Chronic Rhinosinusitis With Nasal PolypsPhase 4EVERESTNCT04998604
EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients
A Phase 4 study testing Dupilumab and Omalizumab in people with Chronic Rhinosinusitis With Nasal Polyps and Asthma, run by Sanofi at 87 sites in 17 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Rhinosinusitis With Nasal Polyps, Asthma
- What is being tested?
- Dupilumab and Omalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 360 participants
- Where
- 87 sitesin 17 countries
- Study dates
- 27 Sep 2021to 27 Dec 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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 was to 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.
Who cannot join
- Participants were excluded from the study if any of the following criteria apply:
- Participants who underwent any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1.
- Participants who 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
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- 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 participant's potential participation in a clinical trial.
Trial locations and contacts
87 sites in 17 countries.
87 sites in 17 countries
United States16 sites
Northwestern University Site Number : 8400001
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
Cleveland Clinic Foundation Site Number : 8400029
Cleveland, Ohio, 44195
University of Missouri Health Care - University Hospital Site Number : 8400016
Columbia, Missouri, 65212
Optimed Research, LTD Site Number : 8400014
Columbus, Ohio, 43235
Northwell Health Site Number : 8400044
Great Neck, New York, 11021
University of Texas Health Science Center- Site Number : 8400019
Houston, Texas, 77030
Cedars Sinai Medical Center Site Number : 8400026
Los Angeles, California, 90048
Advanced ENT and Allergy Site Number : 8400013
Louisville, Kentucky, 40220
Eastern Virginia Medical School Site Number : 8400010
Norfolk, Virginia, 23507
Allergy, Asthma and Clinical Research Center Site Number : 8400037
Oklahoma City, Oklahoma, 73120
Oregon Health & Science University Site Number : 8400031
Portland, Oregon, 97239
University of Rochester Site Number : 8400015
Rochester, New York, 14642
Chryaslis Clinical Research Site Number : 8400017
St. George, Utah, 84790
Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027
Tampa, Florida, 33613
Essential Medical Research, LLC Site Number : 8400024
Tulsa, Oklahoma, 74137
Czechia9 sites
Investigational Site Number : 2030007
Benešov, 256 01
Investigational Site Number : 2030001
Hradec Králové, 50005
Investigational Site Number : 2030003
Ostrava - Poruba, 70852
Investigational Site Number : 2030002
Pardubice, 53203
Investigational Site Number : 2030012
Pilsen, 30599
Investigational Site Number : 2030010
Prague, 10034
Investigational Site Number : 2030006
Prague, 12808
Investigational Site Number : 2030008
Prague, 14059
Investigational Site Number : 2030004
Praha 5 - Motole, 15006
France7 sites
Investigational Site Number : 2500009
Créteil, 94010
Investigational Site Number : 2500006
La Roche-sur-Yon, 85925
Investigational Site Number : 2500008
Le Kremlin-Bicêtre, 94275
Investigational Site Number : 2500002
Lille, 59037
Investigational Site Number : 2500004
Marseille, 13005
Investigational Site Number : 2500005
Montpellier, 34295
Investigational Site Number : 2500007
Toulouse, 31059
Spain7 sites
Investigational Site Number : 7240005
Barcelona, Barcelona [Barcelona], 08036
Investigational Site Number : 7240003
Jerez de la Frontera, Cádiz, 11407
Investigational Site Number : 7240008
