Clinical trial NCT04998604: EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients
Official title: A Randomized, Double-blind, Head-to-head Comparison of Dupilumab Versus Omalizumab in Severe Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) and Comorbid Asthma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2021-08-10
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Exclusion Criteria:

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.

Primary outcomes:
measure: Change from baseline to Week 24 in Nasal Polyp Score (NPS)
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom Diary
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in the nasal congestion (NC) score of the CRSwNP Nasal Symptom Diary
timeFrame: Baseline to week 24
measure: Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom Diary
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in 22-Item Sino-nasal Outcome Test (SNOT-22) and
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in SNOT-22 nasal domain score
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)
timeFrame: Baseline to Week 24
measure: Change from baseline to Week 24 in rhinosinusitis visual analogue scale (VAS)
timeFrame: Baseline to Week 24
measure: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Baseline to Week 36
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Baseline to Week 36
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Modena Allergy + Asthma Site Number : 8400033
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Site Number : 8400026
state: California
city: Tampa
country: United States
facility: Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027
state: Florida
city: Chicago
country: United States
facility: Northwestern University Site Number : 8400001
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Site Number : 8400035
state: Illinois
city: Louisville
country: United States
facility: Advanced ENT and Allergy Site Number : 8400013
state: Kentucky
city: Columbia
country: United States
facility: University of Missouri Health Care - University Hospital Site Number : 8400016
state: Missouri
city: Great Neck
country: United States
facility: Northwell Health Site Number : 8400044
state: New York
city: Rochester
country: United States
facility: University of Rochester Site Number : 8400015
state: New York
city: Cincinnati
country: United States
facility: Dept of Otolaryngology, Head and Neck Surgery Site Number : 8400028
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Site Number : 8400029
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD Site Number : 8400014
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center Site Number : 8400037
state: Oklahoma
city: Tulsa
country: United States
facility: Essential Medical Research, LLC Site Number : 8400024
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University Site Number : 8400031
state: Oregon
city: Houston
country: United States
facility: University of Texas Health Science Center- Site Number : 8400019
state: Texas
city: Saint George
country: United States
facility: Chryaslis Clinical Research Site Number : 8400017
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical School Site Number : 8400010
state: Virginia
city: Gent
country: Belgium
facility: Investigational Site Number : 0560001
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560002
city: Sint-Lambrechts-Woluwe
country: Belgium
facility: Investigational Site Number : 0560003
city: London
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Ottawa
country: Canada
facility: Investigational Site Number : 1240006
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240003
city: Benesov
country: Czechia
facility: Investigational Site Number : 2030007
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number : 2030001
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 2030003
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030002
city: Plzen
country: Czechia
facility: Investigational Site Number : 2030012
city: Praha 10
country: Czechia
facility: Investigational Site Number : 2030010
city: Praha 2
country: Czechia
facility: Investigational Site Number : 2030006
city: Praha 4
country: Czechia
facility: Investigational Site Number : 2030008
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number : 2030004
city: Aarhus
country: Denmark
facility: Investigational Site Number : 2080003
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460003
city: Tampere
country: Finland
facility: Investigational Site Number : 2460002
city: Creteil
country: France
facility: Investigational Site Number : 2500009
city: Kremlin Bicetre
country: France
facility: Investigational Site Number : 2500008
city: La Roche sur Yon
country: France
facility: Investigational Site Number : 2500006
city: Lille
country: France
facility: Investigational Site Number : 2500002
city: Marseille
country: France
facility: Investigational Site Number : 2500004
city: Montpellier
country: France
facility: Investigational Site Number : 2500005
city: Nantes
country: France
facility: Investigational Site Number : 2500001
city: Toulouse
country: France
facility: Investigational Site Number : 2500007
city: Vandoeuvre-les-nancy
country: France
facility: Investigational Site Number : 2500003
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Düsseldorf
country: Germany
facility: Investigational Site Number : 2760004
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760006
city: München
country: Germany
facility: Investigational Site Number : 2760003
city: Münster
country: Germany
facility: Investigational Site Number : 2760001
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480007
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480004
city: Debrecen
country: Hungary
facility: Investigational Site Number : 3480005
city: Edelény
country: Hungary
facility: Investigational Site Number : 3480006
city: Pécs
country: Hungary
facility: Investigational Site Number : 3480002
city: Szeged
country: Hungary
facility: Investigational Site Number : 3480001
city: Roma
country: Italy
facility: Investigational Site Number : 3800002
state: Lazio
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Catania
country: Italy
facility: Investigational Site Number : 3800003
city: Firenze
country: Italy
facility: Investigational Site Number : 3800004
city: Milano
country: Italy
facility: Investigational Site Number : 3800006
city: Varese
country: Italy
facility: Investigational Site Number : 3800005
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840003
state: Jalisco
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840002
city: Durango
country: Mexico
facility: Investigational Site Number : 4840004
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160008
state: Mazowieckie
city: Katowice
country: Poland
facility: Investigational Site Number : 6160005
state: Slaskie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160004
state: Wielkopolskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160001
city: Lodz
country: Poland
facility: Investigational Site Number : 6160007
city: Sroda Wielkopolska
country: Poland
facility: Investigational Site Number : 6160006
city: Almada
country: Portugal
facility: Investigational Site Number : 6200005
city: Aveiro
country: Portugal
facility: Investigational Site Number : 6200003
city: Guimarães
country: Portugal
facility: Investigational Site Number : 6200006
city: Matosinhos
country: Portugal
facility: Investigational Site Number : 6200001
city: Santa Maria da Feira
country: Portugal
facility: Investigational Site Number : 6200007
city: Brasov
country: Romania
facility: Investigational Site Number : 6420002
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number : 6420003
city: Craiova
country: Romania
facility: Investigational Site Number : 6420004
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240001
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240005
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240008
state: Barcelona [Barcelona]
city: Jerez de la Frontera
country: Spain
facility: Investigational Site Number : 7240003
state: Cádiz
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240007
state: Madrid
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240006
state: Navarra
city: Göteborg
country: Sweden
facility: Investigational Site Number : 7520003
city: Lund
country: Sweden
facility: Investigational Site Number : 7520002
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Wigan
country: United Kingdom
facility: Investigational Site Number : 8260003
state: Lancashire
city: Manchester
country: United Kingdom
facility: Investigational Site Number : 8260002
city: Newcastle upon Tyne
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
References:
citation: De Prado Gomez PharmD MSc L, Khan Mbbs Mph AH, Peters Md AT, Bachert Md PhD C, Wagenmann Md M, Heffler Md PhD E, Hopkins BMBCh C, Hellings Md PhD PW, Zhang PhD M, Xing PhD J, Rowe Md P, Jacob-Nara Md Mph DHSc JA. Efficacy and Safety of Dupilumab Versus Omalizumab in Chronic Rhinosinusitis With Nasal Polyps and Asthma: EVEREST Trial Design. Am J Rhinol Allergy. 2022 Nov;36(6):788-795. doi: 10.1177/19458924221112211. Epub 2022 Jul 15.