A Study in Asthma Patients to Evaluate Efficacy, Safety and Tolerability of 14 Days Once Daily Inhaled Interferon Beta-1a After the Onset of Symptoms of an Upper Respiratory Tract Infection
Condition: Asthma
MeSH terms: Infections; Respiratory Tract Infections; Asthma
Intervention: Interferon beta-1a Nebuliser solution 48 μg/mL; Placebo
Intervention description: Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days; Placebo solution for once daily inhalation for 14 days
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: asthma; Upper Respiratory Tract Infection; exacerbation; Interferon; efficacy; safety; prevention

Summary:

      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
    

Eligibility criteria:

        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 enrolment

          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 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.

          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) 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

          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 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

          7. Female patients must be 1 year post-menopausal, surgically sterile, or using an
             acceptable method of contraception.

          8. Negative pregnancy test (urine) for female patients of childbearing potential

          9. 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

         10. 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

        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, 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

          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, or 5 times the half-life (whichever is the longest) of the
             biologic or small molecule IMP

          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 ≥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

          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 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