L'Hospitalet de Llobregat, Barcelona [Barcelona], 08907
Investigational Site Number : 7240004
Madrid / Madrid, Madrid, Comunidad de, 28040
Investigational Site Number : 7240007
Majadahonda, Madrid, 28222
Investigational Site Number : 7240006
Pamplona, Navarre, 31080
Investigational Site Number : 7240001
Seville, Andalusia, 41009
Hungary6 sites
Investigational Site Number : 3480007
Budapest, 1083
Investigational Site Number : 3480004
Budapest, 1115
Investigational Site Number : 3480005
Debrecen, 4026
Investigational Site Number : 3480006
Edelény, 3780
Investigational Site Number : 3480002
Pécs, 7621
Investigational Site Number : 3480001
Szeged, 6725
Italy6 sites
Investigational Site Number : 3800003
Catania, 95123
Investigational Site Number : 3800004
Florence, 50134
Investigational Site Number : 3800006
Milan, 20132
Investigational Site Number : 3800002
Rome, Lazio, 00168
Investigational Site Number : 3800001
Rozzano, Lombardy, 20089
Investigational Site Number : 3800005
Varese, 21100
Poland6 sites
Investigational Site Number : 6160005
Katowice, Silesian Voivodeship, 40-611
Investigational Site Number : 6160001
Krakow, 30-033
Investigational Site Number : 6160007
Lodz, 90141
Investigational Site Number : 6160004
Poznan, Greater Poland Voivodeship, 60-693
Investigational Site Number : 6160006
Środa Wielkopolska, 63000
Investigational Site Number : 6160008
Warsaw, Masovian Voivodeship, 04-141
Portugal5 sites
Investigational Site Number : 6200005
Almada, 2801-951
Investigational Site Number : 6200003
Aveiro, 3814-501
Investigational Site Number : 6200006
Guimarães, 4810-061
Investigational Site Number : 6200001
Matosinhos Municipality, 4454-509
Investigational Site Number : 6200007
Santa Maria da Feira, 4520-211
Germany4 sites
Investigational Site Number : 2760002
Berlin, 13353
Investigational Site Number : 2760004
Düsseldorf, 40225
Investigational Site Number : 2760003
München, 81377
Investigational Site Number : 2760001
Münster, 48149
Belgium3 sites
Investigational Site Number : 0560001
Ghent, 9000
Investigational Site Number : 0560002
Leuven, 3000
Investigational Site Number : 0560003
Woluwe-Saint-Lambert, 1200
Canada3 sites
Investigational Site Number : 1240004
London, Ontario, N6A 5A5
Investigational Site Number : 1240002
Montreal, Quebec, H4A 3J1
Investigational Site Number : 1240003
Québec, G1V 4G5
Mexico3 sites
Investigational Site Number : 4840002
Chihuahua City, 31000
Investigational Site Number : 4840004
Durango, 34000
Investigational Site Number : 4840003
Guadalajara, Jalisco, 44100
Sweden3 sites
Investigational Site Number : 7520003
Gothenburg, 413 45
Investigational Site Number : 7520002
Lund, 221 85
Investigational Site Number : 7520001
Stockholm, 171 76
United Kingdom3 sites
Investigational Site Number : 8260002
Manchester, M23 9LT
Investigational Site Number : 8260001
Newcastle upon Tyne, NE7 7DN
Investigational Site Number : 8260003
Wigan, Lancashire, WN6 9EP
Denmark2 sites
Investigational Site Number : 2080003
Aarhus, 8200
Investigational Site Number : 2080001
Copenhagen, 2100
Finland2 sites
Investigational Site Number : 2460003
Helsinki, 00029 HUS
Investigational Site Number : 2460002
Tampere, 33520
Romania2 sites
Investigational Site Number : 6420002
Brasov, 500283
Investigational Site Number : 6420004
Craiova, 200222
About this study
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
Primary Objective
-To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell
Read more
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
Read the 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.
