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    Summary
    EudraCT Number:2014-005084-32
    Sponsor's Protocol Code Number:D6230C00001
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-08-05
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2014-005084-32
    A.3Full title of the trial
    A randomized, double-blind, placebo-controlled, parallel group, multi-centre Phase IIa study in asthma patients comparing the efficacy and safety of once daily inhaled Interferon beta-1a to placebo, administered for 14 days after the onset of symptoms of an upper respiratory tract infection for the prevention of severe exacerbations
    Étude multicentrique de phase IIa, randomisée, en double aveugle, contrôlée contre placebo et en groupes parallèles, comparant l’efficacité et la tolérance d’une dose quotidienne inhalée d’interféron bêta-1a vs placebo, administrée chez des patients asthmatiques pendant 14 jours après l'apparition de symptômes d'une infection des voies respiratoires supérieures pour la prévention des exacerbations sévères
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to investigate if inhaled Interferon beta-1a is safe, and could prevent or reduce the severity of asthma attacks when administered to asthma patients at the onset of a virus affecting their airways (e.g. common cold or influenza)
    Evaluation de l’efficacité et la tolérance de l’interféron bêta-1a inhalé pour la prévention des exacerbations sévères de l’asthme, chez des patients asthmatiques dès l'apparition de symptômes d'une infection virale des voies respiratoires supérieures.
    A.3.2Name or abbreviated title of the trial where available
    INEXAS
    A.4.1Sponsor's protocol code numberD6230C00001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointInformation Centre
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityN/A
    B.5.3.3Post codeN/A
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.centre@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameInterferon beta-1a Nebuliser solution 48 μg/mL
    D.3.2Product code Interferon beta-1a Nebuliser solution 48 μg/mL
    D.3.4Pharmaceutical form Nebuliser solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNInterferon beta-1a
    D.3.9.1CAS number 145258-61-3
    D.3.9.2Current sponsor codeInterferon beta-1a
    D.3.9.3Other descriptive nameIFN beta-1a
    D.3.10 Strength
    D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number48
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboNebulisation solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Asthma
    Asthme
    E.1.1.1Medical condition in easily understood language
    Asthma
    Asthme
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10003553
    E.1.2Term Asthma
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of inhaled Interferon beta-1a compared to placebo in preventing severe exacerbations during the 14 days of treatment following onset of an upper respiratory tract infection in asthmatic patients, on top of their regular asthma maintenance treatment.
    Évaluer l’efficacité de l’interféron bêta-1a inhalé comparé au placebo administré chez des patients asthmatiques pendant 14 jours après l'apparition de symptômes d'une infection des voies respiratoires supérieures pour la prévention des exacerbations sévères, en complément de leur traitement de fond habituel pour le contrôle de l’asthme
    E.2.2Secondary objectives of the trial
    To evaluate the preventive or attenuating effect of inhaled Interferon beta-1a compared to placebo on deterioration of secondary efficacy endpoints during and after upper respiratory tract infection. Analysed variables will include:
    - Occurrence of severe exacerbations with onset during day 1-30 after start of treatment
    - Occurrence of moderate exacerbations with onset during day 1-30 after start of treatment
    - Time to severe exacerbation
    - Time to moderate exacerbation
    - Change from treatment baseline in Patient reported outcomes
    - (a) Asthma control as measured by ACQ-6
    - (b) Day-time and night-time asthma symptom score and night-time awakenings as determined by area under the curve (AUC) over day 1-14
    - (c) Health-related quality of life as measured by AQLQ(S)
    - Day-time and night-time reliever medication use as determined by AUC over day 1-14 as change from the treatment baseline level
    - Lung function, ie morning and evening PEF and FEV1
    Évaluer l’effet préventif ou atténuant de l’interféron bêta-1a inhalé comparé au placebo sur la détérioration des critères secondaires d’efficacité pendant et après une infection des voies respiratoires supérieures:
    -Survenue d’exacerbations sévères et modérées débutant au cours des jours 1 à 30 après le début du traitement
    -Délai de survenue d’une exacerbation sévère ou modérée
    -Modification par rapport au traitement initial des résultats rapportés par le patient:
    .Du contrôle de l’asthme mesuré par ACQ-6
    .Du score des symptômes d’asthme diurnes et nocturnes et des réveils nocturnes, déterminé par l’aire sous la courbe (ASC) entre les jours 1 et 14
    .De la qualité de vie liée à la santé mesurée par AQLQ[S]
    -Modification par rapport au niveau de traitement initial de l’utilisation diurne et nocturne du médicament de secours, déterminée par l’ASC entre les jours 1 et 14
    -Débit expiratoire de pointe (DEP), volume expiratoire maximum par seconde (VEMS) matin et soir
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For inclusion in the study patients should fulfil the following criteria:

    1.Provision of signed and dated written informed consent prior to any study specific procedures

    2.Male or female aged 18 and above at the time of screening

    3.History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250 μg fluticasone dry powder formulation equivalents total daily dose, as defined in GINA 2014; see Appendix Chapter 5) and a second controller medication (eg, LABA or leukotriene receptor antagonist). The medium or high dose ICS plus LABA can be any combination inhaler or 2 separate inhalers. Patients must have taken ICS (>250 μg fluticasone or the equivalent daily) plus second controller medication for at least 12 months prior to the date the informed consent is obtained, with or without another controller such as OCS, theophylline, tiotropium, or leukotriene receptor antagonists

    4.Proof of post-bronchodilator reversibility in FEV1 of ≥12% and ≥200 mL (Pellegrino et al 2005) documented within 5 years prior to Visit 1, or proof of a positive response to a methacholine or histamine challenge (a decrease in FEV1 by 20% [PC20] at ≤8 mg/mL) performed according to ATS/ERS guidelines (American Thoracic Society 2000) documented within 5 years prior to Visit 1. If historical documentation is not available, reversibility or proof of a positive response to a methacholine challenge must be demonstrated and documented at Visit 1

    5.Must answer “Yes” to the question “Does a cold or flu make your asthma worse?”

    6.To have had at least two documented severe asthma exacerbations within the last 24 months that were suspected by the patient to have been caused by a cold or flu
    and
    To have had at least one documented severe asthma exacerbation within the last 12 months that was suspected by the patient to have been caused by a cold or flu

    A severe asthma exacerbation is defined as worsening of asthma symptoms and:

    -Use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least three days and/or

    - An unscheduled visit or emergency room visit due to asthma symptoms that requires at least one dose of systemic corticosteroids and/or

    - An in-patient hospitalization due to asthma requiring at least one dose of systemic corticosteroids

    The below defines what is acceptable to document exacerbations in this study:

    - Discharge summaries from a hospital, emergency department, or an urgent care facility indicating that a subject was hospitalized/treated with systemic steroids for an asthma exacerbation.

    - Signed and dated notes from a referring physician, including information regarding diagnosis and treatment of an exacerbation with systemic steroids.

    -Patients can provide evidence of prescriptions for systemic steroids used during an exacerbation.

    -A documented conversation between the treating/referral physician or nurse/nurse practitioner certifying that a patient was treated for an exacerbation with steroids at their clinic or under their supervision. The dates (month/year) of the exacerbations and verbal confirmation that appropriate prescriptions were provided is necessary. This option should be used only if reasonable attempts to procure patient records have been unsuccessful.

    A combination of the above is acceptable to document the two required exacerbations. However, it is necessary for the Investigator to document how they obtained confirmation of the patient’s asthma exacerbations. It is the Investigator’s responsibility to ensure patient eligibility into the clinical study. In cases where the Investigator feels that alternative records to the above constitutes acceptable documentation, the Study Physician will be contacted for their assessment of eligibility prior to enrolment. Every attempt should be made to obtain appropriate source documentation of medical records.

    7.Negative pregnancy test (urine) for female patients of childbearing potential to communicate well with the Investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits

    9.Ability to read and write and use the electronic devices

    For participation in the optional genetic research

    10.Provision of signed and dated written informed consent for optional genetic research. If a patient declines to participate in the optional exploratory genetic research there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study
    Pour pouvoir être inclus dans l’étude, chaque patient doit satisfaire à la totalité des critères suivants:
    1. Obtention d’un consentement éclairé daté et signé avant toute procédure spécifique de l'étude
    2. Homme ou femme ≥ 18 ans lors de la visite d’enrôlement
    3. Antécédents d’asthme diagnostiqué par un médecin, nécessitant un traitement par CSI à dose modérée à forte (dose quotidienne totale équivalente à > 250 μg de fluticasone en formulation poudre sèche, comme défini dans l'Annexe Chapitre 5 des recommandations GINA 2014) et d’un deuxième traitement de fond (ex. β2-LDA ou antagoniste des récepteurs de leucotriènes). Le traitement par CSI à dose modérée ou forte associé au β2-LDA peut se présenter sous forme d’un inhalateur en association ou sous forme de 2 inhalateurs distincts. Les patients devront avoir pris un traitement par CSI (> 250 μg de fluticasone ou dose journalière correspondante) associé à un deuxième traitement de fond pendant au moins 12 mois avant la date de l’obtention du consentement éclairé, avec ou sans un autre traitement de fond tel que corticoïdes par voie orale, théophylline, tiotropium, ou antagonistes des récepteurs des leucotriènes
    4 Justifier d’une réversibilité du VEMS post-bronchodilatateur ≥ 12 % et ≥ 200 ml documentée au cours des 5 années précédant la Visite 1, ou justifier d’une réponse positive à un test à la méthacholine ou à l’histamine (diminution du VEMS de 20 % [PC20] à ≤ 8 mg/ml) réalisé selon les recommandations ATS/ER, documenté au cours des 5 années précédant la Visite 1. En l’absence de documentation, la réversibilité ou la confirmation d’une réponse positive au test à la méthacholine devra être démontrée et documentée lors de la Visite 1
    5. Réponse «oui» à la question «votre asthme a-t-il été aggravé par un rhume ou une grippe»
    6. Antécédents d’au moins 2 exacerbations sévères de l’asthme documentées dans les 24 derniers mois, suspectées par le patient comme étant dues à un rhume ou à une grippe, et
    Antécédents d’au moins une exacerbation sévère de l’asthme documentée au cours des 12 derniers mois suspectée par le patient comme étant due à un rhume ou à une grippe
    7. Pour les femmes en âge de procréer, test (urinaire) de grossesse négatif, capacité à bien communiquer avec l’investigateur et à comprendre l’objectif de la recherche et son traitement, y compris ses risques et bénéfices
    9 . Capacité à lire, écrire et utiliser les dispositifs électroniques

