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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02491684




Registration number
NCT02491684
Ethics application status
Date submitted
16/06/2015
Date registered
8/07/2015
Date last updated
12/02/2019

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
D6230C00001
Universal Trial Number (UTN)
Trial acronym
INEXAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Interferon beta-1a Nebuliser solution 48 µg/mL
Treatment: Drugs - Placebo

Placebo Comparator: Placebo (matching) - Placebo, once daily inhalation for 14 days

Experimental: Interferon beta-1a - Interferon beta-1a, 24 µg (metered dose) once daily inhalation for 14 days


Treatment: Drugs: Interferon beta-1a Nebuliser solution 48 µg/mL
Interferon beta-1a, 0,5 ml (24 µg, metered dose) once daily inhalation for 14 days

Treatment: Drugs: Placebo
Placebo solution for once daily inhalation for 14 days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment - 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
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
an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or
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.
Timepoint [1] 0 0
Day 1 - 14 of the treatment phase.
Secondary outcome [1] 0 0
Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation - Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations within 7 and 30 days after the start of treatment (Day 1).
A severe exacerbation was defined as worsening 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 3 consecutive days and/or
an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or
an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids.
The numbers of patients with severe asthma exacerbations with onset during Days 1 - 7 and Days 1 - 30 are presented for each treatment group.
Timepoint [1] 0 0
Day 1 of treatment phase up to 30 days post-randomisation.
Secondary outcome [2] 0 0
Proportion of Patients With Moderate Asthma Exacerbation Within 7, 14 and 30 Days Following Randomisation - Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing moderate exacerbations within 7, 14 and 30 days after the start of treatment (Day 1).
A moderate exacerbation was defined as a temporary increase in maintenance therapy in order to prevent a severe event supported by a sustained (2 or more days) worsening in at least one key control metric, including asthma score, rescue use, night time awakening or morning peak expiratory flow.
The numbers of patients with moderate exacerbations with onset during Days 1 - 7, Days 1 - 14 and Days 1 - 30 are presented for each treatment group.
With respect to the Day 1-7 analysis, the model did not converge so the analysis could not be performed.
Timepoint [2] 0 0
Day 1 of treatment phase up to 30 days post-randomisation.
Secondary outcome [3] 0 0
Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation - The time to first event was calculated as start date of events - date of randomisation + 1.
Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed.
The median time to first exacerbation was not calculated in either treatment group due to low numbers of events.
Timepoint [3] 0 0
From Day 1 of treatment phase up to 30 days post-randomisation.
Secondary outcome [4] 0 0
Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation - The time to first event was calculated as start date of events - date of randomisation + 1.
Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed.
The median time to first exacerbation was not calculated in either treatment group due to low numbers of events.
Timepoint [4] 0 0
From Day 1 of treatment phase up to 30 days post-randomisation.
Secondary outcome [5] 0 0
Duration of Moderate or Severe Exacerbations - The duration of each individual moderate or severe exacerbation was calculated as:
Cessation date of exacerbation - Start date of exacerbation + 1.
The start date of a severe exacerbation was defined as the start date of systemic corticosteroids or increase of systemic corticosteroids or emergency room visit or hospital admission, whichever occurred first. The stop date was defined as the last day of systemic corticosteroids/increase of systemic corticosteroids or hospital discharge, whichever occurred last.
The start date of a moderate exacerbation was defined as the first day of increase in temporary maintenance therapy. The stop date was defined as the last day of this treatment.
The mean duration of moderate or severe exacerbations is presented for each treatment group.
Timepoint [5] 0 0
Day 1 of treatment phase up to 30 days post-randomisation.
Secondary outcome [6] 0 0
Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6) - The ACQ-6 consists of 6 questions to assess asthma control, each question measured on a 7-point scale scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 total score is computed as the un-weighted mean of the responses to the 6 questions. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The change from baseline at Visit 4 (Day 7 +/- 1), at Visit 6 (Day 14 +/- 1) and at Visit 8 (Day 30) is presented for the total score and for each of the 6 questions.
Timepoint [6] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [7] 0 0
AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days - Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary on a daily basis. Symptoms were recorded using a scale of 0 to 3 where 0 indicates no asthma symptoms up to an absolute score of 3. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The total daily asthma symptom score was calculated by taking the sum of the night-time and daytime asthma scores recorded each day. The outcome variable is the area under the curve (AUC) for change from baseline in day-time, night-time and total daily asthma symptom scores over Days 1-14, Days 1-7, Days 8-14 and Days 15-30.
Timepoint [7] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [8] 0 0
Change in the Proportion of Night-time Awakening Using the ePRO Questionnaire From Baseline up to 30 Days - Night-time awakenings due to asthma symptoms were recorded by the patient in the Asthma Daily Diary each morning by answering the question whether he/she woke up during the night due to asthma symptoms with a 'yes' or 'no' response.
Biweekly means were calculated as the percentages of times the subject answered 'yes' over a period of 14 sequential days. Biweekly means are presented for the periods over Days 2-15 and Days 16-30.
Timepoint [8] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [9] 0 0
Change in Health-related Quality of Life as Measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) From Baseline up to 30 Days - The AQLQ(S) was used to assess health-related quality of life and consisted of 32 questions. Patients were asked to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The questions were allocated to 4 domains assessing:
activity limitation,
symptoms,
emotional function, and
environmental stimuli
The overall score was calculated as the mean of the responses to all questions. The mean change in overall score from baseline at Visit 6 (Day 14+/-1) and Visit 8 (Day 30) are presented.
Timepoint [9] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [10] 0 0
AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days - Patients recorded the number of reliever medication inhalations taken twice daily in the Asthma Daily Diary. The number of inhalations taken between the morning and evening lung function assessments were recorded in the evening. The number of inhalations taken between the evening and morning lung function assessments were recorded in the morning. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The AUC for change from baseline over Days 1-14 (inclusive of Days 1 and 14) is presented.
Timepoint [10] 0 0
From baseline up to Day 14 of treatment phase.
Secondary outcome [11] 0 0
AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days - Patients measured morning PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Timepoint [11] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [12] 0 0
AUC for Change in the Morning Forced Expiratory Volume in 1 Second (FEV1) From Baseline up to 30 Days - Patients measured morning FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Timepoint [12] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [13] 0 0
AUC for Change in the Evening PEF From Baseline to up to 30 Days - Patients measured evening PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Timepoint [13] 0 0
From baseline up to 30 days after start of treatment phase.
Secondary outcome [14] 0 0
AUC for Change in the Evening FEV1 From Baseline up to 30 Days - Patients measured evening FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation.
The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30.
Timepoint [14] 0 0
From baseline up to 30 days after start of treatment phase.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Bedford Park
Recruitment hospital [2] 0 0
Research Site - New Lambton
Recruitment hospital [3] 0 0
Research Site - Westmead
Recruitment hospital [4] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
2310 - New Lambton
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Caba
Country [3] 0 0
Argentina
State/province [3] 0 0
Ciudad Autonomade Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Nueve de julio
Country [5] 0 0
Argentina
State/province [5] 0 0
Quilmes
Country [6] 0 0
Colombia
State/province [6] 0 0
Bogota
Country [7] 0 0
Colombia
State/province [7] 0 0
Bogotá
Country [8] 0 0
Colombia
State/province [8] 0 0
Floridablanca
Country [9] 0 0
France
State/province [9] 0 0
Dijon
Country [10] 0 0
France
State/province [10] 0 0
Lyon Cedex 04
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Montpellier Cedex 5
Country [13] 0 0
France
State/province [13] 0 0
Paris Cedex 18
Country [14] 0 0
France
State/province [14] 0 0
Pessac
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Bucheon-si
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Jeonju-si
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Marbella (Málaga)
Country [20] 0 0
Spain
State/province [20] 0 0
Málaga
Country [21] 0 0
Spain
State/province [21] 0 0
Sevilla
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Blackpool
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Bradford
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Lancaster
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Leeds
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Manchester
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Nottingham
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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
Trial website
https://clinicaltrials.gov/show/NCT02491684
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Per Gustafson, MD PhD
Address 0 0
AstraZeneca, R&D mölndal
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications