EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients
- Conditions
- Chronic Rhinosinusitis With Nasal PolypsAsthma
- Interventions
- Registration Number
- NCT04998604
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective
-To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell
Secondary Objectives
* To evaluate the efficacy of dupilumab in improving chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms 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 safety of dupilumab and omalizumab
- Detailed Description
Study duration per participant will be 38 weeks. The study will comprise 3 periods: 28 days ± 3 days screening and run-in period; 24 weeks Randomized investigational medicinal product (IMP) intervention period; up to 12 weeks follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 320
-
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 Systemic corticosteroids (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 in the 7 days before 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 in the 7 days before randomization (Visit 2).
-
Participants with a physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 treated with low, medium or high dose inhaled corticosteroids (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.
-
Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 or 2.
-
Treatment with intranasal mometasone ≥200 μg once daily (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.
Participants are excluded from the study if any of the following criteria apply:
- 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).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab Placebo Dosing every 2 weeks (Q2W) Omalizumab Placebo Dosing Q2W or every 4 weeks (Q4W) Dupilumab Dupilumab Dosing every 2 weeks (Q2W) Omalizumab Omalizumab Dosing Q2W or every 4 weeks (Q4W)
- Primary Outcome Measures
Name Time Method Change from baseline to Week 24 in Nasal Polyp Score (NPS) Baseline to Week 24 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).
Change from baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT) Baseline to Week 24 The UPSIT score ranges from 0 to 40, with 40 being the best possible score.
- Secondary Outcome Measures
Name Time Method Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom Diary Baseline to Week 24 Loss of smell scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').
Change from baseline to Week 24 in the nasal congestion (NC) score of the CRSwNP Nasal Symptom Diary Baseline to week 24 NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').
Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom Diary Baseline to Week 24 TSS ranges from 0 to 9. Higher scores on the TSS indicate greater symptom severity.
Change from baseline to Week 24 in 22-Item Sino-nasal Outcome Test (SNOT-22) and Baseline to Week 24 SNOT-22 is a patient-reported outcome (PRO) questionnaire. Score ranges from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.
Change from baseline to Week 24 in SNOT-22 nasal domain score Baseline to Week 24 SNOT-22 is a patient-reported outcome (PRO) questionnaire. Nasal domain score ranges from 0-40 with high score representing higher disease burden.
Change from baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF) Baseline to Week 24 Nasal Peak Inspiratory flow (nasal flow in liter per minute).
Change from baseline to Week 24 in rhinosinusitis visual analogue scale (VAS) Baseline to Week 24 Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom.
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) Baseline to Week 36 Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Incidence of adverse events of special interest (AESIs) Baseline to Week 36 Incidence of adverse events of special interest (AESIs).
Trial Locations
- Locations (94)
Rush University Medical Center Site Number : 8400035
🇺🇸Chicago, Illinois, United States
University of Missouri Health Care - University Hospital Site Number : 8400016
🇺🇸Columbia, Missouri, United States
Chryaslis Clinical Research Site Number : 8400017
🇺🇸Saint George, Utah, United States
Eastern Virginia Medical School Site Number : 8400010
🇺🇸Norfolk, Virginia, United States
University of Texas Health Science Center- Site Number : 8400019
🇺🇸Houston, Texas, United States
Modena Allergy + Asthma Site Number : 8400033
🇺🇸La Jolla, California, United States
Cedars Sinai Medical Center Site Number : 8400026
🇺🇸Los Angeles, California, United States
Cleveland Clinic Foundation Site Number : 8400029
🇺🇸Cleveland, Ohio, United States
Optimed Research, LTD Site Number : 8400014
🇺🇸Columbus, Ohio, United States
Investigational Site Number : 0560001
🇧🇪Gent, Belgium
Investigational Site Number : 0560002
🇧🇪Leuven, Belgium
Investigational Site Number : 2030003
🇨🇿Ostrava - Poruba, Czechia
Investigational Site Number : 2030002
🇨🇿Pardubice, Czechia
Investigational Site Number : 2030006
🇨🇿Praha 2, Czechia
Investigational Site Number : 2030004
🇨🇿Praha 5 - Motol, Czechia
Investigational Site Number : 2080003
