Clinical Trials Register

Summary
EudraCT Number:	2015-003172-67
Sponsor's Protocol Code Number:	CQAW039A2314
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-10-15
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

Spain - AEMPS

A.2

EudraCT number

2015-003172-67

A.3

Full title of the trial

A 52-week, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of QAW039 when added to existing asthma therapy in patients with uncontrolled severe asthma.

Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo de 52 semanas de duración para evaluar la eficacia y la seguridad de QAW039 añadido al tratamiento existente para el asma en pacientes con asma grave no controlada.

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 in patients with severe asthma inadequately controlled with standard of care asthma treatment.

Estudio para evaluar la eficacia y la seguridad de QAW039 en pacientes con asma grave no controlada añadido al tratamiento existente para el asma .

A.4.1

Sponsor's protocol code number

CQAW039A2314

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 Farmaceutica, S.A.
B.1.3.4	Country	Spain
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 Pharma Services AG
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 Farmaceutica, S.A.
B.5.2	Functional name of contact point	Departamento Medico (ICRO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034900353036
B.5.5	Fax number	0034932479903
B.5.6	E-mail	eecc.novartis@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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fevipiprant
D.3.9.1	CAS number	872365-14-5
D.3.9.2	Current sponsor code	QAW039
D.3.9.3	Other descriptive name	QAW039-NXA.001
D.3.9.4	EV Substance Code	SUB32073
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	150
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	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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fevipiprant
D.3.9.1	CAS number	872365-14-5
D.3.9.2	Current sponsor code	QAW039
D.3.9.3	Other descriptive name	QAW039-NXA.001
D.3.9.4	EV Substance Code	SUB32073
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	450
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.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
D.8 Placebo: 2
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	18.1
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

In patients with severe asthma and high eosinophil counts (?250 cells/?l) receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch.
In patients with severe asthma receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch.

En pacientes con asma grave y recuentos de eosinófilos altos (? 250 células/µl) que reciben tratamiento estándar (SOC) para el asma, demostrar la eficacia (medida según la tasa de exacerbaciones asmáticas de moderadas a graves) de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, al final de la fase de tratamiento activo de 52 semanas.
En pacientes con asma grave que reciben tratamiento estándar (SOC) para el asma, demostrar la eficacia (medida según la tasa de exacerbaciones asmáticas de moderadas a graves) de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, al final de la fase de tratamiento activo de 52 semanas.

E.2.2

Secondary objectives of the trial

In patients with severe asthma and high eosinophil counts (?250 ells/?l) receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in AQLQ+12 scores, ACQ-5 score and pre-dose FEV1.

In all patients with severe asthma receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in : AQLQ+12 scores , ACQ-5 score and pre-dose FEV1.

To assess the safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, with respect to adverse events, ECGs, vitals
sign, laboratory tests and hypersensitivity reactions.

En pacientes con asma grave y recuentos de eosinófilos altos (? 250 células/µl) que reciben tratamiento estándar para el asma demostrar la eficacia de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, en relación con el cambio respecto a la basal en la puntuación del AQLQ+12, ACQ-5 y valor FEV1 pre-dosis al final de la fase de tratamiento activo de 52 semanas.
En todos los pacientes con asma grave que reciben tratamiento estándar para el asma demostrar la eficacia de al menos un nivel de dosis de QAW039 (150 o 450 mg una vez al día), en comparación con placebo, en relación con el cambio respecto a la basal en la puntuación del AQLQ+12, ACQ-5 y valor FEV1 pre-dosis al final de la fase de tratamiento activo de 52 semanas.
Evaluar la seguridad de QAW039, en comparación con placebo, respecto a los acontecimientos adversos, electrocardiogramas (ECG), constantes vitales, pruebas analíticas y reacciones de hipersensibilidad.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Written informed consent.
-Male and female patients aged ?12 years.
-A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.
-Evidence of airway reversibility or airway hyper-reactivity.
-FEV1 of ?40% and ?80% of the predicted normal value.
-An ACQ score ?1.5.
-A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.

Other inclusion criteria apply. See protocol for full details

?Consentimiento informado por escrito
?Pacientes adultos de ambos sexos ? 12 años de edad.
?Diagnostico de asma grave, no controlada en tratamiento segun los pasos 4/5 GINA 2015
?Evidencia de reversibilidad o hiperreactividad de las vías respiratorias
?FEV1 ? 40 % y ? 80 % del valor teórico normal
?ACQ ? 1,5
?Antecedentes de 2 o más exacerbaciones asmáticas durante los 12 meses anteriores a la visita 1
Para el resto de criterios de inclusion, refierase al protocolo.

E.4

Principal exclusion criteria

-Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer.
-Subjects who have participated in another trial of QAW039.
-A QTcF (Fridericia) ?450 msec (male) or ?460 msec (female).
-History of malignancy with the exception of local basal cell carcinoma of the skin.
-Pregnant or nursing (lactating) women.
-Serious co-morbidities.
-Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, and >2 mg of pitavastatin

Other exclusion criteria apply. See protocol for full details

?Uso de cualquier otro fármaco en investigación dentro de un tiempo de 5 vidas medias de la inclusión o 30 días hasta que el efecto farmacodinámico previsto vuelva a los valores basales (aquel periodo que sea más largo).
?Sujetos que hayan participado en otro ensayo de QAW039
?QTcF (Fridericia) ? 450 ms (hombres) o ? 460 ms (mujeres)
?Pacientes con antecedentes de tumores malignos en cualquier órgano, a excepción de carcinoma cutáneo de células basales localizado.
?Mujeres embarazadas o en periodo de lactancia
?Pacientes con comorbilidades graves
?Pacientes que reciban >20 mg de simvastatina, > 40 mg de atorvastatina, >40 mg de pravastatina o >2 mg de pitavastatina
Para el resto de criterios de exclusión, refierase al protocolo.

E.5 End points

E.5.1

Primary end point(s)

Reduction in the rate of moderate-to-severe asthma exacerbations. A severe asthma exacerbation is defined as treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours); or death due to asthma. A moderate asthma exacerbation is defined as treatment with ?rescue? systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).

Reducción en la tasa de exacerbaciones de asma de moderadas a graves. Una exacerbación asmática grave se define como el ratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días y hospitalización; o el tratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días y visita a urgencias (más de 24 horas); o muerte debida al asma. Una exacerbación asmática moderada se define como tratamiento con corticosteroides sistémicos «de rescate» durante al menos 3 días con visita ambulatoria o visita a urgencias (de un máximo de 24 horas).

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

52 semanas

E.5.2

Secondary end point(s)

- Change from baseline in AQLQ+12 score. AQLQ+12 consists of 32 questions each scaled from 1 to 7, where 1 indicates maximal impairment and 7 indicates no impairment.
- Change from baseline in ACQ-5 score. The ACQ- 5 consists of 5 questions on a 7-point scale (0=no impairment, 6=maximum impairment).
- Change from baseline in pre-dose FEV1 (liters).
- Adverse event monitoring.

- Cambio respecto a la basal en la puntuación del AQLQ+12. El AQLQ+12 comprende un total de 32 preguntas individuales y cada ítem puntúa en una escala de 1 a 7 (7 = ningún deterioro; 1 = grave deterioro).
- Cambio respecto a la basal en la puntuación delACQ-5. El ACQ-5 consiste en 5 preguntas con una escala de 7 puntos (0 = ninguna afectación, 6 = afectación máxima).
- Cambio respecto a la basal en el valor FEV1 pre-dosis (litros)
- seguimiento efectos adversos

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

52 semanas

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

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

Argentina

Canada

Czech Republic

Greece

India

Israel

Japan

Korea, Democratic People's Republic of

Malaysia

Mexico

Netherlands

Russian Federation

Serbia

Slovakia

South Africa

Spain

Taiwan

United States

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: 15-November-2018

Ultima visita del ultimo paciente: 15-Nov-2018

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

127

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

127

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

709

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

263

F.4.2.2

In the whole clinical trial

846

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)

Patients completing the treatment period will not be given further access to study drug because the risk/benefit ratio will not yet have been substantiated and there are already other marketed therapeutic alternatives available to treat these patients. At the time of study completion or early termination, all patients will be placed on the appropriate asthma treatment as prescribed by the investigator.

Los pacientes que finalicen el periodo de tratamiento no volverán a tener acceso al fármaco del estudio debido a que por el momento no se ha confirmado la relación beneficio/riesgo y existen otras alternativas terapéuticas comercializadas para tratar a esos pacientes. Cuando finalice el estudio o en caso de finalización prematura, a los pacientes se les asignará el tratamiento apropiado para el asma prescrito por el investigador.

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

2015-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-08-02

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