Trial Outcomes & Findings for An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE) (NCT NCT03029091)

Last Updated: 2020-09-09

Results Overview

Peak esophageal eosinophil counts were obtained at baseline and 16 weeks. Change in peak eosinophil count is defined as peak count at 16 weeks minus peak count at baseline. A reduction (negative change) in peak count indicates improvement. Peak count is defined as the highest count between the distal and proximal esophageal eosinophil counts.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Baseline, 16 weeks

Results posted on

2020-09-09

Participant Flow

Participants were recruited from eosinophilic esophagitis specialty clinics (3 sites) in the USA between May 2017 and April 2019.

17 participants screened, 2 excluded (2 met exclusion criteria), and 15 initiated the intervention

Participant milestones

Participant milestones
Measure	EoE + CTD Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Overall Study STARTED	8	7
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open-Label Trial of Losartan Potassium in Participants With Eosinophilic Esophagitis (EoE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EoE + CTD n=8 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan	Total n=15 Participants Total of all reporting groups
Age, Continuous	10.4 years STANDARD_DEVIATION 3.7 • n=5 Participants	13.8 years STANDARD_DEVIATION 5.0 • n=7 Participants	12.0 years STANDARD_DEVIATION 4.5 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 16 weeks

Population: Per protocol population (protocol violation excluded from data analysis)

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=14 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Change From Baseline in Peak Eosinophil Count Baseline	63.3 eosinophils per high power field Interval 41.4 to 85.2	67.7 eosinophils per high power field Interval 21.0 to 114.4	58.9 eosinophils per high power field Interval 37.5 to 80.2
Change From Baseline in Peak Eosinophil Count Change	-11.2 eosinophils per high power field Interval -36.9 to 14.5	-1.9 eosinophils per high power field Interval -40.6 to 36.9	-20.6 eosinophils per high power field Interval -65.2 to 24.0

PRIMARY outcome

Timeframe: 20 weeks after the start of treatment (16 weeks treatment and 4 weeks follow-up)

Population: Intent to treat analysis including participants enrolled in the study

The occurrence of serious adverse events and Grade 3 and higher adverse events from Week 0 to Week 20

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=15 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=8 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Number of Serious and Grade 3 or Higher Adverse Events Serious Adverse Events	0 events	0 events	0 events
Number of Serious and Grade 3 or Higher Adverse Events Grade 3 or higher adverse events	1 events	0 events	1 events

SECONDARY outcome

Timeframe: 16 weeks

Population: Per protocol population (protocol violation excluded from data analysis)

Percent of participants in complete and partial histologic remission. 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

Outcome measures
Measure	EoE +/- CTD n=14 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks Complete remission (≤ 1 eos/hpf)	7 percentage of subjects Interval 0.0 to 34.0	14 percentage of subjects Interval 0.0 to 58.0	0 percentage of subjects Interval 0.0 to 41.0
Percent of Participants in Complete and Partial Histologic Remission at 16 Weeks Partial remission (2 - 14 eos/hpf)	21 percentage of subjects Interval 5.0 to 51.0	14 percentage of subjects Interval 0.0 to 58.0	29 percentage of subjects Interval 4.0 to 71.0

SECONDARY outcome

Timeframe: Baseline, 16 weeks

Population: Per protocol population (protocol violation excluded from data analysis).

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 with higher scores indicating worse abnormalities. Histology scores were obtained at baseline and 16 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 16 weeks minus total HSS score at baseline. A reduction (negative change) in score indicates improvement.

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=14 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Change From Baseline in Total Histology Scoring System Baseline - Total HSS	0.79 score on a scale Interval 0.65 to 0.93	0.89 score on a scale Interval 0.69 to 1.09	0.70 score on a scale Interval 0.48 to 0.92
Change From Baseline in Total Histology Scoring System Change - Total HSS	-0.09 score on a scale Interval -0.28 to 0.1	-0.15 score on a scale Interval -0.47 to 0.17	-0.03 score on a scale Interval -0.33 to 0.28

SECONDARY outcome

Timeframe: Baseline, 16 weeks

Population: Per protocol population (protocol violation excluded from data analysis).

