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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Benralizumab (Anti-IL5RA) in Subjects With Eosinophilic Gastritis.
Primary Objective:
To assess the efficacy of repeat subcutaneous (SC) doses of benralizumab, compared with placebo, to reduce eosinophilic inflammation in the gastrointestinal tract of patients with Eosinophilic Gastritis
Secondary Objectives:
To assess changes in endoscopic score, histological features, blood and biopsy eosinophil counts, clinical symptoms, and gastric tissue transcriptome before and after treatment with benralizumab.
26 subjects are planned to be enrolled into the study at Cincinnati Children's Hospital Medical Center. Qualifying Subjects will receive subcutaneous injections every 4 weeks (3 total) of benralizumab/Placebo, followed by optional Open Label Extension periods.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benralizumab | Experimental | Subcutaneous dose of 30 mg of Benralizumab every 4 weeks |
|
| Placebo | Placebo Comparator | Subcutaneous dose of Placebo every 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Biological | Benralizumab (anti-IL5Ra) will be injected every 4 weeks in doses of 30 mg (total of 3 injections) in subjects with active Eosinophilic Gastritis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Patients in Histological Remission (<30 Eos/Hpf) | 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). | 12 weeks after start of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Gastric Endoscopic Score (Lanza) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc E Rothenberg, MD, PhD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37336228 | Derived | Kliewer KL, Murray-Petzold C, Collins MH, Abonia JP, Bolton SM, DiTommaso LA, Martin LJ, Zhang X, Mukkada VA, Putnam PE, Kellner ES, Devonshire AL, Schwartz JT, Kunnathur VA, Rosenberg CE, Lyles JL, Shoda T, Klion AD, Rothenberg ME. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):803-815. doi: 10.1016/S2468-1253(23)00145-0. Epub 2023 Jun 16. |
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34 participants screened, 8 excluded (8 did not meet inclusion criteria), and 26 randomized
Participants were recruited from an eosinophilic disorder specialty clinic in the US between April 2018 and January 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Benralizumab | Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 doses) |
| BG001 | Placebo | Subcutaneous dose of Placebo every 4 weeks (total of 3 doses) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent of Patients in Histological Remission (<30 Eos/Hpf) | 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). | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Number | percentage of participants | 12 weeks after start of treatment |
|
From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Benralizumab | Subcutaneous dose of 30 mg of Benralizumab every 4 weeks (total of 3 doses) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marc E. Rothenberg, MD, PhD | Cincinnati Children's Hospital Medical Center | 513-636-7177 | marc.rothenberg@cchmc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 3, 2020 | Jun 18, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C535952 | Eosinophilic enteropathy |
| D005759 | Gastroenteritis |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C571386 | benralizumab |
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Participants will receive doses of drug or placebo. Optional open label extensions available following the double blind period.
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Participant/care providers, investigators, and outcome assessor (pathology) were blinded to assignment. Randomization performed by external investigational pharmacy staff (dispenses the drug/placebo).
|
| Placebo | Biological | Placebo will be injected every 4 weeks (total of 3 injections) as a comparator to Benralizumab in subjects with active Eosinophilic Gastritis. |
|
| 12 weeks after start of treatment |
| Change in Gastric Histology Score | 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. | 12 weeks after start of treatment |
| Change in Blood Eosinophil Count | 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. | 12 weeks after start of treatment |
| Change in Eosinophilic Gastritis Diagnostic Panel | 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). | 12 weeks after start of treatment |
| Change in Gastric Peak Eosinophil Count | 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. | 12 weeks after starting treatment |
| Change in Clinical Symptoms | 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. | 12 weeks after start of treatment |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Gastric Peak Eosinophil Count | Maximum eosinophil count (eosinophils per high power field) in gastric biopsies | Median | Inter-Quartile Range | eosinophils per high power field |
|
| Gastric Histology Score | Gastric histology score quantifies inflammatory and structural histologic features. Total score is the sum of features scores divided by the maximum possible score. 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. Scores range from 0 - 1. Higher scores indicate more severe abnormalities. | Median | Inter-Quartile Range | score on a scale |
|
| Gastric Endoscopy Score (Lanza) | The gastric endoscopy 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. Higher scores indicate more severe endoscopic findings. | Median | Inter-Quartile Range | score on a scale |
|
| Blood Eosinophil Count | Blood absolute eosinophil counts (cell per microliter) | Median | Inter-Quartile Range | cells per microliter |
|
| SODA Pain Intensity | The symptom of dyspepsia (SODA) questionnaire captures symptoms associated with gastric dyspepsia including symptoms associated with "pain" . Scores range from 0 to 47 for pain. Higher scores indicate more frequent and/or severe symptoms for pain. | Median | Inter-Quartile Range | score on a scale |
|
| SODA Non-Pain Symptoms | The symptom of dyspepsia (SODA) questionnaire captures symptoms associated with gastric dyspepsia including symptoms associated with "non-pain" . The scores range from 0 to 35 for non-pain. Higher scores indicate more frequent and/or severe symptoms. | Median | Inter-Quartile Range | score on a scale |
|
| SODA Satisfaction | The symptom of dyspepsia (SODA) questionnaire captures general satisfaction associated with present symptoms. The scores range 0 to 23. Higher scores indicate greater Satisfaction. | Median | Inter-Quartile Range | score on a scale |
|
| EG Diagnostic Panel | The transcriptomic signature of gastric biopsy samples was obtained using real-time polymerase chain reaction amplification on the Eosinophilic gastritis diagnostic panel (EGDP) comprising a set of 48 gastric transcripts. The EGDP value was calculated by summing the delta CT (threshold cycle) values of the most highly dysregulated genes. Higher values indicate normalization of the transcriptome. | Biopsies for gene expression analysis were not collected or failed to yield quality RNA for some subjects | Mean | Standard Deviation | delta threshold cycle |
|
|
|
|
| Secondary | Change in Gastric Endoscopic Score (Lanza) | 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. | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Median | Inter-Quartile Range | score on a scale | 12 weeks after start of treatment |
|
|
|
|
| Secondary | Change in Gastric Histology Score | 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. | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Median | Inter-Quartile Range | score on a scale | 12 weeks after start of treatment |
|
|
|
|
| Secondary | Change in Blood Eosinophil Count | 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. | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Median | Inter-Quartile Range | cells per microliter | 12 weeks after start of treatment |
|
|
|
|
| Secondary | Change in Eosinophilic Gastritis Diagnostic Panel | 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). | Includes participants with pre and post-treatment samples | Posted | Mean | Standard Deviation | delta threshold cycle | 12 weeks after start of treatment |
|
|
|
|
| Secondary | Change in Gastric Peak Eosinophil Count | 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. | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Median | Inter-Quartile Range | eosinophils per high power field | 12 weeks after starting treatment |
|
|
|
|
| Secondary | Change in Clinical Symptoms | 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. | Intent to treat analysis including participants who had at least one clinical observation post randomization. | Posted | Median | Inter-Quartile Range | score on a scale | 12 weeks after start of treatment |
|
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 11 |
| 13 |
| EG001 | Placebo | Subcutaneous dose of Placebo every 4 weeks (total of 3 doses) | 0 | 13 | 0 | 13 | 8 | 13 |
| Abdominal Pain | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Belching | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Bloating | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Hematochezia | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Bacterial overgrowth | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Chills | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Lymphadenopathy | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Sore Throat | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Weight loss | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Flu-like Symptoms | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Strep Throat | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Vaginal infection | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Insomnia | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Parasthesia | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Sensitive skin | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Satisfaction |
|
| 0.34 |
| Other |
| Satisfaction score comparison | Kruskal-Wallis | 0.66 | Other |