Benralizumab Effect on Severe Chronic Rhinosinusitis With Eosinophilic Polyposis
Condition: Chronic Rhinosinusitis (Diagnosis); Nasal Polyps; Eosinophilia
MeSH terms: Sinusitis; Nasal Polyps; Eosinophilia
Intervention: Benralizumab; Placebo
Intervention description: 30mg Benralizumab will be delivered subcutaneously; Subcutaneous placebo injection
Intervention MeSH terms: Benralizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Benralizumab will be used in a placebo controlled randomized study to treat severe chronic
      rhinosinusitis with nasal polyps
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults aged 18-75

          -  Severe bilateral nasal polyps with average endoscopic score of at least 5

          -  Blood eosinophil count of at least 300/ul at screening

          -  At least 1000mg prednisone (or equivalent) over the previous 12 months to control
             symptoms

          -  At least one prior nasal surgical polypectomy

          -  Informed Consent: Able to give written informed consent prior to participation in the
             study, which will include the ability to comply with the requirements and restrictions
             listed in the consent form. Subjects must be able to read, comprehend, and write at a
             level sufficient to complete study related materials.

          -  Female subjects: Women of childbearing potential (WOCBP) must use an effective form of
             birth control (confirmed by the Investigator). Effective forms of birth control
             include: true sexual abstinence, a vasectomized sexual partner, Implanon, female
             sterilization by tubal occlusion, any effective Intra-uterine device (IUD)
             intrauterine device/ levonogestrel Intrauterine system (IUS), Depo-Provera(tm)
             injections, oral contraceptive, and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree
             to use effective method of birth control, as defined above, from enrolment, throughout
             the study duration and within 16 weeks after last dose of IP, and have negative serum
             pregnancy test result on Visit 0.

          -  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 visit -1 without an alternative
             medical cause. The following age-specific requirements apply:

          -  Women <50 years old would 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.

          -  Women ≥50 years old would be considered postmenopausal if they have been amenorrheic
             for 12 months or more following cessation of all exogenous hormonal treatment.

          -  All male subjects who are sexually active must agree to use an acceptable method of
             contraception (condom with or without spermicide, vasectomy) from Visit 0 until 16
             weeks after their last dose.

        Exclusion Criteria:

          -  Immunosuppression other than oral steroids in the past 3 months

          -  Allergen immunotherapy build up phase in the past 3 months

          -  Symptomatic or untreated life threatening cardiopulmonary disorders

          -  Subjects who are febrile (≥38°C; ≥100.4°F);

          -  History of cancer: Subjects 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 subject is in remission and curative therapy was completed at least 12 months
             prior to the date informed consent, and assent when applicable was obtained. Subjects
             who have had other malignancies are eligible provided that the subject is in remission
             and curative therapy was completed at least 5 years prior to the date informed
             consent, and assent when applicable, was obtained.

          -  A helminth parasitic infection diagnosed within 24 weeks prior to the date informed
             consent is obtained that has not been treated with, or has failed to respond to
             standard of care therapy.

          -  Pregnant or nursing

          -  If female and of child-bearing potential, positive pregnancy test or failure to adhere
             to acceptable method of contraception (with <1% failure rate) during the study and for
             four months after the study.

          -  Receipt of any investigational non biologic within 30 days or 5 half-lives prior to
             visit 0, whichever is longer.

          -  A history of known immunodeficiency disorder including a positive human
             immunodeficiency virus (HIV) test.

          -  Any other medical illness that precludes study involvement

          -  Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a
             positive medical history for hepatitis B or C. Subjects with a history of hepatitis B
             vaccination without history of hepatitis B are allowed to be enrolled.

          -  Patients who are currently receiving or have previously received benralizumab or any
             other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab
             etc.) within the last 4 months or 5 half-lives whichever is longer.

          -  History of anaphylaxis to any biologic therapy or vaccine.

          -  Receipt of immunoglobulin or blood products within 30 days prior to the date informed
             consent is obtained.

          -  Receipt of live attenuated vaccines within 30 days of starting the study drug.