EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients

Asthma Clinical Trial

— EVEREST  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04998604
• Other study ID #: LPS16747
• Secondary ID: U1111-1255-47132
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 27, 2021
• Est. completion date: January 2, 2025

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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 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 effect of dupilumab on asthma control at Week 24 compared to omalizumab

• To evaluate the safety of dupilumab and omalizumab

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: January 2, 2025
• Est. primary completion date: October 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Chronic Rhinosinusitis With Nasal Polyps
• Nasal Polyps
• Polyps
• Rhinosinusitis

Intervention

Drug:
• Dupilumab
solution for injection subcutaneous
• Omalizumab
solution for injection subcutaneous
• Placebo
solution for injection subcutaneous

Locations

Country	Name	City	State
Belgium	Investigational Site Number : 0560001	Gent
Belgium	Investigational Site Number : 0560002	Leuven
Belgium	Investigational Site Number : 0560003	Sint-Lambrechts-Woluwe
Canada	Investigational Site Number : 1240004	London	Ontario
Canada	Investigational Site Number : 1240002	Montreal	Quebec
Canada	Investigational Site Number : 1240006	Ottawa	Ontario
Canada	Investigational Site Number : 1240003	Quebec
Czechia	Investigational Site Number : 2030007	Benesov
Czechia	Investigational Site Number : 2030001	Hradec Kralove
Czechia	Investigational Site Number : 2030003	Ostrava - Poruba
Czechia	Investigational Site Number : 2030002	Pardubice
Czechia	Investigational Site Number : 2030012	Plzen
Czechia	Investigational Site Number : 2030010	Praha 10
Czechia	Investigational Site Number : 2030006	Praha 2
Czechia	Investigational Site Number : 2030008	Praha 4
Czechia	Investigational Site Number : 2030004	Praha 5 - Motol
Denmark	Investigational Site Number : 2080003	Aarhus
Denmark	Investigational Site Number : 2080001	Copenhagen
Denmark	Investigational Site Number : 2080004	Herning
Finland	Investigational Site Number : 2460003	Helsinki
Finland	Investigational Site Number : 2460002	Tampere
France	Investigational Site Number : 2500009	Creteil
France	Investigational Site Number : 2500008	Kremlin Bicetre
France	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
Germany	Investigational Site Number : 2760002	Berlin
Germany	Investigational Site Number : 2760004	Düsseldorf
Germany	Investigational Site Number : 2760006	Hamburg
Germany	Investigational Site Number : 2760003	München
Germany	Investigational Site Number : 2760001	Münster
Hungary	Investigational Site Number : 3480004	Budapest
Hungary	Investigational Site Number : 3480007	Budapest
Hungary	Investigational Site Number : 3480005	Debrecen
Hungary	Investigational Site Number : 3480006	Edelény
Hungary	Investigational Site Number : 3480002	Pécs
Hungary	Investigational Site Number : 3480001	Szeged
Italy	Investigational Site Number : 3800003	Catania
Italy	Investigational Site Number : 3800004	Firenze
Italy	Investigational Site Number : 3800006	Milano
Italy	Investigational Site Number : 3800002	Roma	Lazio
Italy	Investigational Site Number : 3800001	Rozzano	Lombardia
Italy	Investigational Site Number : 3800005	Varese
Mexico	Investigational Site Number : 4840002	Chihuahua
Mexico	Investigational Site Number : 4840004	Durango
Mexico	Investigational Site Number : 4840003	Guadalajara	Jalisco
Poland	Investigational Site Number : 6160005	Katowice	Slaskie
Poland	Investigational Site Number : 6160001	Krakow
Poland	Investigational Site Number : 6160007	Lodz
Poland	Investigational Site Number : 6160004	Poznan	Wielkopolskie
Poland	Investigational Site Number : 6160006	Sroda Wielkopolska
Poland	Investigational Site Number : 6160008	Warszawa	Mazowieckie
Portugal	Investigational Site Number : 6200005	Almada
Portugal	Investigational Site Number : 6200003	Aveiro
Portugal	Investigational Site Number : 6200006	Guimarães
Portugal	Investigational Site Number : 6200001	Matosinhos
Portugal	Investigational Site Number : 6200007	Santa Maria da Feira
Romania	Investigational Site Number : 6420002	Brasov
Romania	Investigational Site Number : 6420003	Cluj-Napoca
Romania	Investigational Site Number : 6420004	Craiova
Spain	Investigational Site Number : 7240005	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240008	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Jerez de la Frontera	Cádiz
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 : 7240001	Sevilla	Andalucia
Sweden	Investigational Site Number : 7520003	Göteborg
Sweden	Investigational Site Number : 7520002	Lund
Sweden	Investigational Site Number : 7520001	Stockholm
United Kingdom	Investigational Site Number : 8260002	Manchester
United Kingdom	Investigational Site Number : 8260001	Newcastle upon Tyne
United Kingdom	Investigational Site Number : 8260003	Wigan	Lancashire
United States	Northwestern University Site Number : 8400001	Chicago	Illinois
United States	Rush University Medical Center Site Number : 8400035	Chicago	Illinois
United States	Dept of Otolaryngology, Head and Neck Surgery Site Number : 8400028	Cincinnati	Ohio
United States	Cleveland Clinic Foundation Site Number : 8400029	Cleveland	Ohio
United States	University of Missouri Health Care - University Hospital Site Number : 8400016	Columbia	Missouri
United States	Optimed Research, LTD Site Number : 8400014	Columbus	Ohio
United States	Northwell Health Site Number : 8400044	Great Neck	New York
United States	The University Of Texas Health Science Center At Houston 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	Advanced ENT and Allergy Site Number : 8400013	Louisville	Kentucky
United States	Eastern Virginia Medical School Site Number : 8400010	Norfolk	Virginia
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	University of Rochester Site Number : 8400015	Rochester	New York
United States	Chryaslis Clinical Research Site Number : 8400017	Saint George	Utah
United States	Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027	Tampa	Florida
United States	Essential Medical Research, LLC Site Number : 8400024	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Mexico,  Poland,  Portugal,  Romania,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline to Week 24
Primary	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.	Baseline to Week 24
Secondary	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').	Baseline to Week 24
Secondary	Change from baseline to Week 24 in the nasal congestion (NC) score of the CRSwNP Nasal Symptom Diary	NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').	Baseline to week 24
Secondary	Change from baseline to Week 24 in pre--bronchodilator forced expiratory volume in 1 second (FEV1)	Pre-bronchodilator forced expiratory volume in 1 second (volume of air in liters).	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in 22-Item Sino-nasal Outcome Test (SNOT-22) and	SNOT-22 is a patient-reported outcome (PRO) questionnaire. Score ranges from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)	Nasal Peak Inspiratory flow (nasal flow in liter per minute).	Baseline to Week 24
Secondary	Change from baseline to Week 24 in rhinosinusitis visual analogue scale (VAS)	Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).	Baseline to Week 36
Secondary	Incidence of adverse events of special interest (AESIs)	Incidence of adverse events of special interest (AESIs).	Baseline to Week 36

External Links

•   LPS16747 Chronic Rhinosinusitis with Nasal Polyps Dupilumab Trial website