🇩🇰Aarhus, Denmark
Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027
🇺🇸Tampa, Florida, United States
Northwestern University Site Number : 8400001
🇺🇸Chicago, Illinois, United States
Advanced ENT and Allergy Site Number : 8400013
🇺🇸Louisville, Kentucky, United States
Essential Medical Research, LLC Site Number : 8400024
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number : 1240006
🇨🇦Ottawa, Ontario, Canada
Investigational Site Number : 1240002
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1240003
🇨🇦Quebec, Canada
Investigational Site Number : 2030012
🇨🇿Plzen, Czechia
Investigational Site Number : 2460003
🇫🇮Helsinki, Finland
Investigational Site Number : 2080001
🇩🇰Copenhagen, Denmark
Investigational Site Number : 2460002
🇫🇮Tampere, Finland
Investigational Site Number : 2500009
🇫🇷Creteil, France
Northwell Health Site Number : 8400044
🇺🇸Great Neck, New York, United States
University of Rochester Site Number : 8400015
🇺🇸Rochester, New York, United States
Dept of Otolaryngology, Head and Neck Surgery Site Number : 8400028
🇺🇸Cincinnati, Ohio, United States
Allergy, Asthma and Clinical Research Center Site Number : 8400037
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University Site Number : 8400031
🇺🇸Portland, Oregon, United States
Investigational Site Number : 0560003
🇧🇪Sint-Lambrechts-Woluwe, Belgium
Investigational Site Number : 1240004
🇨🇦London, Ontario, Canada
Investigational Site Number : 2030007
🇨🇿Benesov, Czechia
Investigational Site Number : 2030001
🇨🇿Hradec Kralove, Czechia
Investigational Site Number : 2500008
🇫🇷Kremlin Bicetre, France
Investigational Site Number : 2030010
🇨🇿Praha 10, Czechia
Investigational Site Number : 2030008
🇨🇿Praha 4, Czechia
Investigational Site Number : 2500006
🇫🇷La Roche sur Yon, France
Investigational Site Number : 2500002
🇫🇷Lille, France
Investigational Site Number : 2500004
🇫🇷Marseille, France
Investigational Site Number : 2500005
🇫🇷Montpellier, France
Investigational Site Number : 2500001
🇫🇷Nantes, France
Investigational Site Number : 2500007
🇫🇷Toulouse, France
Investigational Site Number : 2500003
🇫🇷Vandoeuvre-les-nancy, France
Investigational Site Number : 2760002
🇩🇪Berlin, Germany
Investigational Site Number : 2760004
🇩🇪Düsseldorf, Germany
Investigational Site Number : 3480007
🇭🇺Budapest, Hungary
Investigational Site Number : 3480004
🇭🇺Budapest, Hungary
Investigational Site Number : 3480005
🇭🇺Debrecen, Hungary
Investigational Site Number : 3480002
🇭🇺Pécs, Hungary
Investigational Site Number : 3800002
🇮🇹Roma, Lazio, Italy
Investigational Site Number : 6200005
🇵🇹Almada, Portugal
Investigational Site Number : 6200001
🇵🇹Matosinhos, Portugal
Investigational Site Number : 7240003
🇪🇸Jerez de la Frontera, Cádiz, Spain
Investigational Site Number : 2760006
🇩🇪Hamburg, Germany
Investigational Site Number : 2760003
🇩🇪München, Germany
Investigational Site Number : 2760001
🇩🇪Münster, Germany
Investigational Site Number : 3480006
🇭🇺Edelény, Hungary
Investigational Site Number : 3480001
🇭🇺Szeged, Hungary
Investigational Site Number : 3800001
🇮🇹Rozzano, Lombardia, Italy
Investigational Site Number : 4840003
🇲🇽Guadalajara, Jalisco, Mexico
Investigational Site Number : 4840004
🇲🇽Durango, Mexico
Investigational Site Number : 6160008
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number : 6160004
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 6420002
🇷🇴Brasov, Romania
Investigational Site Number : 7240005
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 3800004
🇮🇹Firenze, Italy
Investigational Site Number : 3800006
🇮🇹Milano, Italy
Investigational Site Number : 3800005
🇮🇹Varese, Italy
Investigational Site Number : 4840002
🇲🇽Chihuahua, Mexico
Investigational Site Number : 6160001
🇵🇱Krakow, Poland
Investigational Site Number : 6160007
🇵🇱Lodz, Poland
Investigational Site Number : 3800003
🇮🇹Catania, Italy
Investigational Site Number : 6160005
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number : 6160006
🇵🇱Sroda Wielkopolska, Poland
Investigational Site Number : 6200003
🇵🇹Aveiro, Portugal
Investigational Site Number : 6200006
🇵🇹Guimarães, Portugal
Investigational Site Number : 6200007
🇵🇹Santa Maria da Feira, Portugal
Investigational Site Number : 6420003
🇷🇴Cluj-Napoca, Romania
Investigational Site Number : 6420004
🇷🇴Craiova, Romania
Investigational Site Number : 7240001
🇪🇸Sevilla, Andalucia, Spain
Investigational Site Number : 7240008
🇪🇸Hospitalet de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number : 7240004
🇪🇸Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 7240007
🇪🇸Majadahonda, Madrid, Spain
Investigational Site Number : 7240006
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 7520003
🇸🇪Göteborg, Sweden
Investigational Site Number : 7520002
🇸🇪Lund, Sweden
Investigational Site Number : 7520001
🇸🇪Stockholm, Sweden
Investigational Site Number : 8260003
🇬🇧Wigan, Lancashire, United Kingdom
Investigational Site Number : 8260002
🇬🇧Manchester, United Kingdom
Investigational Site Number : 8260001
🇬🇧Newcastle upon Tyne, United Kingdom