Ensayos clínicos

Inclusion Criteria:

• Informed consent or assent (if applicable).
• Provision of signed and dated, written informed consent form or assent form (if applicable) prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written Genetic informed consent prior to collection of sample for genetic analysis for adult patients.
• 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 (run-in period) and Visit 2 (randomization):
  • A patient reported average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to the run-in period; AND
  • At least 2 days with an episode of dysphagia (Daily DSQ ≥2) per week between Visit 1 and the Visit 2 (randomization).
• Must be adherent to daily diary assessments:
  • Must complete 70% of daily diaries between Visit 1 and Visit 2; AND
  • 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 prior to the run-in period and there is agreement not to change type of background medication or dosage for the first 52 weeks of the study unless medically indicated. Patients on PPI therapy must report a stable dose for at least 8 weeks prior to the run-in period..
• Body weight of at least 35 kg.
• Negative serum pregnancy test for female patients of childbearing potential at Visit 1 (enrollment).
• Women of childbearing potential (WOCBP) 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. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation- oral, intravaginal, or transdermal;
  • Progestogen-only hormonal contraception associated with inhibition of ovulationoral, injectable, or implantable;
  • Intrauterine device (IUD);
  • Intrauterine hormone-releasing system (IUS);
  • Bilateral tubal occlusion;
  • Sexual abstinence; i.e., refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient);'
  • Vasectomized sexual partner (provided that partner is the sole sexual partner of the WOCBP study patient and that the vasectomized partner has received medical assessment of the surgical success).
• Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for ≥ 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:
  • Women < 50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.  Until FSH is documented to be within menopausal range, treat the patient as WOCBP;
  • Women ≥ 50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:

• As judged by the Investigator, any evidence of a medical illness which, in the Investigator’s opinion, makes it undesirable for the patient to participate in the study.
• 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.
• Any clinical significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during run-in period which, in the opinion of the Investigator, may put the patient at risk, because of his/her participation in the study, or may influence the results of the study, or the patients’ ability to complete entire duration of the study.
• Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period.
• Ise of a feeding tube, or 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, except for:
  • Patients who have had basal cell carcinoma, 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 informed consent, and assent when applicable was obtained.
• Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained.
• 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. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis.
• 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.
• Transient increase of AST/ALT level that resolves by the time of randomization is acceptable if in the Investigator’s opinion the patient does not have an active liver disease and meets other eligibility criteria.
• 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 (including but not limited to:
• methotrexate, troleandomycin, cyclosporine, azathioprine, and systemic corticosteroids.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent or assent (if applicable) is obtained.
• Receipt of live attenuated vaccines 30 days prior to date of informed consent or assent (if applicable).
• Receipt of any marketed or investigational biologic (monoclonal or polyclonal antibody) within 4 months or 5 half-lives prior to the date informed consent or assent (if applicable), is obtained, whichever is longer, and during the study period.
• Previous participation in a benralizumab clinical study.
• Known history of allergy or reaction to any component of the IP formulation.
• Receipt of any investigational drug within 30 days or 5 half-lives prior to randomization, whichever is longer.
• 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 the run-in period.
• For women only: Currently pregnant, breastfeeding, or lactating women.
• A serum pregnancy test will be done for women of childbearing potential at screening and a urine pregnancy test must be performed for women of childbearing potential at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the patient should be excluded.