AsthmaPhase 2INEXASNCT02491684
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
A Phase 2 study testing Interferon beta-1a Nebuliser solution 48 μg/mL in people with Asthma, run by AstraZeneca at 35 sites in 7 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Asthma
- What is being tested?
- Interferon beta-1a Nebuliser solution 48 μg/mL
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 121 participants
- Where
- 35 sitesin 7 countries
- Study dates
- 21 Jul 2015to 24 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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?"
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- 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
Who cannot join
- 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
Show all 32Show fewer
- 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
Trial locations and contacts
35 sites in 7 countries.
35 sites in 7 countries
United Kingdom7 sites
Research Site
Blackpool, FY4 3AD
Research Site
Bradford, BD9 6RJ
Research Site
Lancaster, LA1 4RP
Research Site
Leeds, LS9 7TF
Research Site
Manchester, M23 9QZ
Research Site
Nottingham, NG5 1PB
Research Site
Southampton, SO9 4XY
France6 sites
Research Site
Dijon, 21079
Research Site
Lyon, 69317
Research Site
Marseille, 13015
Research Site
Montpellier, 34295
Research Site
Paris, 75877
Research Site
Pessac, 33604
Argentina5 sites
Research Site
Buenos Aires, C1414AIF
Research Site
CABA, C1425BEN
Research Site
Ciudad Autonomade Buenos Aires, 1426
Research Site
Nueve de Julio, B6500EZL
Research Site
Quilmes, B1878FNR
South Korea5 sites
Research Site
Bucheon-si, 14584
Research Site
Jeonju, 54907
Research Site
Seoul, 02559
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Spain5 sites
Research Site
Barcelona, 08003
Research Site
Málaga, 29010
Research Site
Marbella (Málaga), 29603
Research Site
Seville, 41071
Research Site
Valencia, 46017
Australia4 sites
Research Site
Bedford Park, 5042
Research Site
New Lambton, 2310
Research Site
Westmead, 2145
Research Site
Woolloongabba, 4102
Colombia3 sites
Research Site
Bogotá, 110311
Research Site
Bogotá
Research Site
Floridablanca, 680006
About this study
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
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
Read the detailed description
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).
- Conditions
- Asthma
- Being tested
- Interferon beta-1a Nebuliser solution 48 μg/mL, Placebo
- Keywords
- asthma, Upper Respiratory Tract Infection, exacerbation, Interferon, efficacy, safety, prevention
- Medical subject headings
- Asthma, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon beta-1a Nebuliser solution 48 μg/mLDrug
Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days
PlaceboDrug
Placebo solution for once daily inhalation for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo (matching) | Placebo comparator | Placebo, once daily inhalation for 14 days Receives: Drug: Placebo |
| Interferon beta-1a | Experimental | Interferon beta-1a, 24 μg (metered dose) once daily inhalation for 14 days Receives: Drug: Interferon beta-1a Nebuliser solution 48 μg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 - 14 of the treatment phase.
Secondary outcomes (14)
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.
Measured: 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
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.
Measured: Day 1 of treatment phase up to 30 days post-randomisation.
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.
Measured: From Day 1 of treatment phase up to 30 days post-randomisation.
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.
Measured: From Day 1 of treatment phase up to 30 days post-randomisation.
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.
Measured: Day 1 of treatment phase up to 30 days post-randomisation.
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.
Measured: From baseline up to 30 days after start of treatment phase.
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.
Measured: 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
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.
Measured: From baseline up to 30 days after start 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
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.
Measured: From baseline up to 30 days after start of treatment phase.
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.
Measured: From baseline up to Day 14 of treatment phase.
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.
Measured: 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
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.
Measured: 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
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.
Measured: From baseline up to 30 days after start of treatment phase.
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.