    Participation à l’étude optionnelle de recherche génétique
    10. Obtention d’un consentement éclairé à la recherche génétique optionnelle. Si un patient refuse de participer à la recherche génétique, il n’en subira aucun préjudice ni perte de bénéfice et ne sera pas exclu d’aucun autre aspect de l'étude principale
    E.4Principal exclusion criteria
    Patients should not enter the study if any of the following exclusion criteria are fulfilled:
    1.Involvement in the planning and/or conduct of the study (applies to both
    AstraZeneca staff and staff at third party vendors or staff at the study sites)
    2.Previous randomization to treatment in the present study
    3.Any condition, including findings in the medical history or in the pre-study assessments that, in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the patient in the study or that could interfere with the study objectives, conduct or evaluation
    4.Lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis)
    5.Patients with ≥4 severe exacerbations during the last 12 months that the patient suspected were triggered by something else than an upper respiratory tract infection
    6.Current participation in another clinical trial or participation in a clinical trial where the patient has received a dose of a test product (IMP) within 12 weeks prior to entry into the study for small molecules and within 12 months prior to entry into the study for biologicals
    7.Patients who currently have, or have had within the past 3 months, any significant underlying medical condition(s) that could impact interpretation of results eg, infections, haematological disease, malignancy, renal, hepatic, coronary heart disease or other cardiovascular disease, including arrhythmias, endocrinological or gastrointestinal disease
    8.Abnormal vital signs, after at least 10 minutes supine rest, defined as any of the following:
    -In patients > 60 years old, systolic blood pressure <90 mmHg or ≥160 mmHg
    -Diastolic blood pressure <50 mmHg or ≥100 mmHg
    -HR <45 or >95 beats per minute
    9.Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, as considered by the Investigator, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology (particularly in the protocol defined primary lead) or left ventricular hypertrophy
    10.Prolonged QTcF >450 ms (for both gender) or shortened QTcF <340 ms or family history of long QT syndrome
    11.PR(PQ) interval shortening <120ms (PR<120 ms but >110 ms is acceptable if there is no evidence of ventricular pre-excitation).
    12.PR(PQ) interval prolongation (>240ms), intermittent second or third degree AV block, or AV dissociation
    13.QRS duration >120ms including persistent or intermittent bundle branch block
    14.Patients with implantable cardiac defibrillator (ICD) or a permanent pacemaker and patients with symptomatic ventricular and / or atrial tachyarrhythmias
    15.Patients with unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society (CSS) class II or a myocardial infarction or stroke within 6 months
    16.History of hospitalization within 12 months caused by heart failure or a diagnosis of heart failure higher than New York Heart Association (NYHA) class II
    17.History of hypersensitivity to natural or recombinant Interferon beta-1a or to any of the drug preparation excipients
    18.Received any marketed biologic agent (eg, omalizumab) within 12 months or 5 times the half-life (whichever is the longer) of the agent prior to enrolment
    19.Significant history of depressive disorder or suicidal ideation. Specifically; individuals with current severe depression (ie, a low mood, which pervades all aspects of life and an inability to experience pleasure in activities that formerly were enjoyed); individuals with a past history of depression that required hospitalization or referral to psychiatric services in the past 5 years; individuals who currently feel suicidal or have attempted suicide in the past
    20.History of epilepsy or seizures after the age of 5 years, other than febrile childhood seizure(s)
    21.History of drug or alcohol abuse within 12 months prior to screening enrolment
    22.Patients who have hepatic serum enzyme levels ≥2.5 times the normal range
    23.Positive test for serum hepatitis B surface antigen, hepatitis C antibody, or HIV
    24.Patients with a smoking history of ≥20 pack-years (1 pack year = 20 cigarettes smoked per day for one year)
    25.Female who is breast-feeding, pregnant (verified by urine dipstick pregnancy test) or intends to become pregnant during the study
    26.Patients who are unable to demonstrate an acceptable spirometry technique
    27.Patients that have previously been included in studies evaluating the investigational medicinal product
    For participation in the optional genetic research
    Any of the following is regarded as a criterion for exclusion from the genetic research:
    28.Previous bone marrow transplant
    29.Non-leukocyte depleted whole blood transfusion within 120 days of the date of the PGx sample collection
