A Study of Benralizumab in Patients With Eosinophilic Esophagitis
Condition: Eosinophilic Esophagitis
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Intervention: Benralizumab; Matching placebo
Intervention description: Solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume; Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume
Intervention MeSH terms: Benralizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 211.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Eosinophilic Esophagitis; EoE; Benralizumab

Summary:

      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.
    

Eligibility 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.

          -  Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization):

               1. 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

               2. 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 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 12 weeks after last dose if IP.

        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 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.