Trial Outcomes & Findings for Benralizumab for Eosinophilic Gastritis (BEGS) (NCT NCT03473977)

Last Updated: 2022-02-03

Results Overview

Percent of patients in histologic remission in drug versus placebo groups. Remission is defined as gastric peak eosinophil count \< 30 eosinophils per high powered field (eos/hpf).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

26 participants

Primary outcome timeframe

12 weeks after start of treatment

Results posted on

2022-02-03

Participant Flow

Participants were recruited from an eosinophilic disorder specialty clinic in the US between April 2018 and January 2020.

34 participants screened, 8 excluded (8 did not meet inclusion criteria), and 26 randomized

Participant milestones

Participant milestones
Measure	Benralizumab Subcutaneous dose of 30 mg of Benralizumab every 4 weeks Benralizumab: Benralizumab (anti-IL5Ra) will be injected in doses of 30 mg every 4 weeks (3 times) in subjects with active Eosinophilic Gastritis.	Placebo Subcutaneous dose of Placebo every 4 weeks Placebo: Placebo will be injected every 4 weeks (3 times) as a comparator to Benralizumab in subjects with active Eosinophilic Gastritis.
Overall Study STARTED	13	13
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Biopsies for gene expression analysis were not collected or failed to yield quality RNA for some subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 doses)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 doses)	Total n=26 Participants Total of all reporting groups
Age, Continuous	14.9 years STANDARD_DEVIATION 2.0 • n=13 Participants	24.1 years STANDARD_DEVIATION 7.9 • n=13 Participants	19.5 years STANDARD_DEVIATION 7.3 • n=26 Participants
Sex: Female, Male Female	4 Participants n=13 Participants	3 Participants n=13 Participants	7 Participants n=26 Participants
Sex: Female, Male Male	9 Participants n=13 Participants	10 Participants n=13 Participants	19 Participants n=26 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=13 Participants	1 Participants n=13 Participants	2 Participants n=26 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=13 Participants	12 Participants n=13 Participants	24 Participants n=26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Asian	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Black or African American	1 Participants n=13 Participants	0 Participants n=13 Participants	1 Participants n=26 Participants
Race (NIH/OMB) White	12 Participants n=13 Participants	13 Participants n=13 Participants	25 Participants n=26 Participants
Race (NIH/OMB) More than one race	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=13 Participants	0 Participants n=26 Participants
Region of Enrollment United States	13 participants n=13 Participants	13 participants n=13 Participants	26 participants n=26 Participants
Gastric Peak Eosinophil Count	210 eosinophils per high power field n=13 Participants	147 eosinophils per high power field n=13 Participants	157 eosinophils per high power field n=26 Participants
Gastric Histology Score	0.55 score on a scale n=13 Participants	0.50 score on a scale n=13 Participants	0.50 score on a scale n=26 Participants
Gastric Endoscopy Score (Lanza)	4.0 score on a scale n=13 Participants	6.0 score on a scale n=13 Participants	5.0 score on a scale n=26 Participants
Blood Eosinophil Count	1100 cells per microliter n=13 Participants	1640 cells per microliter n=13 Participants	1350 cells per microliter n=26 Participants
SODA Pain Intensity	25 score on a scale n=13 Participants	27 score on a scale n=13 Participants	26 score on a scale n=26 Participants
SODA Non-Pain Symptoms	16 score on a scale n=13 Participants	15.5 score on a scale n=13 Participants	16 score on a scale n=26 Participants
SODA Satisfaction	10 score on a scale n=13 Participants	8 score on a scale n=13 Participants	9 score on a scale n=26 Participants
EG Diagnostic Panel	-58 delta threshold cycle STANDARD_DEVIATION 23 • n=9 Participants • Biopsies for gene expression analysis were not collected or failed to yield quality RNA for some subjects	-51 delta threshold cycle STANDARD_DEVIATION 40 • n=9 Participants • Biopsies for gene expression analysis were not collected or failed to yield quality RNA for some subjects	-55 delta threshold cycle STANDARD_DEVIATION 32 • n=18 Participants • Biopsies for gene expression analysis were not collected or failed to yield quality RNA for some subjects

PRIMARY outcome

Timeframe: 12 weeks after start of treatment

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

Percent of patients in histologic remission in drug versus placebo groups. Remission is defined as gastric peak eosinophil count \< 30 eosinophils per high powered field (eos/hpf).

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Percent of Patients in Histological Remission (<30 Eos/Hpf)	77 percentage of participants	8 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after start of treatment

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

The gastric endoscopic score (Lanza) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (granularity, nodularity, erosion/ulceration, friability, erythema). Total score is the maximum score of the five feature scores from the body, antrum, or fundus. Total scores range from 0 - 14. Change in total endoscopic reference score is defined as post-treatment score minus pre-treatment score. Changes in scores are compared between drug and Placebo. A reduction (negative change) in score indicates improvement.

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Gastric Endoscopic Score (Lanza)	-1.0 score on a scale Interval -1.0 to 0.0	0.0 score on a scale Interval -2.0 to 0.0

SECONDARY outcome

Timeframe: 12 weeks after start of treatment

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

The gastric histology score quantifies inflammatory and structural histologic abnormalities in the stomach. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Features include lamina propria eosinophil sheets, periglandular circumferential collars, eosinophils in surface epithelium, eosinophil glandulitis, eosinophil gland abscesses, eosinophils in muscularis mucosa, lamina propria fibroplasia, lamina propria smooth muscle hyperplasia, reactive epithelial changes, acute inflammatory cells, and surface erosion. Total scores range from 0 - 1. Change in gastric total histology scoring is defined as post-treatment total score minus pretreatment total score. Changes in scores are compared between drug and placebo. A reduction (negative change) in score indicates improvement.

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Gastric Histology Score	-0.33 score on a scale Interval -0.41 to -0.27	-0.04 score on a scale Interval -0.1 to 0.05

SECONDARY outcome

Timeframe: 12 weeks after start of treatment

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

Change in absolute eosinophil counts (cells per microliter) is defined as post treatment counts minus pre-treatment counts. Changes in counts are compared between drug and Placebo. A decrease in count is expected due to the effects of the drug.

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Blood Eosinophil Count	-1060 cells per microliter Interval -1740.0 to -830.0	-160 cells per microliter Interval -710.0 to 120.0

SECONDARY outcome

Timeframe: 12 weeks after start of treatment

Population: Includes participants with pre and post-treatment samples

The transcriptomic signature of gastric biopsy samples was obtained using real-time polymerase chain reaction amplification on the EG diagnostic panel (EGDP) comprising a set of 48 gastric transcripts. The EGDP value was calculated by summing delta CT (threshold cycle) values of the most highly dysregulated genes. Change is defined as post treatment value minus pre-treatment value. An increase (positive change) indicates improvement (normalization of gene expression).

Outcome measures

Outcome measures
Measure	Benralizumab n=9 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=9 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Eosinophilic Gastritis Diagnostic Panel	29 delta threshold cycle Standard Deviation 31	-12 delta threshold cycle Standard Deviation 23

SECONDARY outcome

Timeframe: 12 weeks after starting treatment

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

Change in gastric peak eosinophil count is defined as post-treatment peak count minus pre-treatment peak count. Changes in peak count are compared between Drug and Placebo. A reduction (negative change) in peak count indicates improvement.

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Gastric Peak Eosinophil Count	-132 eosinophils per high power field Interval -196.0 to -82.0	-29 eosinophils per high power field Interval -89.0 to 0.0

SECONDARY outcome

Timeframe: 12 weeks after start of treatment

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

The symptom of dyspepsia (SODA) questionnaire captures symptoms associated with gastric dyspepsia including symptoms associated with "pain" and "non-pain" as well as general "satisfaction" with present symptoms. The scores range from 0 to 47 for pain; 0 to 35 for non-pain, and 0 to 23 for satisfaction. Higher scores indicate more frequent and/or severe symptoms for pain and non-pain. Higher scores indicate greater Satisfaction. Change in score is defined as post-treatment total score minus pre-treatment total score. A reduction (negative change) indicates improvement in pain and non-pain. An increase (positive change) indicates improvement in satisfaction.

Outcome measures

Outcome measures
Measure	Benralizumab n=13 Participants Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 injections)	Placebo n=13 Participants Subcutaneous dose of Placebo every 4 weeks (total of 3 injections)
Change in Clinical Symptoms Pain score	-3.0 score on a scale Interval -9.0 to 0.0	-2.0 score on a scale Interval -6.0 to 0.0
Change in Clinical Symptoms Non-pain score	-2.0 score on a scale Interval -4.0 to 0.0	-1.0 score on a scale Interval -3.0 to 1.0
Change in Clinical Symptoms Satisfaction	1.0 score on a scale Interval 0.0 to 5.0	2.5 score on a scale Interval 0.0 to 5.0

Adverse Events

Benralizumab

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 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

Measure	Benralizumab n=13 participants at risk Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 doses)	Placebo n=13 participants at risk Subcutaneous dose of Placebo every 4 weeks (total of 3 doses)
Blood and lymphatic system disorders Anemia	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Abdominal Pain	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Belching	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Bloating	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Constipation	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Diarrhea	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Flatulence	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Hematochezia	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Nausea	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Bacterial overgrowth	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Gastrointestinal disorders Vomiting	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	23.1% 3/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Chills	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Fatigue	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Fever	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Lymphadenopathy	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Sore Throat	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
General disorders Weight loss	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Infections and infestations Enterocolitis infectious	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Infections and infestations Flu-like Symptoms	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Infections and infestations Strep Throat	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Infections and infestations Vaginal infection	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Metabolism and nutrition disorders Anorexia	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Dizziness	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Headache	46.2% 6/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	15.4% 2/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Insomnia	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Migraine	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Parasthesia	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Somnolence	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Nervous system disorders Syncope	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Psychiatric disorders Anxiety	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
Skin and subcutaneous tissue disorders Sensitive skin	7.7% 1/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.	0.00% 0/13 • From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.