Eosinophilic Gastritis, Eosinophilic Gastroenteritis
Conditions
Keywords
Benralizumab, Eosinophilic Gastritis, Gastroenteritis, Intestinal Diseases, Stomach Diseases, Gastrointestinal Diseases, Digestive System Diseases
Brief summary
This is a 3-part study. Part A is randomized, double-blinded, placebo-controlled and includes patients with eosinophilic gastritis and/or duodenal-only disease. After completing Part A, participants can continue to Part C - open-label benralizumab treatment period. Following the decision to close enrollment, patients in both Part A and Part C will be given the option to proceed to 6-months of open-label benralizumab treatment in Part D.
Interventions
BIOLOGICALBenralizumab
Benralizumab is a humanized, afucosylated, monoclonal antibody that binds specifically to the IL-5Rα on the target cell and thus directly depletes eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab has been widely approved for treatment of asthma.
BIOLOGICALPlacebo
Placebo will be injected as a comparator to injection with Benralizumab to examine effect on both the signs and symptoms of EG/EGE and the underlying eosinophilic inflammation, with dual primary outcome variables
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a parallel-group efficacy and safety study with 2 arms that are participant and investigator blinded, with an open-label extension.
Eligibility
Sex/Gender
ALL
Age
12 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Aged \>= 12 years of age at the time of signing the ICF or informed consent or assent form. * Confirmed diagnosis of EG/EGE for at least 3 months prior to screening. * Baseline Eosinophilic gastritis, with or without duodenitis, or eosinophilic duodenitis alone confirmed by biopsy with a gastric count of ≥30 eosinophils/hpf in at least 5 hpfs and/or duodenal eosinophil count ≥30 eosinophils/hpf in at least 3 hpfs without any other cause for the gastrointestinal eosinophilia. * Symptoms including at least moderate abdominal pain, nausea, bloating, early satiety, and/or loss of appetite * Must be adherent to daily PRO assessments including at least 8 of 14 symptom assessments in the 14 days prior to randomization * If on background medications for EG/EGE, the medications should be stable at least 4 weeks prior to the run-in period. * Willing and able to comply with all study procedures and visit schedule including follow-up visits * Women of childbearing potential must agree to use a highly effective form of birth control (confirmed by the Investigator) from randomization throughout the study duration and within 12 weeks after last dose if IP.
Exclusion criteria
* Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease. * Hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis. * Current malignancy, or history of malignancy, except for patients who have had basal cell, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date of informed consent. * History of anaphylaxis to any biologic therapy or vaccine. * Current active liver disease. * Helminth parasitic infection diagnosed within 24 weeks prior to the date informed that has not been treated with or has failed to respond to standard of care therapy. * Known immunodeficiency disorder including testing positive for HIV. * Concomitant use of immunosuppressive medication. * Receipt of live attenuated vaccines 30 days prior to date of informed consent or assent. * Receipt of inactive vaccines within 7 days of informed consent or assent. * Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group from 6 weeks prior to start of the run-in period and unable or unwilling to remain on a stable diet until the completion of Part A and C. * Currently pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With a Histologic Response at Week 24 | at week 24 | the proportion of patients achieving a histological response at Week 24, is defined as below: * 6 eosinophils/hpf in the stomach for the patients with only gastric disease at baseline. * 6 eosinophils/hpf in the stomach and ≤15 eosinophils/hpf in the duodenum for the patients with gastric + duodenal disease at baseline. * 15 eosinophils/hpf in the duodenum for the patients with only duodenal disease at baseline. |
| Change From Baseline in SAGED Score at Week 24 | at week 24 | The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) instrument was developed to measure gastrointestinal symptoms in participants diagnosed with EG/EGE. It is a daily diary completed by participants each evening from screening until week 76 to record symptoms during the past 24 hours. Severity for each concept is assessed using an 11-point numerical rating scale (0 = 'none' and 10 = 'worst imaginable'). The total SAGED score (range 0-50) is calculated as a 14-day mean of the sum of individual severity items of abdominal pain, nausea, bloating, early satiety and loss of appetite daily. Higher scores indicate greater symptom severity. Three additional items are collected that aren't part of the total SAGED score and are considered separately: severity of vomiting, severity of diarrhoea and frequency of vomiting. Change in SAGED score at week 24 is the week 24 score (study days 155 to 168) minus the baseline score (study days -14 to -1). |
Countries
Brazil, Italy, Japan, Netherlands, Poland, Spain, Ukraine, United States, Vietnam
Participant flow
Recruitment details
A total of 34 participants were screened. Of those, 12 participants were randomised to either the treatment (6 participants) or placebo (participants) arms of the double-blinded treatment period.
Pre-assignment details
All participants complete a 4-week to 8-week run-in period during which inclusion/exclusion criteria was assessed.
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab Patients received benralizumab 30mg every 4 weeks for the 24 weeks treatment period | 6 |
| Placebo Patients received matching Placebo every 4 weeks for the 24 weeks treatment period | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open Label Extension | Subjects who discontinued treatment with study drug in OLE but completed study follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Benralizumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 6 / 6 | 3 / 6 | 6 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 9 |
Outcome results
Primary
Change From Baseline in SAGED Score at Week 24
The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) instrument was developed to measure gastrointestinal symptoms in participants diagnosed with EG/EGE. It is a daily diary completed by participants each evening from screening until week 76 to record symptoms during the past 24 hours. Severity for each concept is assessed using an 11-point numerical rating scale (0 = 'none' and 10 = 'worst imaginable'). The total SAGED score (range 0-50) is calculated as a 14-day mean of the sum of individual severity items of abdominal pain, nausea, bloating, early satiety and loss of appetite daily. Higher scores indicate greater symptom severity. Three additional items are collected that aren't part of the total SAGED score and are considered separately: severity of vomiting, severity of diarrhoea and frequency of vomiting. Change in SAGED score at week 24 is the week 24 score (study days 155 to 168) minus the baseline score (study days -14 to -1).
Time frame: at week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab | Change From Baseline in SAGED Score at Week 24 | -9.59 score | Standard Error 7.26 |
| Placebo | Change From Baseline in SAGED Score at Week 24 | -13.69 score | Standard Error 4.37 |
Primary
Proportion of Patients With a Histologic Response at Week 24
the proportion of patients achieving a histological response at Week 24, is defined as below: * 6 eosinophils/hpf in the stomach for the patients with only gastric disease at baseline. * 6 eosinophils/hpf in the stomach and ≤15 eosinophils/hpf in the duodenum for the patients with gastric + duodenal disease at baseline. * 15 eosinophils/hpf in the duodenum for the patients with only duodenal disease at baseline.
Time frame: at week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benralizumab | Proportion of Patients With a Histologic Response at Week 24 | 5 Participants |
| Placebo | Proportion of Patients With a Histologic Response at Week 24 | 0 Participants |