Measured: From baseline up to 30 days after start of treatment phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study start21 Jul 2015
- Primary completion24 Nov 2016
- Study completion24 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Per Gustafson, MD PhD, Study director, AstraZeneca, R&D mölndal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491684
- Sponsor's protocol ID
- D6230C00001
- Acronym
- INEXAS
- Status last verified
- Jan 2019
- First submitted
- 16 Jun 2015
- Last updated
- 12 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
McCrae C, Olsson M, Gustafson P, Malmgren A, Aurell M, Fageras M, Da Silva CA, Cavallin A, Paraskos J, Karlsson K, Wingren C, Monk P, Marsden R, Harrison T. INEXAS: A Phase 2 Randomized Trial of On-demand Inhaled Interferon Beta-1a in Severe Asthmatics. Clin Exp Allergy. 2021 Feb;51(2):273-283. doi: 10.1111/cea.13765. Epub 2020 Nov 3.
PubMed 33091192
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02491684
- Acronym / sponsor ID
- INEXAS / D6230C00001
- Conditions
- Asthma
- Keywords
- asthma, Upper Respiratory Tract Infection, exacerbation, Interferon, efficacy, safety, prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2015 (actual)
- Primary completion
- 24 Nov 2016 (actual)
- Study completion
- 24 Nov 2016 (actual)
- First posted
- 8 Jul 2015 (estimated)
- Results
- Posted 15 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (matching) | Placebo comparator | Drug: PlaceboPlacebo, once daily inhalation for 14 days |
| Interferon beta-1a | Experimental | Drug: Interferon beta-1a Nebuliser solution 48 μg/mLInterferon beta-1a, 24 μg (metered dose) once daily inhalation for 14 days |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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?"
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon beta-1a Nebuliser solution 48 μg/mLInterferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days | Drug | Interferon beta-1a |
| PlaceboPlacebo solution for once daily inhalation for 14 days | Drug | Placebo (matching) |
Primary outcome
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment
Time frame: 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.
14 secondary outcomes
Proportion of Patients With Severe Asthma Exacerbations Within 7 and 30 Days Following Randomisation
Time frame: 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
Time frame: Day 1 of treatment phase up to 30 days post-randomisation.
Time to First Severe Asthma Exacerbation During 30 Days Following Randomisation
Time frame: From Day 1 of treatment phase up to 30 days post-randomisation.
Time to First Moderate Asthma Exacerbation During 30 Days Following Randomisation
Time frame: From Day 1 of treatment phase up to 30 days post-randomisation.
Duration of Moderate or Severe Exacerbations
Time frame: Day 1 of treatment phase up to 30 days post-randomisation.
Change in Asthma Control From Baseline up to 30 Days as Measured by the Asthma Control Questionnaire (ACQ-6)
Time frame: From baseline up to 30 days after start of treatment phase.
AUC for Change in Daytime and Night-time Asthma Symptom Score From Baseline up to 30 Days
Time frame: 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
Time frame: From baseline up to 30 days after start 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
Time frame: From baseline up to 30 days after start of treatment phase.
AUC for Change in Daytime and Night-time Reliever Medication Use From Baseline up to 14 Days
Time frame: From baseline up to Day 14 of treatment phase.
AUC for Change in the Morning Peak Expiratory Flow (PEF) From Baseline to up to 30 Days
Time frame: 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
Time frame: 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
Time frame: From baseline up to 30 days after start of treatment phase.
AUC for Change in the Evening FEV1 From Baseline up to 30 Days
Time frame: From baseline up to 30 days after start of treatment phase.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33091192McCrae C, Olsson M, Gustafson P, Malmgren A, Aurell M, Fageras M, Da Silva CA, Cavallin A, Paraskos J, Karlsson K, Wingren C, Monk P, Marsden R, Harrison T. INEXAS: A Phase 2 Randomized Trial of On-demand Inhaled Interferon Beta-1a in Severe Asthmatics. Clin Exp Allergy. 2021 Feb;51(2):273-283. doi: 10.1111/cea.13765. Epub 2020 Nov 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Gustafson, MD PhD study director
AstraZeneca, R&D mölndal
35 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interferon beta-1a Nebuliser solution 48 μg/mL in people with Asthma, run by AstraZeneca at 35 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United Kingdom, France, Argentina, South Korea, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients With a Severe Asthma Exacerbation During 14 Days of Treatment (time frame: Day 1 - 14 of the treatment phase.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02491684, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.