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
Conditions
Interventions
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:
Sponsors
Sanofi-aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
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 with a physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 for =12 months treated with low, medium or high dose ICS and a second controller (ie, LABA), a third controller is allowed but not mandatory. The dose regimen should be stable for at least 1 month before Visit 1 (screening visit) and during the screening and run-in period. -Pre-bronchodilator FEV1 =85% of predicted normal at Visit 1 (screening visit) and Visit 2, prior to randomization. -Asthma Control Questionnaire 5-question version (ACQ-5) score =1.5 at Visits 1 and 2. -Treatment with intranasal mometasone =200 µg QD (or equivalent of another INCS) for 1 month prior to Visit 1 and during the run-in period (for CRSwNP). -Eligibility as per omalizumab drug-dosing table (serum IgE level =30 to =1500 IU/mL and body weight =30 to =150 kg) and ability to be dosed per the dosing table. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: - Participants who have undergone any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1. - Participants who have had a sino-nasal surgery changing the lateral wall structure of the nose, making impossible the evaluation of NPS. - Participants with conditions/concomitant diseases making them non evaluable at Visit 1 or for the primary efficacy endpoint such as: Antrochoanal polyps, Nasal septal deviation that would occlude at least one nostril, Acute sinusitis, nasal infection, or upper respiratory infection. - Severe asthma exacerbation requiring treatment with SCS in the last 4 weeks prior to Visit 1 and during screening. - Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the participant’s participation in the study - Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period. - History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit). - Known or suspected immunodeficiency, including history of invasive opportunistic infections - Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin. - History of systemic hypersensitivity or anaphylaxis to dupilumab and omalizumab, including any excipient - Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell;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 realted 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;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.;Timepoint(s) of evaluation of this end point: 1, 2 - Baseline to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Belgium, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactDirection des Opérations Cliniques
Sanofi-aventis France
Outcome results
None listed