Clinical Trials Register

Summary
EudraCT Number:	2021-000829-27
Sponsor's Protocol Code Number:	LPS16747
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-07-26
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-000829-27

A.3

Full title of the trial

A randomized, double-blind, head-to-head comparison of dupilumab versus omalizumab in severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and comorbid asthma patients

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

EVEREST: EValuating trEatment RESponses of dupilumab versus omalizumab in Type 2 patients

A.3.2

Name or abbreviated title of the trial where available

EVEREST

A.4.1

Sponsor's protocol code number

LPS16747

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1255-4713

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-aventis Recherche & Développement
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi Sp. z o.o.
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	ul. Marcina Kasprzaka 6
B.5.3.2	Town/ city	Warszawa
B.5.3.3	Post code	01-211
B.5.3.4	Country	Poland
B.5.4	Telephone number	+482228 00 000
B.5.6	E-mail	informacja.medyczna@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dupilumab
D.3.2	Product code	SAR231893
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dupilumab
D.3.9.2	Current sponsor code	SAR231893
D.3.9.3	Other descriptive name	REGN668
D.3.9.4	EV Substance Code	SUB88511
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xolair
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Omalizumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OMALIZUMAB
D.3.9.1	CAS number	242138-07-4
D.3.9.4	EV Substance Code	SUB12543MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xolair
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Omalizumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OMALIZUMAB
D.3.9.1	CAS number	242138-07-4
D.3.9.4	EV Substance Code	SUB12543MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic rhinosinusitis with nasal polyps

E.1.1.1

Medical condition in easily understood language

Chronic rhinosinusitis with nasal polyps

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	27.0
E.1.2	Level	PT
E.1.2	Classification code	10080060
E.1.2	Term	Chronic rhinosinusitis with nasal polyps
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

-To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell

E.2.2

Secondary objectives of the trial

- 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 safety of dupilumab and omalizumab

E.2.3

Trial contains a sub-study

E.3

Principal 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 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 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 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.

E.4

Principal exclusion criteria

- 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).

E.5 End points

E.5.1

Primary end point(s)

1 - 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).
2 - 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.

E.5.1.1

Timepoint(s) of evaluation of this end point

1, 2 - Baseline to Week 24

E.5.2

Secondary end point(s)

1 - 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').
2 - Change from baseline to Week 24 in the NC score of the CRSwNP
Nasal Symptom Diary ; NC scores are scored from 0 ('No symptoms') to
3 ('Severe symptoms').
3 - 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
4 - Change from baseline to Week 24 in 22-Item Sinonasal
Outcome
Test (SNOT-22) total score ; SNOT-22 is a patient-reported outcome
(PRO) questionnaire. Score ranges from 0 to 110 with higher score
indicating greater rhinosinusitis related health burden.
5 - 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.
6 - Change from baseline to Week 24 in Nasal Peak Inspiratory Flow
(NPIF) ; Nasal Peak Inspiratory flow (nasal flow in liter per minute)
7 - Change from baseline to Week 24 in rhinosinusitis VAS ; Severity of
the rhinosinusitis from 0 to 10. Higher scores indicate more severe
symptom.
8 - Incidence of treatment-emergent adverse events (TEAEs) and serious
adverse events (SAEs) ; Incidence of treatment-emergent adverse
events (TEAEs) and serious adverse events (SAEs)
9 - Incidence of adverse events of special interest (AESIs) ; Incidence of
adverse events of special interest (AESIs)

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3, 4, 5, 6, 7 - Baseline to Week 24
8, 9 - Baseline to Week 36

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United Kingdom

United States

Belgium

Czechia

Denmark

Finland

France

Germany

Hungary

Italy

Poland

Portugal

Romania

Spain

Sweden

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

800

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

662

F.4.2.2

In the whole clinical trial

844

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-12-27

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