Clinical Trials Register

Summary
EudraCT Number:	2018-002498-23
Sponsor's Protocol Code Number:	ESR-16-12340
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-002498-23

A.3

Full title of the trial

The Role of Benralizumab on airway Remodeling Assessed by HRCT in severe asthma (BREATH Study)

Il ruolo del Benralizumab sul rimodellamento delle vie aeree nell'asma grave valutato tramite HRCT (Studio BREATH)

A.3.1

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

The Role of Benralizumab on airway Remodeling Assessed by HRCT in severe asthma (BREATH Study)

Il ruolo del Benralizumab sul rimodellamento delle vie aeree nell'asma grave valutato tramite HRCT (Studio BREATH)

A.3.2

Name or abbreviated title of the trial where available

BREATH Study

Studio BREATH

A.4.1

Sponsor's protocol code number

ESR-16-12340

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	AZIENDA OSPEDALIERA UNIVERSITARIA POLICLINICO “PAOLO GIACCONE” DI PALERMO
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Astrazeneca
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Nicola Scichilone A.O. Universitaria Policlinico Paolo Giaccone
B.5.2	Functional name of contact point	PI
B.5.3	Address:
B.5.3.1	Street Address	Via Liborio Giuffrè, 13
B.5.3.2	Town/ city	Palermo
B.5.3.3	Post code	90127
B.5.3.4	Country	Italy
B.5.4	Telephone number	+393393750926
B.5.6	E-mail	nicola.scichilone@unipa.it

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	FASENRA
D.3.2	Product code	[MEDI-563]
D.3.4	Pharmaceutical form	Solution for injection
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	Benralizumab
D.3.9.1	CAS number	1044511-01-4
D.3.9.2	Current sponsor code	MEDI-563
D.3.9.3	Other descriptive name	Benralizumab is a humanised monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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
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

SEVERE ASTHMA

ASMA GRAVE

E.1.1.1

Medical condition in easily understood language

SEVERE ASTHMA

ASMA GRAVE

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	LLT
E.1.2	Classification code	10068462
E.1.2	Term	Eosinophilic asthma
E.1.2	System Organ Class	100000004855

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 BENRALIZUMAB TO REDUCE AIRWAY INFLAMMATION AND FEATURE OF AIRWAY REMODELING EVALUATED BY HRCT

VALUTARE L'EFFICACIA DEL BENRALIZUMAB PER RIDURRE L'INFIAMMAZIONE DELLE VIE AEREE E LE CARATTERISTICHE DEL RIMODELLAMENTO DELLE VIE AEREE VALUTATE TRAMITE HRCT

E.2.2

Secondary objectives of the trial

1. to assess wthether the effect of Benralizumab on HRCT markers of remodeling parallels the improvement in the disease, assessed by a reduction in the frequency and severity of respiratory symptoms as well as rate and seveity of exacerbations.
2. to assess wthether the effect of Benralizumab on biomarkers of airways inflammation (exhaled bronchial and alveolar nitric oxide (NO) concentrations and blood and sputum eosinophils levels) parallels the improvement in the control of the disease, assessed by a reduction in the frequency and severity of respiratory symptoms as well as rate and seveity of exacerbations.

1. Valutare tramite HRCT se l’effetto del Benralizumab sui marcatori di rimodellamento corrisponda ad un miglioramento del controllo della malattia, in termini di riduzione della severità e della frequenza dei sintomi respiratori così come in termini di percentuale e gravità delle riacutizzazione
2. Valutare se gli effetti del Benralizumab sui marcatori dell’infiammazione delle vie aeree (concentrazioni di ossido nitrico (NO) esalato bronchiale e alveolare e livelli di eosinofili nell’espettorato e nel sangue) corrisponda ad un miglioramento nel controllo della malattia in termini di riduzione della severità e della frequenza dei sintomi respiratori così come in termini di percentuale e gravità delle riacutizzazione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female with age over 18 yrs.
2. Clinical diagnosis of persistent asthma for at least 6 months, according to GINA guidelines;
3. Existing treatment with high dose inhaled corticosteroids (ICS>500 mcg total daily dose of fluticasone propionate) in combination with other 2 controllers (LABA, LAMA, LTRA) for at least 3 months.
4. Positive methacholine challenge test (PC20 FEV1< 4mg/ml or PD20 FEV1<0.8 mg) or positive response to the spirometry with reversibility test in the previous year; reversibility test is positive if the pre-salbutamol FEV1 increases more than 200 mL and 12%, 15 min after the administration of 400 mg of salbutamol.
5. A forced expiratory volume in 1 second (FEV1<80% of predicted normal during the screening period);
6. History of 2 or more exacerbations in the previous year requiring systemic corticosteroids;
7. Blood eosinophil count of at least 300 cells per mcL.
8. Motivation to complete all the study visits and procedure, and ability to communicate well with the investigator and be capable of understanding the nature of the research.
9. Ability to comprehend and complete questionnaires on respiratory symptoms.
10. Written informed consent.

