Clinical Trials Register

Summary
EudraCT Number:	2020-001819-24
Sponsor's Protocol Code Number:	EFC16819
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-02-04
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

Czechia - SUKL

A.2

EudraCT number

2020-001819-24

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled, parallel-group Phase 3 study to evaluate the efficacy, safety, and tolerability of SAR440340/REGN3500/itepekimab (anti-IL-33 mAb) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD)

Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 3 s paralelními skupinami hodnotící účinnost, bezpečnost a snášenlivost přípravku SAR440340/REGN3500/itepekimab (anti-IL-33 mAb) u pacientů se středně těžkou až těžkou chronickou obstrukční plicní nemocí (CHOPN)

A.3.1

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

Study to assess the efficacy, safety, and tolerability of SAR440340/REGN3500/itepekimab in chronic obstructive pulmonary disease (COPD) (AERIFY-2)

A.3.2

Name or abbreviated title of the trial where available

AERIFY-2

A.4.1

Sponsor's protocol code number

EFC16819

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1250-2843

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 & Developpement
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-aventis, s.r.o.
B.5.2	Functional name of contact point	www.sanofi.cz
B.5.3	Address:
B.5.3.1	Street Address	Evropská 846/176a
B.5.3.2	Town/ city	Praha 6
B.5.3.3	Post code	160 00
B.5.3.4	Country	Czechia
B.5.4	Telephone number	+420233 086 111
B.5.5	Fax number	+420233 086 224
B.5.6	E-mail	cz-info@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	Itepekimab
D.3.2	Product code	SAR440340
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	Itepekimab
D.3.9.2	Current sponsor code	SAR440340
D.3.9.3	Other descriptive name	REGN3500
D.3.9.4	EV Substance Code	SUB182669
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 Obstructive Pulmonary Disease

E.1.1.1

Medical condition in easily understood language

Chronic Obstructive Pulmonary Disease

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
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

Primary population (former smokers cohort):
• Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPD

E.2.2

Secondary objectives of the trial

Evaluate in former smokers with moderate-to-severe COPD the efficacy of itepekimab compared with placebo on:
- pulmonary function
- occurrence of moderate-or-severe acute exacerbation of COPD (AECOPD)
- occurrence of severe AECOPD
- occurrence of corticosteroid-treated AECOPD
- respiratory symptoms
- Forced Expiratory Volume in 1 second (FEV1) slope
- health-related quality of life (HRQoL) as assessed by St. George's Respiratory Questionnaire (SGRQ)
Evaluate in former smokers with moderate-to-severe COPD the:
- safety and tolerability of itepekimab
- pharmacokinetic (PK) profile of itepekimab
- Immunogenicity to itepekimab
Estimate in current smokers with moderate-to-severe COPD the efficacy of itepekimab compared with placebo on:
- the annualized rate of acute moderate-or-severe AEOPD
- pulmonary function
Estimate in current smokers with moderate-to-severe COPD the:
- safety and tolerability of itepekimab
- PK profile of itepekimab
- immunogenicity to itepekimab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participant must be 40 to 85 years of age inclusive.
- Physician diagnosis of COPD for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition.
- Smoking history of ≥10 pack-years:
-- For former smokers: participants who report that they are not currently smoking and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1A) with an intention to quit permanently.
-- For current smokers: participants who report that they are currently smoking tobacco (participant smoked at least 1 cigarette per day on average during the past 7 days) at Screening (Visit 1A) and who are not currently participating in or planning to initiate a smoking cessation intervention at Screening (Visit 1A) or during Screening period.
- Participants with moderate-to-severe COPD
- Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year prior to Screening in a participant in whom other causes of chronic cough [eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] has been excluded).
- Documented history of high exacerbation risk defined as having had ≥2 moderate or ≥1 severe exacerbations within the year prior to Screening (Visit 1A), with at least 1 exacerbation treated with systemic corticosteroids. At least one exacerbation must have occurred while participants were on their current controller therapy:
-- Moderate exacerbations will be recorded by the Investigator and are defined as acute worsening of respiratory symptoms that requires either systemic corticosteroids (IM, IV, or oral) and/or antibiotics.
-- Severe exacerbations will be recorded by the Investigator and are defined as AECOPD
that require hospitalization or observation for >24 hours in emergency department/urgent care facility.
- Participants with standard of care controller therapy, for ≥3 months prior to Screening (Visit 1A) and at a stable dose of controller therapy for at least 1 month prior to the Screening, including either: inhaled corticosteroid (ICS) + long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA or LAMA + LABA + ICS.
- Body mass index (BMI) ≥18.0 kg/m^2
- Female participant is not pregnant, not breastfeeding, and at least one of the following conditions applies:
-- not a women of child-bearing potential (WOCBP) OR
-- a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
- Current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma.
- For former smokers: Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
For current smokers: vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1A).
- Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening (Visit 1A) that may affect the participant’s participation in the study.
- Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of α-1 anti-trypsin deficiency, or another diagnosed pulmonary disease.
- Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
- Hypercapnia requiring bilevel positive airway pressure (BiPAP).
- Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).
- Prior history of / planned: lung pneumonectomy for any reason, or lung volume reduction procedures (including bronchoscopic volume reduction) for COPD. Note: Surgical biopsy, or segmentectomy, or wedge resection, or lobectomy for other diseases would not be excluded.
- Unstable ischemic heart disease, including acute myocardial infarction within the past 1 year prior to Screening, or unstable angina in the 6 months prior to Screening (Visit 1A).
- Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.
- Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of anti-hypertensive therapy).
- Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening (Visit 1A).
- History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1A).
- Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or in contact with known exposure to COVID-19 at Screening (Visit 1A); known history of COVID-19 infection within 4 weeks prior to Screening (Visit 1A); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening (Visit 1A); participants who have had a COVID-19 infection prior Screening (Visit 1A) who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
- Evidence of acute or chronic infection requiring systemic treatment with anti bacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medications within 4 weeks before Screening (Visit 1A), significant viral infections within 4 weeks before Screening (Visit 1A) that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).
- Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis.
- History of malignancy within 5 years before Screening (Visit 1A), except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
- Previous use of itepekimab.

