Resumen

Estudio para investigar si el Interferon beta-1a inhalado es seguro y bien tolerado, y si puede prevenir o reducir la gravedad de las crisis asmáticas cuando se administra a pacientes con asma al inicio de los síntomas de un resfriado común o gripe.

Descripción detallada

El estudio constará de una Fase Previa al Tratamiento seguida de una Fase de Tratamiento. Los pacientes son evaluados en el cribado e ingresan en la fase previa al tratamiento, donde permanecen hasta que desarrollan síntomas de resfriado común o gripe. Durante esta fase previa al tratamiento, se preguntará diariamente a los pacientes si creen que tienen un resfriado común o gripe. Cuando el paciente responda afirmativamente a la pregunta de si está contrayendo un resfriado común o gripe, se toman medidas para evaluar al paciente en el centro del estudio y, si cumple los criterios, ingresa en la Fase de Tratamiento. Se realizan evaluaciones basales y el paciente es aleatorizado 1:1 para recibir 24 μg (dosis medida) de Interferon beta-1a inhalado o placebo una vez al día durante 14 días (administrado mediante el dispositivo I-neb® [Philips Respironics]). El tratamiento debe iniciarse lo antes posible, pero no más tarde de 48 horas tras el inicio del primer síntoma de resfriado común o gripe. Los pacientes serán evaluados en cuanto a exacerbaciones y cambios en los síntomas respiratorios y el uso de medicación de rescate en el domicilio mediante un dispositivo ePRO. La función pulmonar se medirá tanto en el domicilio por los propios pacientes como en el centro del estudio. Habrá cinco visitas clínicas durante la Fase de Tratamiento y dos visitas tras el fin del tratamiento; la eficacia y la seguridad serán monitoreadas hasta 2-3 semanas después del fin del tratamiento, momento en que tendrá lugar una visita de seguimiento final. La población del estudio comprenderá pacientes adultos con asma en tratamiento de mantenimiento con corticosteroides inhalados (ICS) a dosis media o alta y un segundo medicamento controlador (por ejemplo, agonista β2 de acción prolongada), con antecedentes documentados de al menos dos exacerbaciones graves en los últimos 24 meses, de las cuales al menos una haya ocurrido en los últimos 12 meses, y donde el paciente sospeche que dichas exacerbaciones fueron desencadenadas por una infección de las vías respiratorias superiores (es decir, relacionadas con síntomas de resfriado común o gripe).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 99 YearsSexo: ALL

Criterios de inclusión

For inclusion in the study patients should fulfil the following criteria:
Provision of signed and dated written informed consent prior to any study specific procedures
Male or female aged 18 and above at the time of enrolment
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 CSP Appendix G), and a second controller medication as recommended in the GINA guidelines (ie, LABA, leukotriene receptor antagonist or sustained release theophylline). 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 oral corticosteroids (OCS), theophylline, tiotropium, or leukotriene receptor antagonists. The maintenance treatment must have been kept at the same or at a higher level these last 12 months.
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) or proof of positive response to mannitol challenge (a decrease in FEV1 by 15% \[PD15\] at ≤635 mg) (Anderson et al 2009) documented within 5 years prior to Visit 1. If historical documentation is not available, reversibility or proof of a positive response to a methacholine, histamine or mannitol challenge must be demonstrated and documented at Visit 1
Must answer "Yes" to the question "Does a cold or flu make your asthma worse?"
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 common 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 common cold or flu
Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception.
Negative pregnancy test (urine) for female patients of childbearing potential
Motivation (in the Investigator's opinion) to complete all study visits, the ability to communicate well with the Investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits
Ability to read and write and use the electronic devices, including demonstrating an acceptable technique when using the ePRO device, home spirometer and the I-neb

Criterios de exclusión

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)
Previous randomization to treatment in the present study
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
Lung disease other than asthma (eg, chronic obstructive pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis, active tuberculosis). Patients with CT or chest X-ray findings indicating bronchiectasis which in the opinion of the Investigator are not clinically significant may be enrolled at the discretion of the Investigator
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
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, or 5 times the half-life (whichever is the longest) of the biologic or small molecule IMP
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
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 ≥150 mmHg
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
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
Prolonged QTcF \>450 ms (for both gender) or shortened QTcF \<340 ms or family history of long QT syndrome
PR(PQ) interval shortening \<120ms (PR\<120 ms but \>110 ms is acceptable if there is no evidence of ventricular pre-excitation).
PR(PQ) interval prolongation (\>240ms), intermittent second or third degree AV block, or AV dissociation
QRS duration \>120ms including persistent or intermittent bundle branch block
Patients with implantable cardiac defibrillator (ICD) or a permanent pacemaker and patients with symptomatic ventricular and / or atrial tachyarrhythmias
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
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
History of hypersensitivity to natural or recombinant Interferon beta-1a or to any of the drug preparation excipients
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
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
History of epilepsy or seizures after the age of 5 years, other than febrile childhood seizure(s)
History of drug or alcohol abuse within 12 months prior to enrolment
Patients who have hepatic serum enzyme levels ≥2.5 times the normal range
Positive test for serum hepatitis B surface antigen, hepatitis C antibody, or HIV
Patients with a smoking history of ≥20 pack-years (1 pack year = 20 cigarettes smoked per day for one year)
Female who is breast-feeding, pregnant (verified by urine dipstick pregnancy test) or intends to become pregnant during the study
Patients who are unable to demonstrate an acceptable spirometry technique
Patients that have previously been included in studies evaluating the investigational medicinal product

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Interferon beta-1a Nebuliser solution 48 μg/mL

Placebo

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores