Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis

Inclusion Criteria

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in protocol.
• Provision of signed and dated, written informed consent form (ICF) prior to any mandatory study specific procedures, sampling, and analyses and according to international guidelines and/or applicable European Union (EU) guidelines.
• Provision of signed and dated written genetic informed consent in patients that agree to participate in the genetic sampling, prior to collection of sample for genetic analysis.
• Female or male patients aged 18 to 75 years inclusive, at the time of signing the ICF.
• Patients with bilateral sinonasal polyposis that, despite treatment with a stable dose of intranasal corticosteroids (INCS) for at least 4 weeks prior to V1, in addition to history of treatment with systemic (SCS -oral, parenteral) or prior surgery for nasal polyposis (NP), have severity consistent with a need for surgery as described by:
• A minimum total Nasal Polyp Score (NPS) of 5 out of a maximum score of 8 (with a unilateral score of at least 2 for each nostril) at V1, and continuously maintained at V2 to meet the randomization criterion, as determined by the study Imaging Core Lab;
• Ongoing symptoms for at least 12 weeks prior to V1;
• Patient-reported moderate to severe nasal blockage score (NBS) 2 or 3 over the 2-weeks prior to V1 (2-week recall assessment of symptoms, scores 0-none to 3-severe).
• SNOT-22 total score ≥ 30 at enrolment.

Patient must meet the following criteria (points 7-10) at the randomization visit:

• At least 8 days of evaluable daily diary data in the 14-day period prior to randomization (baseline bi-weekly mean score collected from study Day -13 to study Day 0).
• At randomization, a bi-weekly mean NBS ≥ 1.5.
• SNOT-22 total score ≥ 30 at randomization.
• At least 70% compliance with INCS during the run-in period based on daily diary.
• Patients with a minimum weight of 40kg.
• Negative serum pregnancy test result and a negative urine pregnancy test at randomization for female patients of childbearing potential.
• Women of childbearing potential (WOCBP) must use an effective form of birth control as defined in the Clinical Study Protocol (CSP).
• Male subjects who are sexually active must be surgically sterile at least one year prior to Visit 1 or must use an adequate method of contraception (condom or condom with spermicide depending on local regulations) from the first dose of IP until 16 weeks after their last dose. Men with a partner or partners who is (are) not of childbearing potential are exempt of these requirements

Exclusion Criteria

• Patients who have undergone any nasal and/or sinus surgery within 3 months prior to V1.
• Patients with conditions or concomitant disease that makes them non evaluable for the co-primary efficacy endpoint such as:
• Unilateral antrochoanal polyps;
• Nasal septal deviation that occludes at least one nostril;
• Acute sinusitis, nasal infection, or upper respiratory infection at screening or in the 2 weeks before screening;
• Current rhinitis medicamentosa;
• Allergic fungal rhinosinusitis (AFRS) or Allergic fungal sinusitis (AFS);
• Nasal cavity tumors.
• Clinically important comorbidities that could confound interpretation of clinical efficacy results including, but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, primary ciliary dyskinesia, eosinophilic diseases other than asthma (e.g. allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangitis [Churg-Strauss syndrome], hypereosinophilic syndromes), granulomatosis with polyangitis (Wegener's granulomatosis), Young's syndrome, etc.
• Any disorder, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major