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

NCT02491684 | Completed Phase 2 Results

• 1 other identifier: D6230C00001
• Study Type: interventional
• Target: 121
• Locations: 7 countries
• Sites: 35

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

Conditions

Asthma

Keywords

asthma; Upper Respiratory Tract Infection; exacerbation; Interferon; efficacy; safety; prevention

Outcome Measures

Primary Outcomes (1)

• 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 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.

  Day 1 - 14 of the treatment phase.

Secondary Outcomes (14)

• 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.

• Duration of Moderate or Severe Exacerbations

  Day 1 of treatment phase up to 30 days post-randomisation.

Study Arms (2)

Placebo (matching)

PLACEBO COMPARATOR

Placebo, once daily inhalation for 14 days

Drug: Placebo

Interferon beta-1a

EXPERIMENTAL

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

Drug: Interferon beta-1a Nebuliser solution 48 μg/mL

Interventions

Interferon beta-1a Nebuliser solution 48 μg/mL DRUG

Interferon beta-1a, 0,5 ml (24 μg, metered dose) once daily inhalation for 14 days

Interferon beta-1a

Placebo DRUG

Placebo solution for once daily inhalation for 14 days

Placebo (matching)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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?"
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Buenos Aires, C1414AIF, Argentina

Location

Research Site

CABA, C1425BEN, Argentina

Location

Research Site

Ciudad Autonomade Buenos Aires, 1426, Argentina

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Research Site

Nueve de Julio, B6500EZL, Argentina

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Quilmes, B1878FNR, Argentina

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Bedford Park, 5042, Australia

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New Lambton, 2310, Australia

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Westmead, 2145, Australia

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Woolloongabba, 4102, Australia

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Bogotá, 110311, Colombia

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Bogotá, Colombia

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Floridablanca, 680006, Colombia

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Dijon, 21079, France

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Lyon, 69317, France

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Marseille, 13015, France

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Montpellier, 34295, France

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Paris, 75877, France

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Pessac, 33604, France

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Bucheon-si, 14584, South Korea

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Jeonju, 54907, South Korea

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Seoul, 02559, South Korea

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Seoul, 03080, South Korea

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Seoul, 05505, South Korea

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Barcelona, 08003, Spain

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Marbella (Málaga), 29603, Spain

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Málaga, 29010, Spain

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Seville, 41071, Spain

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Valencia, 46017, Spain

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Blackpool, FY4 3AD, United Kingdom

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Bradford, BD9 6RJ, United Kingdom

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Lancaster, LA1 4RP, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Manchester, M23 9QZ, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Research Site

Southampton, SO9 4XY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33091192 DERIVED

MeSH Terms

Conditions

Asthma; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Infections

Limitations and Caveats

The study was terminated early due to the lower than expected rate of severe exacerbations in the study as a whole, and due to the observed lack of differential effect at interim analysis.

Results Point of Contact

• Title: Medical Science Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Per Gustafson, MD PhD

  AstraZeneca, R&D mölndal

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: July 8, 2015
• Study Start: July 21, 2015
• Primary Completion: November 24, 2016
• Study Completion: November 24, 2016
• Last Updated: February 12, 2019
• Results First Posted: January 15, 2019

Record last verified: 2019-01

Locations

FR (6); ES (5); AR (5); CO (3); AU (4); KR (5); GB (7)