- Conditions
- Chronic Rhinosinusitis With Nasal Polyps, Asthma
- Being tested
- Dupilumab, Omalizumab, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DupilumabDrug
Also called SAR231893 Dupixent
solution for injection subcutaneous
OmalizumabDrug
Also called Xolair
solution for injection subcutaneous
PlaceboDrug
solution for injection subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Dupilumab 300 mg Q2W | Experimental | Participants received dupilumab 300 milligrams (mg) subcutaneous (SC) injection every 2 weeks (Q2W) for 24 weeks. Receives: Drug: Dupilumab; Drug: Placebo |
| Omalizumab 75 to 600 mg Q2W/Q4W | Experimental | Participants received omalizumab 75 to 600 mg SC injection Q2W/every 4 weeks (Q4W) based on their serum immunoglobulin E (IgE) levels and body weight for 24 weeks. Receives: Drug: Omalizumab; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 24 in Nasal Polyp Score
The NPS was assessed by the independent physician to grade the extent/severity of nasal polyps based on evaluation by nasal endoscopy. The NPS scores for each nostril was graded based on polyp size from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior nasal cavity). The total NPS score was calculated as the sum of right and left nostril scores and ranged from 0 (no polyps) to 8 (large polyps). Higher scores indicated more extensive or severe nasal polyps. Negative change from baseline indicated less severity of nasal polyps. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Measured: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test
The UPSIT was a 40-item test to quantitatively assess human olfactory function. The UPSIT test consisted of 4 booklets, each containing 10 odorants with 1 odorant per page. The participant was asked to release the odorant by rubbing the brown-strip (contained odorant microcapsules) with the tip of a pencil and to indicate which of 4 words best described the odor. Thus, each participant received a score out of 40 possible correct answers. The total UPSIT score ranged from 0 (loss of smell/anosmia) to 40 (normal sense of smell/normosmia). Higher scores indicated better olfactory function. Positive change from baseline indicated normal olfactory function. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Measured: Baseline (Day 1) and Week 24
Secondary outcomes (8)
Change From Baseline to Week 24 in the Loss of Smell Score of the Chronic Rhinosinusitis With Nasal Polyp (CRSwNP) Nasal Symptom Diary
The nasal symptom diary was designed to assess the severity of chronic rhinosinusitis nasal symptoms daily. These symptoms included nasal congestion (NC)/obstruction, loss of smell, anterior rhinorrhea, and posterior rhinorrhea. The severity of loss of smell was scored by participants using a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, caused interference with activities, or daily living). Higher scores indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline value was calculated by averaging the data collected/recorded from Day -6 to Day 1.
Measured: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in the Nasal Congestion Score of the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary
The nasal symptom diary was designed to assess the severity of chronic rhinosinusitis nasal symptoms daily. These symptoms included NC/obstruction, loss of smell, anterior rhinorrhea, and posterior rhinorrhea. The severity of NC was scored by participants using a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, caused interference with activities, or daily living). Higher scores indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline value was calculated by averaging the data collected/recorded from Day -6 to Day 1.
Measured: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Total Symptom Score (TSS) Derived From the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary
The TSS is a composite score consisted of the following symptoms assessed daily in the morning: NC/obstruction, decreased/loss of sense of smell, and rhinorrhea (average of anterior/posterior nasal discharge). Each item was scored on a scale ranged from 0 to 3 (where, 0= no symptoms, 1= mild symptoms, 2= moderate symptoms and 3= severe symptoms that were hard to tolerate, and caused interference with activities, or daily living). Higher score indicated greater symptom severity. The TSS score was calculated by summing the individual symptom score and ranged from 0 (no symptoms) to 9 (severe symptoms). Higher scores on the TSS indicated greater symptom severity. Negative change from baseline indicated less severe symptom. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.
Measured: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items (SNOT-22) Total Score
The SNOT-22 is a patient-reported outcome questionnaire designed to assess the impact of chronic rhinosinusitis on participants' health-related quality of life. The SNOT-22 consisted of 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of chronic rhinosinusitis. Each item was rated on a 6-point Likert scale response option, score ranged from 0 (no problem) to 5 (problem as bad as it can be). The SNOT-22 total score was the sum of each item score, and it ranged from 0 (no problem) to 110 (problem as bad as it can be). Higher scores indicated greater rhinosinusitis-related health burden, meaning for this parameter lower score indicated better condition. Negative change from baseline indicated improvement in health-related quality of life. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Measured: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items: Nasal Domain Score
SNOT-22 is a patient-reported outcome questionnaire designed to assess impact of chronic rhinosinusitis on participants' health-related quality of life. SNOT-22 was categorized into 5 domains: Nasal (items 1, 2, 3, 4, 5, 6, 7 and 12); Ear/Facial (items 8, 9, 10 and 11); Sleep (items 13, 14, 15 and 16); Function (items 17, 18 and 19); Emotion (items 20, 21 and 22). Each item of Nasal domain was rated on a 6-point Likert scale ranged from 0 (no problem) to 5 (problem as bad as it can be) with higher score indicated greater rhinosinusitis-related health burden. Total score of Nasal domain was average score of items of nasal domain, and ranged from 0 (no problem) to 5 (problem as bad as it can be), where higher score indicated greater rhinosinusitis-related health burden. Negative change from baseline indicated improvement in health-related quality of life. Baseline was defined as last available valid (non-missing) value up to and including day of first administration of study treatment.
Measured: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)
The NPIF evaluation represented a physiologic measure of the air flow through both nasal cavities during forced inspiration. The NPIF is the best validated technique for the evaluation of nasal flow through the nose. Participants were issued an NPIF meter and were instructed on the use of the device and written instructions on the use of the NPIF meter was provided. Higher NPIF values were indicative of better nasal air flow. Positive change from baseline indicated better nasal air flow. Baseline was the mean measurement recorded for the 7 days (Day -6 to Day 1) prior to first dose of study treatment.
Measured: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Rhinosinusitis Visual Analogue Scale (Rhinosinusitis VAS)
The rhinosinusitis severity VAS was used to evaluate the overall severity of the rhinosinusitis. It is a recommended scale to determine the participant's disease severity and to guide the treatment for chronic rhinosinusitis. The participants were asked to answer the following question: "How troublesome are your symptoms of your rhinosinusitis" on a 10-centimeter VAS from 0 (not troublesome) to 10 (worst thinkable troublesome). Higher scores on the VAS score indicated more severe chronic rhinosinusitis. Negative change from baseline indicated less severity of rhinosinusitis. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Measured: Baseline (Day 1) and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. The TEAEs was defined as an AEs that occurred from the first administration of the study treatment (on Day 1) up to 98 days after the last dose of study treatment administration.
Measured: From first dose of study treatment administration (Day 1) up to 98 days after the last dose of study treatment administration (considering the maximum duration of treatment exposure) i.e., up to approximately 329 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start27 Sep 2021
- Primary completion16 Oct 2024
- Study completion27 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Rhinosinusitis With Nasal PolypsStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04998604
- Sponsor's protocol ID
- LPS16747
- Other IDs
- U1111-1255-4713, 2021-000829-27
- Acronym
- EVEREST
- Status last verified
- Sep 2025
- First submitted
- 9 Aug 2021
- Last updated
- 23 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
De Corso E, Jaffee H, Bertels X, Gascon Moreno V, Silva M. Dupilumab versus omalizumab in chronic rhinosinusitis with nasal polyps and asthma: a plain language summary. Expert Opin Biol Ther. 2026 Aug 26:1-16. doi: 10.1080/14712598.2026.2719891. Online ahead of print.
PubMed 42644458De Corso E, Canonica GW, Heffler E, Springer M, Grzegorzek T, Viana M, Horvath Z, Mullol J, Gevaert P, Michel J, Peters AT, Wagenmann M, Zaghloul S, Zhang M, Corbett M, Nash S, Angello JT, Radwan A, Deniz Y, Martin A, Hellings PW. Dupilumab versus omalizumab in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma (EVEREST): a multicentre, randomised, double-blind, head-to-head phase 4 trial. Lancet Respir Med. 2025 Dec;13(12):1067-1077. doi: 10.1016/S2213-2600(25)00287-5. Epub 2025 Sep 28.
PubMed 41033334De 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.
PubMed 35837739
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04998604
- Acronym / sponsor ID
- EVEREST / LPS16747
- Conditions
- Chronic Rhinosinusitis With Nasal Polyps, Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 27 Sep 2021 (actual)
- Primary completion
- 16 Oct 2024 (actual)
- Study completion
- 27 Dec 2024 (actual)
- First posted
- 10 Aug 2021 (actual)
- Results
- Posted 23 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dupilumab 300 mg Q2W | Experimental | Drug: Dupilumab, Drug: PlaceboParticipants received dupilumab 300 milligrams (mg) subcutaneous (SC) injection every 2 weeks (Q2W) for 24 weeks. |
| Omalizumab 75 to 600 mg Q2W/Q4W | Experimental | Drug: Omalizumab, Drug: PlaceboParticipants received omalizumab 75 to 600 mg SC injection Q2W/every 4 weeks (Q4W) based on their serum immunoglobulin E (IgE) levels and body weight for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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 was to 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).
Key exclusion criteria (13 listed)
- Participants who underwent any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1.
- Participants who 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DupilumabAlso: SAR231893 Dupixentsolution for injection subcutaneous | Drug | Dupilumab 300 mg Q2W |
| OmalizumabAlso: Xolairsolution for injection subcutaneous | Drug | Omalizumab 75 to 600 mg Q2W/Q4W |
| Placebosolution for injection subcutaneous | Drug | Dupilumab 300 mg Q2W, Omalizumab 75 to 600 mg Q2W/Q4W |
Primary outcome
Change From Baseline to Week 24 in Nasal Polyp Score
Time frame: Baseline (Day 1) and Week 24
The NPS was assessed by the independent physician to grade the extent/severity of nasal polyps based on evaluation by nasal endoscopy. The NPS scores for each nostril was graded based on polyp size from 0 (no polyps) to 4 (large polyps causing complete obstruction of the inferior nasal cavity). The total NPS score was calculated as the sum of right and left nostril scores and ranged from 0 (no polyps) to 8 (large polyps). Higher scores indicated more extensive or severe nasal polyps. Negative change from baseline indicated less severity of nasal polyps. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
Change From Baseline to Week 24 in University of Pennsylvania Smell Identification Test
Time frame: Baseline (Day 1) and Week 24
The UPSIT was a 40-item test to quantitatively assess human olfactory function. The UPSIT test consisted of 4 booklets, each containing 10 odorants with 1 odorant per page. The participant was asked to release the odorant by rubbing the brown-strip (contained odorant microcapsules) with the tip of a pencil and to indicate which of 4 words best described the odor. Thus, each participant received a score out of 40 possible correct answers. The total UPSIT score ranged from 0 (loss of smell/anosmia) to 40 (normal sense of smell/normosmia). Higher scores indicated better olfactory function. Positive change from baseline indicated normal olfactory function. Baseline was defined as the last available valid (non-missing) value up to and including the day of first administration of study treatment.
8 secondary outcomes
Change From Baseline to Week 24 in the Loss of Smell Score of the Chronic Rhinosinusitis With Nasal Polyp (CRSwNP) Nasal Symptom Diary
Time frame: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in the Nasal Congestion Score of the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary
Time frame: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Total Symptom Score (TSS) Derived From the Chronic Rhinosinusitis With Nasal Polyp Nasal Symptom Diary
Time frame: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items (SNOT-22) Total Score
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items: Nasal Domain Score
Time frame: Baseline (Day 1) and Week 24
Change From Baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)
Time frame: Baseline (average of Day -6 to Day 1) and Week 24
Change From Baseline to Week 24 in Rhinosinusitis Visual Analogue Scale (Rhinosinusitis VAS)
Time frame: Baseline (Day 1) and Week 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs)
Time frame: From first dose of study treatment administration (Day 1) up to 98 days after the last dose of study treatment administration (considering the maximum duration of treatment exposure) i.e., up to approximately 329 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42644458De Corso E, Jaffee H, Bertels X, Gascon Moreno V, Silva M. Dupilumab versus omalizumab in chronic rhinosinusitis with nasal polyps and asthma: a plain language summary. Expert Opin Biol Ther. 2026 Aug 26:1-16. doi: 10.1080/14712598.2026.2719891. Online ahead of print.
- Derived from this study: PubMed 41033334De Corso E, Canonica GW, Heffler E, Springer M, Grzegorzek T, Viana M, Horvath Z, Mullol J, Gevaert P, Michel J, Peters AT, Wagenmann M, Zaghloul S, Zhang M, Corbett M, Nash S, Angello JT, Radwan A, Deniz Y, Martin A, Hellings PW. Dupilumab versus omalizumab in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma (EVEREST): a multicentre, randomised, double-blind, head-to-head phase 4 trial. Lancet Respir Med. 2025 Dec;13(12):1067-1077. doi: 10.1016/S2213-2600(25)00287-5. Epub 2025 Sep 28.
- Derived from this study: PubMed 35837739De 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.
- LPS16747 Chronic Rhinosinusitis with Nasal Polyps Dupilumab Trial websiteLink provided by the sponsor.
- LPS16747 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
87 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dupilumab and Omalizumab in people with Chronic Rhinosinusitis With Nasal Polyps and Asthma, run by Sanofi at 87 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 87 sites in United States, Czechia, France, Spain, Hungary and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 24 in Nasal Polyp Score (time frame: Baseline (Day 1) and Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04998604, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2025.