A randomized, double-blind, head-to-head comparison of dupilumab versus omalizumab in severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and comorbid asthma patients - EVEREST

INTERVENTION: Product Name: Dupilumab Product Code: SAR231893 Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Dupilumab Current Sponsor code: SAR231893 Other descriptive name: REGN668 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use Trade Name: Xolair Product Name: Omalizumab Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: OMALIZUMAB CAS Number: 242138‐07‐4 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 150‐ Trade Name: Xolair Product Name: Omalizumab Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: OMALIZUMAB CAS Number: 242138‐07‐4 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 150‐ CONDITION: Chronic rhinosinusitis with nasal polyps ; MedDRA version: 20.1 Level: PT Classification code 10080060 Term: Chronic rhinosinusitis with nasal polyps System Organ Class: 10038738 ‐ Respiratory, thoracic and mediastinal disorders Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: ‐To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell Primary end point(s): 1 ‐ Change from baseline to Week 24 in Nasal Polyp Score (NPS) ; The total nasal polyps score (NPS) is the sum of the right and left nostrils, ranging from 0 (no polyps) to 8 (large polyps causing complete obstruction).; 2 ‐ Change from baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT) ; The UPSIT score ranges from 0 to 40, with 40 being the best possible score. Secondary Objective: ‐ To evaluate the efficacy of dupilumab in improving CRSwNP symptoms at Week 24 compared to omalizumab ; ‐ To evaluate the efficacy of dupilumab in improving lung function at Week 24 compared to omalizumab; ‐ To evaluate the efficacy of dupilumab in improving CRSwNP total symptom score (TSS) at Week 24 compared to omalizumab ; ‐ To evaluate the effect of dupilumab on health related quality of life (HRQoL) at week 24 compared to omalizumab; ‐ To evaluate the efficacy of dupilumab in improving nasal peak inspiratory flow at Week 24 compared to omalizumab; ‐ To evaluate the effect of dupilumab on CRSwNP overall disease severity at Week 24 compared to omalizumab; ‐ To evaluate the effect of dupilumab on asthma control at Week 24 compared to omalizumab; ‐ To evaluate the safety of dupilumab and omalizumab Timepoint(s) of evaluation of this end point: 1, 2 ‐ Baseline to Week 24 SECONDARY OUTCOME: Secondary end point(s): 1 ‐ Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom Diary ; Loss of smell scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms'). ; 2 ‐ Change from baseline to Week 24 in the NC score of the CRSwNP Nasal Symptom Diary ; NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').; 3 ‐ Change from baseline to Week 24 in pre­bronchodilator forced expiratory volume in 1 second (FEV1) ; Pre‐broncodilator forced expiratory volume in 1 second (volume of air in liters) ; 4 ‐ Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom Diary ; TSS ranges from 0 to 9. Higher scores on the TSS indicate greater symptom severity; 5 ‐ Change from baseline to Week 24 in 22‐Item Sino­nasal Outcome Test (SNOT‐22) ; SNOT‐22 is a patient‐reported outcome (PRO) questionnaire. Score ranges from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.; 6 ‐ Change from baseline to Week 24 in SNOT‐22 nasal domain score ; SNOT‐22 is a patient‐reported outcome (PRO) questionnaire. Nasal domain score ranges from 0‐40 with high score representing higher disease burden. ; 7 ‐ Change from baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF) ; Nasal Peak Inspiratory flow (nasal flow in liter per minute); 8 ‐ Change from baseline to Week 24 in rhinosinusitis VAS ; Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom. ; 9 ‐ Change from baseline to Week 24 in 7‐item Asthma Control Questionnaire (ACQ‐7) ; Asthma control with 6 questions plus FEV1 measure. Score ranges from 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.; 10 ‐ Incidence of treatment‐emergent adverse events (TEAEs) and serious adverse events (SAEs) ; Incidence of treatment‐emergent adverse events (TEAEs) and serious adverse events (SAEs); 11 ‐ Incidence of adverse events of special interest (AESIs) ; Incidence of adverse events of special interest (AESIs) Timepoint(s) of evaluation of this end point: 1, 2, 3, 4, 5, 6, 7, 8, 9 ‐ Baseline to Week 24; 10, 11 ‐ Baseline to Week 36 INCLUSION CRITERIA: ‐Participant must be at least 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent. ‐Participants with bilateral sino‐nasal polyposis, that despite prior treatment with SCS anytime within the past 2 years; and/or medical contraindication/intolerance to SCS; and/or prior surgery for NP have: ‐‐ An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) at visit 1; AND ‐‐ Ongoing symptoms of Nasal congestion/blockade/obstruction and loss of smell for at least 8 weeks before screening (Visit 1), AND ‐‐ Nasal congestion/blockade/obstruction and a weekly average severity greater than 1 at randomization (Visit 2) AND ‐‐ loss of smell symptom severity score 2 or 3 at screening (Visit 1) and a weekly average severity of greater than 1 at time of randomization (Visit 2). ‐Participants