Uncontrolled Asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Budesonide nebuliser suspension delivered via the VR475 Inhalation System
Product Code: VR475
Pharmaceutical Form: Nebuliser suspension
IN
Sponsors
Vectura Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
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 non-maintenance immunotherapy, methotrexate, oral gold, dapsone or i.v. ? globulin, monoclonal antibodies, anti-IgE treatment, ß-blockers, macrolides (eit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical efficacy, safety and tolerability of VR475 1 mg/2 ml twice daily given for 52 weeks compared to placebo. ; Secondary Objective: -To evaluate the clinical efficacy, safety and tolerability of VR475 1 mg/2 ml compared to conventionally nebulised budesonide 1 mg/2 ml twice daily; -To investigate the dose-response relationship of VR475; -To evaluate any change from Baseline to End-of-Treatment in OCS dose in those subjects receiving OCS at Baseline. ;Primary end point(s): The annualised rate of clinically significant exacerbations during the Treatment Period.;Timepoint(s) of evaluation of this end point: During Treatment Period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in in-clinic pre-bronchodilator FEV1 from baseline during the Treatment Period; - Change in in-clinic forced expiratory flow between 25% and 75% of FVC [FEF25-75]) from baseline during the Treatment Period; - Time to first clinically significant exacerbation; - Change in ACQ-5 scores from baseline during the Treatment Period. - Proportion of subjects without a clinically significant exacerbation; - Annualised exacerbation rate (all exacerbations); - Time to first exacerbation (all exacerbations); - Proportion of subjects without an exacerbation (all exacerbations); - Change in OCS dose from baseline to End-of-Treatment/Week 52, in subgroup of OCS users at baseline; - Proportion of OCS users with 50% or 100% OCS dose reductions from baseline to End-of-Treatment/Week 52; - Total OCS dosage; - Total OCS/systemic corticosteroid dosage given for exacerbations; - Change in in-clinic pulmonary function test (PFT) assessments ( FEV1 % predicted, forced vital capacity [FVC]) from baseline during the Treatment Period; - Change in am and pm PEF from baseline during the Treatment Period; - Change in reliever medication use from baseline during the Treatment Period; - Change in symptom-free days from baseline during the Treatment Period; - Change in reliever-medication-free days from baseline during the Treatment Period; - Change in uncontrolled asthma days from baseline during the Treatment Period; - Change in night-time awakenings due to asthma from baseline during the Treatment Period; - Change in scores from EQ-5D questionnaire from baseline during the Treatment Period; - Change in AQLQ +12 s | — |
Countries
Bulgaria, Germany, Greece, Hungary, Philippines, Poland, Romania, Serbia, Ukraine, United Kingdom
Contacts
Public ContactClinical Trials Information
Vectura Limited
Outcome results
None listed