Clinical study to evaluate the the efficacy and safety of two doses of nebulised budesonide delivered by the VR475 Inhalation System, in comparison to conventionally nebulised budesonide, in patients with uncontrolled asthma

Phase 1

• Conditions: ncontrolled Asthma; MedDRA version: 19.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

• Registration Number: EUCTR2015-000353-20-HU
• Lead Sponsor: Vectura Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-13
• Last Update Posted: 6 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1.Adolescents aged 12 to 17 years (inclusive) and adults aged 18 to 74 years (inclusive). For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are = 18 years of age;
2.FEV1 reversibility (increase of at least 12% in absolute FEV1 and 200 ml from pre-bronchodilator value within 15-30 minutes after the use of inhaled bronchodilator) at the Screening or Randomisation Visits or during past 24 months;
A positive airways hyper-responsiveness test (fall in FEV1 from baseline of = 20% with standard doses of methacholine or histamine, or =15% with standardised hyperventilation, hypertonic saline or mannitol
challenge) during the past 24 months is also acceptable;
3. High dose inhaled glucocorticosteroid at a total daily dose of = 500 µg of fluticasone proprionate DPI or equivalent) for at least 3 months prior to the Screening Visit;
4. Treatment with at least a second asthma controller medication (i.e. not a short acting ß-agonist [SABA]) for at least 3 months prior to the Screening Visit;
5. FEV1 <80% of predicted value at the Screening and Randomisation Visits;
6. ACQ-5 score (symptom-only version) of 1.5 or higher at the Screening and Randomisation Visits;
7. Subjects with a previously confirmed history of at least two clinically significant asthma exacerbations defined as those requiring treatment or increased treatment with oral/systemic corticosteroids for at least 3 days and/or requiring hospitalisation and/or visit to an emergency department for an exacerbation in the 12 months prior to the Screening Visit, despite the use of high-dose ICS and at least one additional controller medication (or Symbicort SMART) at the time the exacerbation occurred;
8. Written informed consent obtained from the subject or subject’s parents/legal representatives (according to local regulations) and written or verbal assent by the subject (when appropriate), prior to participation in the study;
9. A negative pregnancy test must be available for any women of childbearing potential at the Screening and Randomisation Visits (prior to randomisation to one of the treatment groups);
10. Subjects able to read, comprehend and write at a level sufficient to complete study-related materials.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 490
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Asthma exacerbation or significant change in asthma treatment within the 4 weeks prior to the Screening Visit or during the Screening Period;
2. Abnormal lab values for biochemistry tests during the Screening Period that may indicate impaired ability to metabolise and/or excrete budesonide (aspartate transaminase [AST], alanine transaminase [ALT] > 3 times upper limit of normal range, serum creatinine > 1.5 times upper limit of normal range).
3.Current smokers or subjects with a recent smoking history (less than 6 months before randomisation) of =10 pack years (number of pack years = number of cigarettes per day / 20 x number of years smoked);
4.Presence of a clinically important lung condition other than asthma. This includes, but is not limited to, current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer;
5.Subjects with a diagnosis of active malignancy or in the process of investigation for a suspected malignancy. Subjects with a past medical history of malignancy can be allowed in the trial if in remission and provided anyone with a diagnosis of a recurrent malignant tumour or having received treatment for a malignancy within 12 months prior to the Screening Visit are excluded;
6.Subjects with a known immunodeficiency (e.g. human immunodeficiency virus),) or receiving immunosuppressant and/or immune modulating therapy (e.g. rheumatoid arthritis) other than that explained by the use of corticosteroids taken as therapy for asthma;
7. Subjects who have clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that were uncontrolled with standard treatment and which in the investigator’s opinion places the subject at undue risk by participating in the study;
8. History of substance abuse that may impair or risk the subject’s full participation in the study, in the judgment of the investigator;
9. Treatment with other investigational treatment within 4 weeks prior to the Screening Visit;
10. Regular oral/systemic corticosteroids for the treatment of conditions other than asthma in the 3 months prior to the Screening Visit;
11. History of allergy or adverse experience with budesonide or any of the excipients of budesonide nebuliser suspension (see VR475 Investigator’s Brochure 2016);
12. Use of a monoclonal antibody for the treatment of asthma within the 6 months prior to the Screening Visit;
13.Pregnant or lactating females. or females who are planning to become pregnant during the study.
14. Subjects with features suggestive of Cushing's syndrome;
15. Subjects who have failed screening twice before in this study or who have completed this study;
16. Treatment with the following medications during the Screening Period: benzodiazepines, barbiturates and opiates (except at prescription doses for analgesia and/or insomnia), new or nonmaintenance
immunotherapy, methotrexate, oral gold, dapsone or i.v. ? globulin, monoclonal antibodies, anti-IgE treatment, ß-blockers, macrolides (either as a chronic therapy or as an antimicrobial treatment for infection) and any investigational treatment other than the study medication.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified