EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients

NCT04998604 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: LPS16747U1111-1255-47132021-000829-27
• Study Type: interventional
• Target: 360
• Locations: 17 countries
• Sites: 87

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

Conditions

Chronic Rhinosinusitis With Nasal Polyps; Asthma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  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

  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

  Baseline (Day 1) and Week 24

• Change From Baseline to Week 24 in Sino-Nasal Outcome Test 22-Items: Nasal Domain Score

  Baseline (Day 1) and Week 24

Study Arms (2)

Dupilumab 300 mg Q2W

EXPERIMENTAL

Participants received dupilumab 300 milligrams (mg) subcutaneous (SC) injection every 2 weeks (Q2W) for 24 weeks.

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.

Drug: Omalizumab; Drug: Placebo

Interventions

Dupilumab DRUG

solution for injection subcutaneous

Also known as: SAR231893 Dupixent

Dupilumab 300 mg Q2W

Omalizumab DRUG

solution for injection subcutaneous

Also known as: Xolair

Omalizumab 75 to 600 mg Q2W/Q4W

Placebo DRUG

solution for injection subcutaneous

Dupilumab 300 mg Q2W; Omalizumab 75 to 600 mg Q2W/Q4W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (87)

Cedars Sinai Medical Center Site Number : 8400026

Los Angeles, California, 90048, United States

Location

Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027

Tampa, Florida, 33613, United States

Location

Northwestern University Site Number : 8400001

Chicago, Illinois, 60611, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

Advanced ENT and Allergy Site Number : 8400013

Louisville, Kentucky, 40220, United States

Location

University of Missouri Health Care - University Hospital Site Number : 8400016

Columbia, Missouri, 65212, United States

Location

Northwell Health Site Number : 8400044

Great Neck, New York, 11021, United States

Location

University of Rochester Site Number : 8400015

Rochester, New York, 14642, United States

Location

Cleveland Clinic Foundation Site Number : 8400029

Cleveland, Ohio, 44195, United States

Location

Optimed Research, LTD Site Number : 8400014

Columbus, Ohio, 43235, United States

Location

Allergy, Asthma and Clinical Research Center Site Number : 8400037

Oklahoma City, Oklahoma, 73120, United States

Location

Essential Medical Research, LLC Site Number : 8400024

Tulsa, Oklahoma, 74137, United States

Location

Oregon Health & Science University Site Number : 8400031

Portland, Oregon, 97239, United States

Location

University of Texas Health Science Center- Site Number : 8400019

Houston, Texas, 77030, United States

Location

Chryaslis Clinical Research Site Number : 8400017

St. George, Utah, 84790, United States

Location

Eastern Virginia Medical School Site Number : 8400010

Norfolk, Virginia, 23507, United States

Location

Investigational Site Number : 0560001

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560002

Leuven, 3000, Belgium

Location

Investigational Site Number : 0560003

Woluwe-Saint-Lambert, 1200, Belgium

Location

Investigational Site Number : 1240004

London, Ontario, N6A 5A5, Canada

Location

Investigational Site Number : 1240002

Montreal, Quebec, H4A 3J1, Canada

Location

Investigational Site Number : 1240003

Québec, G1V 4G5, Canada

Location

Investigational Site Number : 2030007

Benešov, 256 01, Czechia

Location

Investigational Site Number : 2030001

Hradec Králové, 50005, Czechia

Location

Investigational Site Number : 2030003

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030002

Pardubice, 53203, Czechia

Location

Investigational Site Number : 2030012

Pilsen, 30599, Czechia

Location

Investigational Site Number : 2030010

Prague, 10034, Czechia

Location

Investigational Site Number : 2030006

Prague, 12808, Czechia

Location

Investigational Site Number : 2030008

Prague, 14059, Czechia

Location

Investigational Site Number : 2030004

Praha 5 - Motole, 15006, Czechia

Location

Investigational Site Number : 2080003

Aarhus, 8200, Denmark

Location

Investigational Site Number : 2080001

Copenhagen, 2100, Denmark

Location

Investigational Site Number : 2460003

Helsinki, 00029 HUS, Finland

Location

Investigational Site Number : 2460002

Tampere, 33520, Finland

Location

Investigational Site Number : 2500009

Créteil, 94010, France

Location

Investigational Site Number : 2500006

La Roche-sur-Yon, 85925, France

Location

Investigational Site Number : 2500008

Le Kremlin-Bicêtre, 94275, France

Location

Investigational Site Number : 2500002

Lille, 59037, France

Location

Investigational Site Number : 2500004

Marseille, 13005, France

Location

Investigational Site Number : 2500005

Montpellier, 34295, France

Location

Investigational Site Number : 2500007

Toulouse, 31059, France

Location

Investigational Site Number : 2760002

Berlin, 13353, Germany

Location

Investigational Site Number : 2760004

Düsseldorf, 40225, Germany

Location

Investigational Site Number : 2760003

München, 81377, Germany

Location

Investigational Site Number : 2760001

Münster, 48149, Germany

Location

Investigational Site Number : 3480007

Budapest, 1083, Hungary

Location

Investigational Site Number : 3480004

Budapest, 1115, Hungary

Location

Investigational Site Number : 3480005

Debrecen, 4026, Hungary

Location

Investigational Site Number : 3480006

Edelény, 3780, Hungary

Location

Investigational Site Number : 3480002

Pécs, 7621, Hungary

Location

Investigational Site Number : 3480001

Szeged, 6725, Hungary

Location

Investigational Site Number : 3800002

Rome, Lazio, 00168, Italy

Location

Investigational Site Number : 3800001

Rozzano, Lombardy, 20089, Italy

Location

Investigational Site Number : 3800003

Catania, 95123, Italy

Location

Investigational Site Number : 3800004

Florence, 50134, Italy

Location

Investigational Site Number : 3800006

Milan, 20132, Italy

Location

Investigational Site Number : 3800005

Varese, 21100, Italy

Location

Investigational Site Number : 4840003

Guadalajara, Jalisco, 44100, Mexico

Location

Investigational Site Number : 4840002

Chihuahua City, 31000, Mexico

Location

Investigational Site Number : 4840004

Durango, 34000, Mexico

Location

Investigational Site Number : 6160004

Poznan, Greater Poland Voivodeship, 60-693, Poland

Location

Investigational Site Number : 6160008

Warsaw, Masovian Voivodeship, 04-141, Poland

Location

Investigational Site Number : 6160005

Katowice, Silesian Voivodeship, 40-611, Poland

Location

Investigational Site Number : 6160001

Krakow, 30-033, Poland

Location

Investigational Site Number : 6160007

Lodz, 90141, Poland

Location

Investigational Site Number : 6160006

Środa Wielkopolska, 63000, Poland

Location

Investigational Site Number : 6200005

Almada, 2801-951, Portugal

Location

Investigational Site Number : 6200003

Aveiro, 3814-501, Portugal

Location

Investigational Site Number : 6200006

Guimarães, 4810-061, Portugal

Location

Investigational Site Number : 6200001

Matosinhos Municipality, 4454-509, Portugal

Location

Investigational Site Number : 6200007

Santa Maria da Feira, 4520-211, Portugal

Location

Investigational Site Number : 6420002

Brasov, 500283, Romania

Location

Investigational Site Number : 6420004

Craiova, 200222, Romania

Location

Investigational Site Number : 7240001

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number : 7240005

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240008

L'Hospitalet de Llobregat, Barcelona [Barcelona], 08907, Spain

Location

Investigational Site Number : 7240003

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Investigational Site Number : 7240007

Majadahonda, Madrid, 28222, Spain

Location

Investigational Site Number : 7240004

Madrid / Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 7240006

Pamplona, Navarre, 31080, Spain

Location

Investigational Site Number : 7520003

Gothenburg, 413 45, Sweden

Location

Investigational Site Number : 7520002

Lund, 221 85, Sweden

Location

Investigational Site Number : 7520001

Stockholm, 171 76, Sweden

Location

Investigational Site Number : 8260003

Wigan, Lancashire, WN6 9EP, United Kingdom

Location

Investigational Site Number : 8260002

Manchester, M23 9LT, United Kingdom

Location

Investigational Site Number : 8260001

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• De 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.

  PMID: 41033334 DERIVED

• 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.

  PMID: 35837739 DERIVED

Related Links

• LPS16747 Chronic Rhinosinusitis with Nasal Polyps Dupilumab Trial website
• LPS16747 Plain Language Results Summary

MeSH Terms

Conditions

Asthma

Interventions

dupilumab; Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo injections will be administered as needed to blind the number of active dupilumab and omalizumab injections
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 10, 2021
• Study Start: September 27, 2021
• Primary Completion: October 16, 2024
• Study Completion: December 27, 2024
• Last Updated: October 23, 2025
• Results First Posted: October 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

FR (7); CA (3); BE (3); HU (6); RO (2); PL (6); PT (5); ME (3); DE (4); US (16); CZ (9); GB (3); SE (3); IT (6); FI (2); DK (2); ES (7)