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 with higher scores indicating worse features. Endoscopic features were assessed at baseline and 16 weeks. Change in total endoscopic reference score is defined as total score at 16 weeks minus total score at baseline. A reduction (negative change) in score indicates improvement.

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=14 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Change From Baseline in Total Endoscopic Reference Score Baseline - EREFS Total Score	5.1 score on a scale Interval 3.6 to 6.7	5.4 score on a scale Interval 3.4 to 7.5	4.9 score on a scale Interval 1.9 to 7.9
Change From Baseline in Total Endoscopic Reference Score Change - EREFS Total Score	-1.3 score on a scale Interval -2.6 to 0.0	-1.7 score on a scale Interval -3.2 to -0.2	-0.9 score on a scale Interval -3.6 to 1.8

SECONDARY outcome

Timeframe: Baseline,16 weeks

Population: Per protocol population (protocol violation excluded from data analysis)

The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastroesophageal reflux, nausea/vomiting, and pain) as reported by their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 16 weeks. Change in score is defined as total score at 16 weeks minus total score at baseline as completed by parent proxy.

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=13 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=6 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Change From Baseline in PEESS V2.0 Baseline - PEESS Total Score	29.9 score on a scale Interval 15.5 to 44.4	32.7 score on a scale Interval 6.36 to 59.0	26.7 score on a scale Interval 6.3 to 47.1
Change From Baseline in PEESS V2.0 Change - PEESS Total Score	-9.7 score on a scale Interval -18.3 to -1.1	-12.5 score on a scale Interval -31.2 to 6.2	-6.89 score on a scale Interval -15.3 to 1.6

SECONDARY outcome

Timeframe: Baseline, 16 weeks

Population: Per protocol population (protocol violation excluded from data analysis)

The Pediatric Eosinophilic Esophagitis Quality of Life Inventory (PedsQL EoE) measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 16 weeks. Change in score is defined as the PedsQL EoE total score at 16 weeks minus total score at baseline as reported by parent proxy.

Outcome measures

Outcome measures
Measure	EoE +/- CTD n=13 Participants Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=7 Participants Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=6 Participants Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Change From Baseline in PedsQL EoE Baseline - PedsQL Total Score	74.4 score on a scale Interval 64.2 to 84.5	73.3 score on a scale Interval 58.7 to 87.8	75.6 score on a scale Interval 55.3 to 96.0
Change From Baseline in PedsQL EoE Change - PedsQL Total Score	6.7 score on a scale Interval -0.1 to 13.5	4.8 score on a scale Interval -7.5 to 17.1	9.0 score on a scale Interval -0.4 to 18.3

Adverse Events

EoE +/- CTD

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

EoE + CTD

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

EoE - CTD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Marc E. Rothenberg, MD, PhD

Cincinnati Children's Hospital Medical Center

Phone: 513 636-7177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	EoE +/- CTD n=15 participants at risk Participants with eosinophilic esophagitis (EoE) with and without connective tissue disorder (CTD) receive Losartan	EoE + CTD n=8 participants at risk Participants with eosinophilic esophagitis (EoE) with connective tissue disorder (CTD) receive Losartan	EoE - CTD n=7 participants at risk Participants with eosinophilic esophagitis (EoE) without connective tissue disorder (CTD) receive Losartan
Blood and lymphatic system disorders Neutropenia	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Eye disorders Conjunctivitis	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Gastrointestinal disorders Gastritis	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Gastrointestinal disorders Nausea	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Gastrointestinal disorders Vomiting	13.3% 2/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	25.0% 2/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Infections and infestations Upper Respiratory Infection	13.3% 2/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Infections and infestations Fever	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Infections and infestations Rhinitis Infective	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
General disorders Common Cold	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Investigations Creatinine increased	13.3% 2/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Nervous system disorders Vasovagal reaction	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Reproductive system and breast disorders Testicular pain	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
Social circumstances Lightheaded	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	14.3% 1/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks
General disorders Transient Dizziness	6.7% 1/15 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	12.5% 1/8 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks	0.00% 0/7 • From informed consent to 30 days after the cessation of treatment, an average of about 24 weeks