E.5 End points

E.5.1

Primary end point(s)

Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) in former smokers ; Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) over the 52-week placebo-controlled treatment period

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline up to Week 52

E.5.2

Secondary end point(s)

1 - Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at Week 52 in former smokers ; FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer
2 - Change from baseline in post-BD FEV1 at Week 52 in former smokers ; FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer
3 - Change from baseline in pre-BD FEV1 at Week 24 in former smokers ; FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer
4 - Time to first moderate or severe AECOPD in former smokers ; Time to first moderate or severe AECOPD over the 52 week placebo-controlled treatment period
5 - Annualized rate of severe AECOPD in former smokers ; Annualized rate of severe AECOPD over the 52 week placebo-controlled treatment period
6 - Time to first severe AECOPD in former smokers ; Time to first severe AECOPD over the 52-week placebo-controlled treatment period
7 - Annualized rate of corticosteroid-treated AECOPD in former smokers ; Annualized rate of corticosteroid-treated AECOPD over the 52-week placebo-controlled treatment period
8 - Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score at Week 52 in former smokers ; The E-RS: COPD is administered as a part of the 14-item EXACT questionnaire and is completed on a daily basis.The 11-item E-RS:COPD assesses severity of respiratory symptoms overall and severity of individual symptoms such as breathlessness, cough and sputum, and chest symptoms The total score of E-RS:COPD ranges from 0 to 40, with higher values indicating more severe respiratory symptoms.
9 - Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) after 4-12 weeks in former smokers
10 - Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score at Week 52 in former smokers ; The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
11 - Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 52 in former smokers ; The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
12 - Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent treatment discontinuation in former smokers
13 - Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities in former smokers
14 - Functional itepekimab concentrations in serum in former smokers
15 - Incidence of treatment-emergent anti-itepekimab antibodies responses in former smokers
16 - Annualized rate of moderate or severe AECOPD in current smokers ; Annualized rate of moderate or severe AECOPD over the 52 week placebo-controlled treatment period
17 - Change from baseline in pre-BD FEV1 at Week 52 in current smokers ; FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer
18 - Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation in current smokers
19 - Incidence of potentially clinically significant laboratory, vital signs, and ECGs abnormalities in current smokers
20 - Functional itepekimab concentrations in serum in current smokers
21 - Incidence of treatment-emergent anti-itepekimab antibodies responses in current smokers

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 8, 10, 11 : Baseline to Week 52
3 : Baseline to Week 24
4, 6 : Baseline through Week 52
5, 7, 9, 16, 17 : Baseline up to Week 52
12, 13, 14, 15, 18, 19, 20, 21 : Baseline up to end of study (Week 72)

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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)

E.8.2.2

Placebo

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

Brazil

Canada

India

Israel

Japan

Korea, Republic of

Mexico

Russian Federation

South Africa

Turkey

United States

Bulgaria

Denmark

France

Germany

Hungary

Netherlands

Norway

Poland

Portugal

Spain

United Kingdom

Czechia

Argentina

E.8.7

Trial has a data monitoring committee

Yes

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:

1150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1150

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

760

F.4.2.2

In the whole clinical trial

2300

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

2021-02-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-16

P. End of Trial
P.	End of Trial Status	Ongoing

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