatment failures.

Percent of participants who failed 6FED in Phase 1 in histologic remission after following swallowed glucocorticoids (SGC) in Phase 2. Remission is defined as esophageal peak eosinophil count < 15 eos/hpf

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=11 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Percent of Participants Following SGC in Histologic Remission in Phase 2	81.8 percentage of participants Interval 48.2 to 97.7	—

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation in Phase 2. Participants whose histologic remission could not be determined were imputed as treatment failures.

Percent of participants who failed 1FED in Phase 1 in histologic remission after following 6FED in Phase 2. Remission is defined as esophageal peak eosinophil count < 15 eos/hpf

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=21 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Percent of Participants Following 6FED in Histologic Remission in Phase 2	42.9 percentage of participants Interval 21.8 to 66.0	—

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation post randomization.

Peak eosinophil counts were obtained at baseline and 6 weeks. The maximum (highest) peak eosinophil count among distal, mid, and proximal esophageal biopsies was obtained. Change in peak eosinophil count is defined as peak count at 6 weeks minus peak count at baseline. Changes in peak count are compared between 1FED and 6FED. A reduction (negative change) in peak count indicates improvement.

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=64 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=59 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Change From Baseline in Peak Eosinophil Count	-18 eosinophils per high power field Interval -49.0 to 1.0	-22 eosinophils per high power field Interval -36.0 to -5.0

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation post randomization.

The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 (higher scores indicate more severe and/or extensive abnormalities). Histology scores were obtained at baseline and 6 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 6 weeks minus total HSS score at baseline. Changes in scores are compared between 1FED and 6FED. A reduction (negative change) in score indicates improvement.

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=64 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=59 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Change From Baseline in Total Histology Scoring System	-0.15 score on a scale Standard Deviation 0.39	-0.23 score on a scale Standard Deviation 0.34

SECONDARY outcome

Timeframe: 6 weeks after starting treatment

Population: Intent to treat analysis including participants who had at least one clinical observation post randomization.

The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 (higher scores indicate worsening features). Endoscopic features were assessed at baseline and 6 weeks. Change in total endoscopic reference score is defined as total score at 6 weeks minus total score at baseline. Changes in scores are compared between 1FED and 6FED. A reduction (negative change) in score indicates improvement.

Outcome measures

Measure	1-Food Elimination Diet (1FED) n=57 Participants Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=46 Participants Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy
Change From Baseline in Total Endoscopic Reference Score	-1.0 score on a scale Interval -4.0 to 0.0	-2.0 score on a scale Interval -4.0 to 1.0

Adverse Events

1-Food Elimination Diet (1FED)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

6-Food Elimination Diet (6FED)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

1FED Non-Responders (6FED)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

6FED Non-responders (SGC)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	1-Food Elimination Diet (1FED) n=67 participants at risk Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=62 participants at risk Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy	1FED Non-Responders (6FED) n=21 participants at risk Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 2 6 Food Elimination Diet (after 1FED failure)	6FED Non-responders (SGC) n=11 participants at risk Participants that fail to respond to 6FED in Phase 1 administer swallowed glucocorticoids (SGC) (Flovent HFA) 880 mcg twice daily in Phase 2 Fluticasone Propionate, 880 mcg twice daily (after 6FED failure)
Psychiatric disorders Suicidal ideation	0.00% 0/67 • From informed consent to 30 days after the cessation of treatment	0.00% 0/62 • From informed consent to 30 days after the cessation of treatment	0.00% 0/21 • From informed consent to 30 days after the cessation of treatment	9.1% 1/11 • From informed consent to 30 days after the cessation of treatment

Other adverse events

Measure	1-Food Elimination Diet (1FED) n=67 participants at risk Participants eliminate milk from the diet in Phase 1 1 Food Elimination Diet Therapy	6-Food Elimination Diet (6FED) n=62 participants at risk Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1 6 Food Elimination Diet Therapy	1FED Non-Responders (6FED) n=21 participants at risk Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 2 6 Food Elimination Diet (after 1FED failure)	6FED Non-responders (SGC) n=11 participants at risk Participants that fail to respond to 6FED in Phase 1 administer swallowed glucocorticoids (SGC) (Flovent HFA) 880 mcg twice daily in Phase 2 Fluticasone Propionate, 880 mcg twice daily (after 6FED failure)
Gastrointestinal disorders Gastrointestinal Pain	0.00% 0/67 • From informed consent to 30 days after the cessation of treatment	0.00% 0/62 • From informed consent to 30 days after the cessation of treatment	0.00% 0/21 • From informed consent to 30 days after the cessation of treatment	9.1% 1/11 • From informed consent to 30 days after the cessation of treatment
Gastrointestinal disorders Diarrhea	1.5% 1/67 • From informed consent to 30 days after the cessation of treatment	3.2% 2/62 • From informed consent to 30 days after the cessation of treatment	0.00% 0/21 • From informed consent to 30 days after the cessation of treatment	9.1% 1/11 • From informed consent to 30 days after the cessation of treatment
Infections and infestations Bronchial Infection	0.00% 0/67 • From informed consent to 30 days after the cessation of treatment	0.00% 0/62 • From informed consent to 30 days after the cessation of treatment	0.00% 0/21 • From informed consent to 30 days after the cessation of treatment	9.1% 1/11 • From informed consent to 30 days after the cessation of treatment
Endocrine disorders Adrenal insufficiency	0.00% 0/67 • From informed consent to 30 days after the cessation of treatment	0.00% 0/62 • From informed consent to 30 days after the cessation of treatment	0.00% 0/21 • From informed consent to 30 days after the cessation of treatment	9.1% 1/11 • From informed consent to 30 days after the cessation of treatment

Additional Information

Marc E. Rothenberg, MD, PhD

Cincinnati Children's Hospital Medical Center

Phone: 513-636-7177

Email: marc.rothenberg@cchmc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER