EVEREST: EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04998604

Collaborator

Regeneron Pharmaceuticals (Industry)

422

Enrollment

Locations

Arms

28.4

Anticipated Duration (Months)

6.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 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

Condition or Disease	Intervention/Treatment	Phase
Chronic Rhinosinusitis With Nasal Polyps Asthma	Drug: Dupilumab Drug: Omalizumab Drug: Placebo	Phase 4

Detailed Description

Study duration per participant will be 40 weeks. The study will comprise 3 periods: up to 4 weeks screening and run-in period; 24 weeks Randomized investigational medicinal product (IMP) intervention period; up to 12 weeks follow-up period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

422 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Placebo injections will be administered as needed to blind the number of active dupilumab and omalizumab injections

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 27, 2021

Anticipated Primary Completion Date :

Oct 17, 2023

Anticipated Study Completion Date :

Feb 7, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab Dosing every 2 weeks (Q2W)	Drug: Dupilumab solution for injection subcutaneous Other Names: SAR231893 Dupixent Drug: Placebo solution for injection subcutaneous
Experimental: Omalizumab Dosing Q2W or every 4 weeks (Q4W)	Drug: Omalizumab solution for injection subcutaneous Other Names: Xolair Drug: Placebo solution for injection subcutaneous

Arm

Intervention/Treatment

Experimental: Dupilumab

Dosing every 2 weeks (Q2W)

Drug: Dupilumab

solution for injection subcutaneous

Other Names:

SAR231893 Dupixent

Drug: Placebo

solution for injection subcutaneous

Experimental: Omalizumab

Dosing Q2W or every 4 weeks (Q4W)

Drug: Omalizumab

solution for injection subcutaneous

Other Names:

Xolair

Drug: Placebo

solution for injection subcutaneous

Outcome Measures

Primary Outcome Measures

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

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 pre-bronchodilator forced expiratory volume in 1 second (FEV1) [Baseline to Week 24]
Pre-bronchodilator forced expiratory volume in 1 second (volume of air in liters).
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.
Change from baseline to Week 24 in 7-item Asthma Control Questionnaire (ACQ-7) [Baseline to Week 24]
Asthma control with 6 questions plus FEV1 measure. Score ranges from 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 at 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 at time of randomization (Visit 2).
Participants with a physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 for ≥12 months 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.
Pre-bronchodilator FEV1 ≤85% of predicted normal at Visit 1 (screening visit) and Visit 2, prior to randomization.
Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novak Clinical Research-Site Number:8400018	Tucson	Arizona	United States	85710
2	Northwestern University-Site Number:8400001	Chicago	Illinois	United States	60611
3	Advanced ENT and Allergy-Site Number:8400013	Louisville	Kentucky	United States	40220
4	University of Missouri Health Care - University Hospital-Site Number:8400016	Columbia	Missouri	United States	65212
5	University of Rochester-Site Number:8400015	Rochester	New York	United States	14642
6	Dept of Otolaryngology, Head and Neck Surgery-Site Number:8400028	Cincinnati	Ohio	United States	45267
7	Optimed Research, LTD-Site Number:8400014	Columbus	Ohio	United States	43235
8	The University Of Texas Health Science Center At Houston-Site Number:8400019	Houston	Texas	United States	77030
9	Chryaslis Clinical Research-Site Number:8400017	Saint George	Utah	United States	84790
10	Investigational Site Number :0560003	Bruxelles		Belgium	1200
11	Investigational Site Number :0560001	Gent		Belgium	9000
12	Investigational Site Number :0560002	Leuven		Belgium	3000
13	Investigational Site Number :2030007	Benesov		Czechia	256 01
14	Investigational Site Number :2030001	Hradec Kralove		Czechia	50005
15	Investigational Site Number :2030003	Ostrava - Poruba		Czechia	70852
16	Investigational Site Number :2030002	Pardubice		Czechia	53203
17	Investigational Site Number :2030012	Plzen		Czechia	30599
18	Investigational Site Number :2030010	Praha 10		Czechia	10034
19	Investigational Site Number :2030006	Praha 2		Czechia	12808
20	Investigational Site Number :2030008	Praha 4		Czechia	14059
21	Investigational Site Number :2030004	Praha 5 - Motol		Czechia	15006
22	Investigational Site Number :2080001	Copenhagen		Denmark	2100
23	Investigational Site Number :2500009	Creteil		France	94010
24	Investigational Site Number :2500008	Kremlin Bicetre		France	94275
25	Investigational Site Number :2500006	La Roche sur Yon		France	85925
26	Investigational Site Number :2500002	Lille		France	59037
27	Investigational Site Number :2500004	Marseille		France	13005
28	Investigational Site Number :2500005	Montpellier		France	34295
29	Investigational Site Number :2500001	Nantes		France	44093
30	Investigational Site Number :2500007	Toulouse		France	31059
31	Investigational Site Number :2500003	Vandoeuvre-les-nancy		France	54511
32	Investigational Site Number :2760002	Berlin		Germany	13353
33	Investigational Site Number :2760004	Düsseldorf		Germany	40225
34	Investigational Site Number :2760003	München		Germany	81377
35	Investigational Site Number :2760001	Münster		Germany	48149
36	Investigational Site Number :3480007	Budapest		Hungary	1083
37	Investigational Site Number :3480004	Budapest		Hungary	1115
38	Investigational Site Number :3480006	Edelény		Hungary	3780
39	Investigational Site Number :3480002	Pécs		Hungary	7621
40	Investigational Site Number :3480001	Szeged		Hungary	6725
41	Investigational Site Number :3800002	Roma	Lazio	Italy	00168
42	Investigational Site Number :3800001	Rozzano	Milano	Italy	20089
43	Investigational Site Number :3800006	Milano		Italy	20132
44	Investigational Site Number :6160008	Warszawa	Mazowieckie	Poland	04-141
45	Investigational Site Number :6160005	Katowice	Slaskie	Poland	40-611
46	Investigational Site Number :6160004	Poznan	Wielkopolskie	Poland	60-693
47	Investigational Site Number :6160001	Krakow		Poland	30-033
48	Investigational Site Number :6160007	Lodz		Poland	90141
49	Investigational Site Number :6160006	Sroda Wielkopolska		Poland	63000
50	Investigational Site Number :6200005	Almada		Portugal	2801-951
51	Investigational Site Number :6200003	Aveiro		Portugal	3810-501
52	Investigational Site Number :6200006	Guimarães		Portugal	4810-061
53	Investigational Site Number :6200001	Matosinhos		Portugal	4464-513
54	Investigational Site Number :6420002	Brasov		Romania	500283
55	Investigational Site Number :7240001	Sevilla	Andalucia	Spain	41009
56	Investigational Site Number :7240005	Barcelona	Barcelona [Barcelona]	Spain	08036
57	Investigational Site Number :7240002	Santiago de Compostela	Galicia [Galicia]	Spain	15706
58	Investigational Site Number :7240006	Pamplona	Navarra	Spain	31008
59	Investigational Site Number :7240003	Jerez de la Frontera		Spain	11407
60	Investigational Site Number :7240004	Madrid		Spain	28040
61	Investigational Site Number :7520003	Göteborg		Sweden	413 45
62	Investigational Site Number :7520002	Lund		Sweden	221 85
63	Investigational Site Number :7520001	Stockholm		Sweden	171 76
64	Investigational Site Number :8260003	Wigan	Lancashire	United Kingdom	WN6 9EP
65	Investigational Site Number :8260002	Manchester		United Kingdom	M23 9LT
66	Investigational Site Number :8260001	Newcastle upon Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

Sanofi
Regeneron Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT04998604

Other Study ID Numbers:

LPS16747
2021-000829-27
U1111-1255-4713

First Posted:

Aug 10, 2021

Last Update Posted:

Jul 13, 2022

Last Verified:

Jul 12, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 13, 2022