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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment
研究概览
简要总结
A study to investigate if inhaled Interferon beta-1a is safe and tolerated, and can prevent or reduce the severity of asthma attacks when administered to asthma patients at the onset of symptoms of common cold or influenza
详细描述
The study will consist of a Pre-Treatment Phase followed by a Treatment Phase. Patients are screened and enter the Pre-Treatment phase where they remain until they develop symptoms of a common cold or the flu. During this Pre-Treatment Phase patients will be asked daily if they think they have a common cold or the flu. When the patient answers yes to the question that he/she is coming down with a common cold or the flu, arrangements are made to evaluate the patient at the study site and, if eligible, enters the Treatment Phase. Baseline assessments are performed and the patient is randomized 1:1 to receive 24 μg (metered dose) inhaled Interferon beta-1a or placebo once daily for 14 days (delivered by the I-neb® device [Philips Respironics]). Treatment should start as soon as possible but no later than 48 hours after the onset of the first of the common cold or flu symptoms. Patients will be assessed with regards to exacerbations and changes in respiratory symptoms and reliever medication use at home using an ePRO device. Lung function will be measured both at home by the patients and at the study site. There will be five clinical visits during the Treatment Phase and two visits after the end of treatment; efficacy and safety will be monitored until 2-3 weeks after end of treatment when a final follow-up visit will take place.
The study population will comprise adult asthmatic patients on a maintenance treatment of medium to high dose inhaled corticosteroids and a second controller medication (eg, long- acting β2 agonist), with a documented history of at least two severe exacerbations within the last 24 months, of which at least one has occurred during the last 12 months, and it is suspected by the patient that these aforementioned exacerbations were triggered by an upper respiratory tract infection (ie, related to symptoms of a common cold or the flu).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •Patients should not enter the study if any of the following exclusion criteria are fulfilled:
- •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
研究组 & 干预措施
Placebo (matching)
Placebo, once daily inhalation for 14 days
干预措施: Placebo (Drug)
Interferon beta-1a
Interferon beta-1a, 24 μg (metered dose) once daily inhalation for 14 days
干预措施: Interferon beta-1a Nebuliser solution 48 μg/mL (Drug)
结局指标
主要结局
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment
时间窗: Day 1 - 14 of the treatment phase.
Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations during the 14 day treatment phase following the onset of an URTI in asthmatic patients. A severe exacerbation was defined as worsening asthma symptoms and 1. use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or 2. an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or 3. an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The number of patients with severe asthma exacerbations with onset during the treatment phase is presented for each treatment group.
次要结局
- Duration of Moderate or Severe Exacerbations(Day 1 of treatment phase up to 30 days post-randomisation.)
- AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days(From baseline up to Day 14 of treatment phase.)
- Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation(Day 1 of treatment phase up to 30 days post-randomisation.)
- Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation(Day 1 of treatment phase up to 30 days post-randomisation.)
- Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation(From Day 1 of treatment phase up to 30 days post-randomisation.)
- Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation(From Day 1 of treatment phase up to 30 days post-randomisation.)
- AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- AUC for Change in the Evening PEF From Baseline to up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6)(From baseline up to 30 days after start of treatment phase.)
- AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days(From baseline up to 30 days after start of treatment phase.)
- AUC for Change in the Evening FEV1 From Baseline up to 30 Days(From baseline up to 30 days after start of treatment phase.)