1) Uomini o donne di età superiore ai 18 anni;
2) Diagnosi di asma persistente secondo le linee-guida GINA da almeno 6 mesi;
3) Esistente trattamento con alta dose di corticosteroidi inalati (ICS>500 mcg dose giornaliera di fluticasone propionato) in combinazione con altri due controller (LABA, LAMA, LTRA) da almeno 3 mesi.
4) Positività al test della metacolina (PC20 FEV1<4mg/ml o PD20 FEV1<0.8 mg) o test di reversibilità nell’anno precedente; il test di reversibilità sarà positivo se il FEV1 pre-salbutamolo aumenta più di 200 mL e del 12%, 15 minuti dopo la somministrazione di 400 mg di salbutamolo.
5) Volume espiratorio forzato ad 1 secondo (FEV1<80% del predetto durante il periodo di screening);
6) Storia di 2 o più esacerbazioni nell’anno precedente che abbiano necessitato del ricorso a corticosteroidi sistemici;
7) Conta eosinofilia di almeno 300 cellule per mcL
8) Motivazione a completare tutte le visite e procedure previste dallo studio, abilità nel comunicare con lo sperimentatore, capacità di comprendere la natura dello studio;
9) Abilità nel comprendere e completare i questionari relativi ai sintomi respiratori
10) Consenso informato scritto.

E.4

Principal exclusion criteria

1. Inability to carry out pulmonary function testing;
2. Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary disease (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), cardiovascular diseases (cardiac arrhythmia, unstable angina, congestive heart failure, aneurysm), neurological or haematological autoimmune diseases;
3. Malignancy;
4. Any chronic diseases with prognosis < 2 years;
5. Pregnant or lactating females or not able to exclude pregnancy during the study period;
6. History of alcohol or drug abuse;
7. Current smoker with a smoking history >10 pack-years;
8. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
9. Patients who are participating to other clinical studies.
10. Impaired DLCO suggestive of diseases other than asthma (i.e. Emphysema).
11. A helminth parasitic infection within 24 weeks that has not been treated with, or has failed to respond to, standard of care therapy

1) Incapacità di effettuare i test di funzionalità respiratoria;
2) Comorbidità instabili o clinicamente significative: ipertiroidismo non-controllato, insufficienza epatica importante, malattia polmonare scarsamente controllata (tubercolosi, micosi polmonare), malattia gastrointestinale (ulcera peptica attiva), malattia cardiovascolare ( aritmia cardiaca, angina instabile, scompenso cardiaco congestizio, aneurisma), malattia neurologica o ematologica autoimmune;
3) Tumore;
4) Qualsiasi malattia cronica con prognosi < 2 anni;
5) Donne in gravidanza o allattamento o non in grado di escludere una gravidanza durante il periodo di studio;
6) Storia di abuso di alcool o droga;
7) Attuali fumatori con una storia di fumo>10 anni;
8) Pazienti che non hanno la volontà di aderire al protocollo o non sono in grado di comprendere la natura, lo scopo e le possibili conseguenze dello studio;
9) Pazienti che stanno partecipando ad altri studi clinici;
10) DLCO alterata indicativa di malattia differente dall’asma (es. enfisema)
11) Parassitosi da elminti da 24 settimane non trattata o non responsiva al trattamento.

E.5 End points

E.5.1

Primary end point(s)

To reduce number of exacerbations and symptoms of severe asthma

Riduzione delle esacerbazioni e dei sintomi respiratori dell'asma grave

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

52 settimane

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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

Yes

E.8.1.7.1

Other trial design description

Studio monocentrico, randomizzato, in doppio cieco, controllato con placebo, longitudinale

Single-center, randomized, double-bind, placebo-controlled, longitudinal, parallel group study

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

follow up phone contact every 8 weeks

phone contact periodico ogni 8 settimane

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

2019-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-17

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

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