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 - INEXAS

Study identifier:D6230C00001

ClinicalTrials.gov identifier:NCT02491684

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

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

Medical condition

asthma

Phase

Phase 2

Healthy volunteers

Study drug

Interferon beta-1a Nebuliser solution 48 μg/mL, Placebo

Sex

All

Actual Enrollment

121

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 21 Jul 2015

Primary Completion Date: 24 Nov 2016

Study Completion Date: 24 Nov 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Prevention

Verification:

Verified 01 Jan 2019 by AstraZeneca

Collaborators

Inclusion and exclusion 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

No locations available

Arms	Assigned Interventions
Placebo Comparator: Placebo (matching) Placebo, once daily inhalation for 14 days	Drug: Placebo Placebo solution for once daily inhalation for 14 days
Experimental: Interferon beta-1a Interferon beta-1a, 24 μg (metered dose) once daily inhalation for 14 days	Drug: Interferon beta-1a Nebuliser solution 48 μg/mL Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Per Gustafson

AstraZeneca, R&D mölndal