A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 211
- 试验地点
- 79
- 主要终点
- Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.
研究概览
简要总结
The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week open-label treatment period). It is proposed that benralizumab will deplete eosinophils from GI tissue(s), improve the symptoms of dysphagia, and improve endoscopy scores as well as other markers of disease activity. Upon completion of the initial 52-week treatment period, patients will be offered an additional Open Label Extension period of at least 1 year, with benralizumab treatment and ongoing study assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form.
- •Documented previous diagnosis of EoE by endoscopy.
- •Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization):
- •A patient reported an average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND
- •An average of at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) between Visit 1 and Visit 2, and at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) in each of the 2 weeks immediately prior to randomization
- •May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to the screening and there is agreement not to change type of background medication or dosage during the run-in period and for the first 52 weeks of the study unless a change is medically indicated.
- •Negative serum pregnancy test for female patients of childbearing potential at Visit
- •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.
排除标准
- •Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease.
- •Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period.
- •Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery that would impact the assessments for EoE
- •Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period.
- •Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count >1500 eos/μL.
- •EGPA vasculitis.
- •Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy.
- •Current malignancy, or history of malignancy with some specific exceptions.
- •History of anaphylaxis to any biologic therapy or vaccine.
- •Current active liver disease:
- •Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period.
- •Helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent or assent (if applicable) is obtained that has not been treated with or has failed to respond to standard of care therapy.
- •History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
- •Concomitant use of immunosuppressive medication.
- •Initiation or change of a food-elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to start of the run-in period.
- •Currently pregnant, breastfeeding, or lactating women.
结局指标
主要结局
Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.
时间窗: Week 24, Week 52
Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count \<= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders. The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.
Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)
时间窗: Week 24, Week 52
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing. The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).
次要结局
- Percent Change From Baseline in Tissue Eosinophils(Week 24, Week 52)
- Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24(Week 24)
- Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24(Week 24)
- Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)(Week 24, Week 52)
- Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)(Week 24, Week 52)
- Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24(Week 24)
- Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24(Week 24)
- Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24(Week 24)
- Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)(Week 24, Week 52)
- Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24(Week 24)
- Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)(Week 24, Week 52)
- Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52(Week 52)
- Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24(Week 24)
- Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52(Week 52)
- Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24(Week 24)
- Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24(Week 24)
- Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.(Week 24, Week 52)
- Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52(Week 52)
- Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52(Week 52)
- Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52(Week 52)
- Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24(Week 24)
- Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52(Week 52)