Clinical Trials Register

Summary
EudraCT Number:	2017-001272-40
Sponsor's Protocol Code Number:	CQAW039A2317
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-01-20
Trial results	View 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

2017-001272-40

A.3

Full title of the trial

A 12-week, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of QAW039 when added to standard-of-care asthma therapy in patients with uncontrolled asthma

Studio multicentrico randomizzato in doppio cieco
controllato verso placebo della durata di 12 settimane per
valutare l¿efficacia e la sicurezza di QAW039 quando
aggiunto alla terapia standard per l¿asma in pazienti con
asma non controllato

A.3.1

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

Study of efficacy and safety of QAW039 when added to standard-of-care asthma therapy in patients with uncontrolled asthma

Studio di efficacia e sicurezza di QAW039 quando
aggiunto alla terapia standard per l¿asma in pazienti con asma non controllato

A.3.2

Name or abbreviated title of the trial where available

ZEAL

A.4.1

Sponsor's protocol code number

CQAW039A2317

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN12345678

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT12345678

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1234-1234-1234

A.5.4

Other Identifiers

Name:

QAW039A

Number:

QAW039A

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	NOVARTIS PHARMA AG
B.1.3.4	Country	Switzerland
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	Novartis
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farma
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio (VA)
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390296541
B.5.5	Fax number	+39029659066
B.5.6	E-mail	info.studiclinici@novartis.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	Fevipiprant
D.3.2	Product code	QAW039
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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	VENTOLIN - 100 MCG SOSPENSIONE PRESSURIZZATA PER INALAZIONE1 CONTENITORE SOTTO PRESSIONE 200 EROGAZIONI
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	salbutamolo
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Pressurised inhalation, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	No
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

Asma

E.1.1.1

Medical condition in easily understood language

Asthma

Asma

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
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 demonstrate the efficacy of QAW039 150 mg once daily as measured by change from baseline in pre-dose FEV1 [in liters], compared with placebo, at the end of the 12-week active-treatment period.

Determinare l¿efficacia di QAW039 150mg somministrato una volta al giorno, misurando il cambiamento rispetto al basale del FEV1 pre-dose (in litri), rispetto al placebo, alla fine delle 12 settimane di trattamento

E.2.2

Secondary objectives of the trial

1. To demonstrate the efficacy of QAW039 150 mg once daily, compared with placebo, on daytime asthma symptoms over the 12-week active-treatment period.
2. To demonstrate the efficacy of QAW039 150 mg once daily, compared with placebo, on total daily short-acting ¿-agonist (SABA) use over the 12-week active-treatment period.
3. To demonstrate the efficacy of QAW039 150 mg once daily, compared with placebo, on change from baseline in Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) scores at the end of the
12-week active-treatment period.
4. To assess the safety of QAW039 150 mg once daily, compared with placebo, with respect to adverse events (AEs), electrocardiograms (ECGs), vital signs and laboratory tests.

1. Dimostrare l¿efficacia di QAW039 150mg somministrato una volta al giorno, rispetto al placebo, in termini di sintomi diurni durante le 12 settimane di trattamento.
2. Dimostrare l¿efficacia di QAW039 150mg somministrato una volta al giorno, rispetto al placebo, in termini di utilizzo dell¿¿-agonista a breve durata d¿azione (SABA) durante le 12 settimane di trattamento.
3. Dimostrare l¿efficacia di QAW039 150mg somministrato una volta al giorno, rispetto al placebo, in termini di cambiamento rispetto al basale del punteggio dell¿Asthma Quality of Life Questionnaire per soggetti con 12 anni o pi¿ vecchi (AQLQ+12) alla fine delle 12 settimane di trattamento.
4. Valutare la sicurezza di QAW039 150mg somministrato una volta al giorno, rispetto al placebo, in termini di eventi avversi (AEs), elettrocardiogramma (ECGs), segni vitali e esami laboratoristici

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-A diagnosis of asthma (according to GINA 2016) for a period of at least 6 months.
-Treated with medium dose inhaled corticosteroid (ICS), or high dose ICS, or low dose ICS plus long-acting beta agonist (LABA), or low dose ICS plus leukotriene receptor antagonist (LTRA), or medium dose ICS plus LABA for at least 3 months prior to Visit 1 and the doses have been stable for at least 4 weeks prior to Visit 1.
-FEV1 of =85% for patients aged =18 years. FEV1 of =90% for patients aged 12 to <18 years.
-Daytime asthma symptom score (0 to 6 scale) of =1 per day during 4 of the last 7 days of the placebo run-in period.
-Total daily SABA use =1 puff per day during 4 of the last 7 days of the placebo run-in period.
-Demonstrated reversible airway obstruction.
-Asthma control questionnaire (ACQ) score = 1.5.

¿ I pazienti devono avere una diagnosi di asma (secondo le GINA2016) da almeno 6 mesi prima di Visita 1.
¿ I pazienti devono essere in trattamento con:
o Dose media di ICS o,
o Alta dose di ICS o,
o Bassa dose di ICS più un ß-agonista a lunga durata d’azione (LABA) o,
o Bassa dose di ICS più un agonista del recettore dei leucotrieni (LTRA) o,
o Dose media di ICS più LABA,
per almeno 3 mesi prima di Visita 1 e la dose deve essere stabile da almeno 4 settimane prima di Visita 1.
¿ FEV1 = 85% rispetto al valore normale del predetto, dopo interruzione dei broncodilatatori a Visita 1 e Visita 101 per i pazienti di età = 18 anni. FEV1 = 90% rispetto al valore normale del predetto dopo interruzione dei broncodilatatori a Visita 1 e Visita 101 per i pazienti di età = 12 anni e < 18 anni.
¿ Pazienti con punteggio (range da 0 a 6) per sintomi diurni = 1 al giorno per 4 dei 7 giorni del periodo placebo del Run-in.
¿ Pazienti che facciano uso giornalmente di = 1 puff di SABA nei 4 dei 7 giorni del periodo placebo del Run-in.
¿ Dimostrare la reversibilità dell’ostruzione delle vie aeree refertata dal central reader della agenzia che fornisce lo spirometro a Visita 1 o a Visita 101. Il test di reversibilità è definito come un aumento del FEV1 di = 12% e = 200ml approssimativamente 15-30 minuti dopo l’inalazione di 400µg si salbutamolo/albuterolo (o equivalenti). E’ permesso l’uso di un distanziatore per la somministrazione di salbutamolo/albuterolo (o equivalente) solo durante il test di reversibilità. Il ricercatore o un suo delegato potrà decidere se usare o no il distanziatore.
o Se non viene dimostrata la reversibilità a Visita 1 , la reversibilità potrà essere ritentata a Vista 101. Se anche a Visita 101 non verrà dimostrata la reversibilità, è possibile riprovare una sola volta nei 4 giorni dopo Visita 101 durante una visita ad hoc.
La reversibilità a Visita 1 o Visita 101 o la singola riprova verrà valutata da un central reader e bisognerà attendere tale revisione prima della randomizzazione.
¿ Un punteggio dell’Asthma Control Questionnaire (ACQ) = 1.5 a Visita 199
.

E.4

Principal exclusion criteria

-Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer.
-A resting QTcF (Fridericia) =450 msec (male) or =460 msec (female).
-Pregnant or nursing (lactating) women.
-Serious co-morbidities.
-Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, or >2 mg of pitavastatin.

¿ Utilizzo di altri farmaci sperimentali entro 5 emivite dall’arruolamento, o entro 30 giorni fino a che l’effetto farmacodinamico atteso è ritornato al basale, a seconda di quale dei due periodi di tempo è più lungo.
¿ Pazienti con un QTcF (Fridericia) a riposo = 450 msec (uomini) o = 460 msec (donne) alla Visita 1.
¿ Pazienti con anamnesi di patologia maligna di qualsiasi organo (ad eccezione del carcinoma delle cellule basali localizzate della cute o del cancro cervicale in situ), trattata o non trattata, nei 5 anni precedenti, indipendentemente dal fatto che ci siano prove di recidive lovali o metastasi.
¿ Donne in gravidanza o allattamento, con la gravidanza definita come lo stato di una donna dopo il concepimento e fino al termine della gestazione, confermata da un test di laboratorio positivo per la gonadotropina corionica umana (hCG).
¿ Donne potenzialmente fertili, definite come tutte le donne fisiologicamente in grado di iniziare una gravidanza, a meno che non utilizzino metodi contraccettivi efficaci durante la somministrazione del trattamento in studio.
¿ Pazienti che presentano un’anormalità di laboratorio clinicamente significativa nei test di laboratorio effettuati a Visita 1.
¿ Pazienti con serie co-morbilità comprese, ma non limitate a, patologie neurodegenerative, artrite reumatoide e altre patologie autoimmuni.
¿ Pazienti in trattamento con simvastatina >20mg, atorvastatina >40mg, pravastatina >40mg o pitavastatina > 2mg. Tali statine a dosi inferiori o uguali a quelle sopra riportate o altre statine saranno permesse durante lo studio.
¿ Pazienti in trattamento con rifampicina, probenecid, ritonavir e acido valproico cioè farmaci che bloccano diversi vie importanti per l’eliminazione di QAW039 (inibizione ad ampia gamma di glucuronisil transferasi uridin difosfato (UTG) e/o inibizione del trasportatore anionico organico 3 (OAT3), del trasportatore organico anionico P1B3 (OATP1B3), proteina per la resistenza multi-xenobiotica (MXR) e p-glicoproteina (P-gp)).
¿ Pazienti in trattamento con qualsiasi statina con un livello CK > 2 x ULN (limite superiore di normalità) alla Visita 1.
¿ Pazienti con storia di condizioni diverse dall’asma che potrebbero portare ad un’elevata eosinofilia (i.e. sindromi ipereosinofiliche, Sindrome di Churg-Strauss, esofagite eosinofila). Pazienti che hanno avuto una infestazione parassitaria nei 6 mesi precedenti a visita 1 sono anch’essi esclusi.

E.5 End points

E.5.1

Primary end point(s)

-Pre-dose Forced Expiratory Volume in 1 second (FEV1) (L)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

E.5.2

Secondary end point(s)

- Daytime asthma symptom score
- Short-acting beta agonist (SABA) taken per day
- Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) score

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks

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

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)

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

Information not present in EudraCT

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

Bulgaria

Canada

Colombia

India

Israel

Italy

Korea, Democratic People's Republic of

Peru

Romania

Sweden

United States

Viet Nam

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: 11-Jun-2019

LVLS: 11-06-2019

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:

455

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

130

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

129

F.4.2.2

In the whole clinical trial

650

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)

At sites participating in the ongoing safety study, completers of this study may be offered participation. Otherwise patients will enter the follow-up period and will not be given further access to study drug because the risk/benefit ratio will not yet have been substantiated and there are marketed therapeutic alternatives available to these patients. At the time of study completion or early termination, all patients will be given appropriate asthma treatment as prescribed by the investigator.

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

2018-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-08-01

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