    1 Participation à la planification et/ou à la conduite de l’étude (s'applique au personnel d'AstraZeneca, à celui de tout autre fournisseur et celui du centre d’étude)
    2 Randomisation précédente dans la période de traitement de l’étude
    3 Toute affection, y compris les anomalies recueillies dans les antécédents médicaux ou diagnostiquées lors des évaluations effectuées avant l’étude qui, de l’avis de l’investigateur, peut soit entraîner un risque ou une contre-indication pour le patient du fait de sa participation à l’étude, soit interférer avec les objectifs, la conduite ou les évaluations de l’étude
    4 Pathologie pulmonaire autre que l’asthme (ex: bronchopneumopathie chronique obstructive, mucoviscidose, aspergillose bronchopulmonaire allergique)
    5 ≥ 4 exacerbations sévères au cours des 12 derniers mois, suspectées par le patient comme étant déclenchées par un autre facteur qu’une infection des voies respiratoires supérieures
    6 Participation à un autre essai clinique en cours ou pour lequel le patient a reçu une dose de produit expérimental dans les 12 semaines précédant l’entrée dans l’étude pour les petites molécules et dans les 12 mois précédant l’entrée dans l’étude pour toutes biothérapies
    7 Présence ou antécédent(s) de toute anomalie significative au cours des 3 derniers mois qui pourrait interférer avec l’interprétation des résultats de l’étude, par exemple, infections, maladie hématologique, pathologie maligne, rénale, hépatique, cardiopathicoronarienne ou autre maladie cardiovasculaire, y compris arythmies, affections endocriniennes ou gastro-intestinales
    8 Anomalie des signes vitaux, après au moins 10 mn de repos en position allongée, définie comme l’une des situations suivantes:
    -Patients > 60 ans, pression artérielle systolique < 90 mmHg ou ≥ 160 mmHg
    -Pression artérielle diastolique < 50 mmHg ou ≥ 100 mmHg
    -Fréquence cardiaque < 45 ou >95 battements par mn
    9 Toute anomalie cliniquement importante du rythme, de la conduction ou de la morphologie de l’ECG au repos, et toute anomalie de l’ECG à 12 dérivations qui, selon l’investigateur, pourrait interférer avec l’interprétation des variations de l’intervalle QTc, y compris les anomalies de la morphologie du segment ST-onde T (en particulier dans la dérivation principale définie par le protocole) ou une hypertrophie ventriculaire gauche
    10 Allongement de l’intervalle QTcF > 450 ms (pour les deux sexes) ou intervalle QTcF raccourci < 340 ms ou antécédents familiaux d’un syndrome du QT long
    11 Diminution de l’intervalle PR(PQ) < 120 ms (PR< 120 ms; un PR > 110 ms est acceptable s’il n’y a pas de signe de pré-excitation ventriculaire)
    12 Allongement de l’intervalle PR(PQ) (> 240 ms), bloc auriculo-ventriculaire du 2nd degré intermittent ou du 3ème degré ou dissociation auriculo-ventriculaire
    13 Durée de l’intervalle QRS >120 ms y compris bloc de branche persistant ou intermittent
    14 Défibrillateur cardiaque implantable ou stimulateur cardiaque permanent et présence d’une tachyarythmie ventriculaire et/ou auriculaire symptomatique
    15 Angor instable ou angor stable> stade II de la classification de la SCC ou infarctus du myocarde ou accident vasculaire cérébral dans les 6 derniers mois
    16 Hospitalisation dans les 12 mois précédents pour insuffisance cardiaque ou diagnostic d’insuffisance cardiaque > classe II de la classification NYHA
    17 Antécédents d’hypersensibilité à l’interféron bêta-1a naturel ou recombinant, ou à un excipient
    18 Administration de toute biothérapie commercialisée (ex: omalizumab) dans les 12 mois ou les 5 demi-vies (selon la durée la plus longue) avant l’enrôlement
    19 Antécédent significatif de trouble dépressif ou d’idées suicidaires. Spécifiquement: personne présentant actuellement une dépression sévère; antécédents de dépression ayant nécessité une hospitalisation ou l’orientation vers des services psychiatriques au cours des 5 dernières années; personne ayant actuellement des idées suicidaires ou ayant fait des tentatives de suicide dans le passé
    20 Antécédents d’épilepsie ou de convulsions après l’âge de 5 ans, autres que des convulsions hyperthermiques de l’enfance
    21 Antécédents d’alcoolisme ou de toxicomanie dans les 12 mois précédant l’enrôlement
    22 Taux sériques d’enzymes hépatiques ≥ 2,5 fois les valeurs normales
    23 Test positif pour l’antigène de surface de l’hépatite B, l’anticorps de l’hépatite C ou le VIH
    24 Antécédents de tabagisme ≥ 20 paquets-année
    25 Allaitement, grossesse en cours (vérifiée par un test urinaire de grossesse) ou grossesse prévue pendant l’étude
    26 Incapacité à démontrer une technique de mesure spirométrique acceptable
    27 Précédente inclusion dans des études évaluant le médicament à l’étude
    Participation à l’étude optionnelle de recherche génétique
    28 Antécédents de greffe allogénique de moelle osseuse
    29 Transfusion de sang total non déplété en leucocytes, au cours des 120 jours précédant la date du recueil de l’échantillon pour étude génétique
    E.5 End points
    E.5.1Primary end point(s)
    Number of severe exacerbations (during 14 days of treatment)
    Duration of severe exacerbation

    Nombre d’exacerbations sévères (pendant la période de 14 jours de traitement)
    Durée de l’exacerbation sévère
    E.5.1.1Timepoint(s) of evaluation of this end point
    During the 14 days of treatment
    Pendant les 14 jours de traitement
    E.5.2Secondary end point(s)
    Number of moderate exacerbations (during 14 days of treatment)
    Number of severe exacerbations (during day 1-30 after start of treatment)
    Number of moderate exacerbations (during day 1-30 after start of treatment)
    Time to severe exacerbation
    Time to exacerbation (moderate or severe)

    Change from treatment baseline in Patient reported outcomes in the following variables:
    - Asthma control as measured by ACQ-6
    - Day-time and night-time asthma symptom score and night-time awakenings as determined by area under the curve (AUC) over day 1-14
    - Health-related quality of life as measured by AQLQ(S)

    Day-time and night-time reliever medication use as determined by AUC over day 1-14 as change from the treatment baseline level

    Lung function ie, PEF, FEV1
    Morning and evening peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) measured daily at home, as determined by AUC over day 1-14 as change from the baseline level
    Nombre d’exacerbations modérées (pendant la période de 14 jours de traitement)
    Nombre d’exacerbations sévères (débutant au cours des jours 1 à 30 après le début du traitement)
    Nombre d’exacerbations modérées (débutant au cours des jours 1 à 30 après le début du traitement)
    Délai de survenue d’une exacerbation sévère
    Délai de survenue d’une exacerbation (modérée ou sévère)

    Modification, par rapport au traitement initial, des résultats rapportés par le patient pour les variables suivantes :
    - contrôle de l’asthme mesuré par le questionnaire ACQ-6
    - score des symptômes d’asthme diurnes et nocturnes et des réveils nocturnes, déterminé par l’aire sous la courbe (ASC) entre les jours 1 et 14
    - qualité de vie liée à la santé, mesurée par le questionnaire AQLQ[S]

    Modification par rapport au niveau de traitement initial de l’utilisation diurne et nocturne du médicament de secours, déterminée par l’ASC entre les jours 1 et 14

    Fonction pulmonaire : DEP, VEMS
    Variation par rapport au niveau de traitement initial des valeurs de DEP et VEMS du matin et du soir, mesurés au domicile, déterminés par l’ASC entre les jours 1 et 14
    E.5.2.1Timepoint(s) of evaluation of this end point
    During the 14 days of treatment and for some up to 30 days after start of treatment
    Pendant les 14 jours de traitement et jusqu'à 30 jours après le début du traitement
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Colombia
    France
    Korea, Democratic People's Republic of
    Spain
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    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
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 180
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 220
    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
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-01
    P. End of Trial
    P.End of Trial StatusOngoing
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