Eosinophilic Esophagitis (EoE) MedDRA version: 20.1 Level: LLT Classification code 10064220 Term: Eosinophilic esophagitis System Organ Class: 100000004856
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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 (documented diagnosis defined as an esophageal count of =15 eos/hpf on at least 1 esophageal level) and confirmed diagnosis by a centrally-read esophageal biopsy for the purposes of this study (confirmed diagnosis defined as an esophageal count of =15 eos/hpf at 2 or more esophageal levels). Two to 4 biopsies should be obtained from both the proximal and distal esophagus. Biopsies can be taken from the mid-esophagus for additional evaluation. -Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization): (a) A patient reported average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND (b) An average of at least 2 days with an episode of dysphagia (Daily DSQ =2) per week between Visit 1 and the 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. -Must be adherent to daily diary assessments: (a) Must complete 70% of daily diaries between Visit 1 and Visit 2; AND (b) Must have completed at least 8 of 14 daily diaries in the 14 days 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. -Body weight of at least 35 kg. -Negative serum pregnancy test for female patients of childbearing potential at Visit1. -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 16 weeks after last dose if IP. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -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 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 screening 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 re-introduction of a previously eliminated food group in the 6 weeks prior to start of and during the run-in period. -Currently pregnant, breastfeeding, or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of benralizumab Dose Regimen 1 on histologic signs and symptoms of EoE in patients with symptomatic and histologically active EoE.;Secondary Objective: DB treatment period: -To evaluate the effect of benralizumab Dose Regimen 1 on clinical features of EoE and disease activity. -To evaluate the effect of benralizumab Dose Regimen 1 on patient reported QOL measures. -To evaluate the effect of benralizumab Dose Regimen 1 on healthcare resource utilization due to EoE. -To evaluate the effect of benralizumab Dose Regimen 1 on patient reported measures of disease severity and health status. -To assess the PK and immunogenicity of benralizumab Dose Regimen 1 in patients with EoE. -To assess the safety and tolerability of benralizumab Dose Regimen 1 in patients with EoE.;Primary end point(s): Dual-primary Endpoints: -Proportion of patients with a histologic response at Week 24, defined as a peak esophageal intraepithelial eosinophil count = 6 eos/hpf - Changes from baseline in DSQ score at Week 24;Timepoint(s) of evaluation of this end point: Both at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study Objectives for the DB treatment period: -Key secondary endpoint: Changes from baseline in centrally-read EoE EREFS at Week 24 -Centrally-read biopsies for additional histopathology and tissue eosinophil counts, including EoE-HSS, at Week 24 -Dysphagia-free days as captured by the DSQ -Frequency of dysphagia episodes as captured by the EoE-3D -Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24 -Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24 -Changes from baseline in EoE-QoL-A at Week 24 -SF-36 v2 Health Survey at Week 24 - Percent of patients with relevant concomitant procedures and healthcare resource utilization during the study through Week 24 -PGI-S at Week 24 - PGI-C at Week 24 -Serum benralizumab concentration -ADA and nAb -Safety and tolerability will be evaluated in terms of AEs, Vital signs, and Clinical laboratory values;Timepoint(s) of evaluation of this end point: Varies depending on the endpoint/objective | — |
Countries
Canada, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZenecaAB
Outcome results
None listed