Asthma not adequately controlled with inhaled corticosteroids and long acting beta-agonists MedDRA version: 17.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Secukinumab
Product Code: AIN457
Pharmaceutical Form: Powder for solution for injection/infusion
Current Sponsor code: AIN457
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Male and female adult patients aged = 18 - 75 years with asthma >1 year duration diagnosed according to the GINA guidelines (GINA 2010). 3. Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 39 kg/m2. See Appendix 3 of this protocol for BMI ranges. 4. Daily treatment with > 1000µg beclomethasone dipropionate (BDP), or equivalent, plus a LABA (GINA step 4/5 therapy) for = 3 months prior to Day 1, that has been stable for at least 4 weeks prior to screening. (Subjects may be enrolled on > 1000µg beclomethasone dipropionate (BDP) in the absence of a LABA if they have had an adverse reaction or worsening of asthma attributed to LABA therapy or if, in the opinion of the investigator, they are at high risk of adverse events to LABA therapy, or if the patient avoids LABA therapy due to concerns about such events). 5. Asthma which is not adequately controlled on current treatment, as demonstrated by an Asthma Control Questionnaire (ACQ) score of = 1.5 at screening and baseline (see Appendix 4). 6. Peripheral blood eosinophil count =65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, who are unwilling to use effective contraception during the study and for 16 weeks after stopping treatment. 2. Use of other investigational drugs at the time of screening, or within 30 days or 5 half-lives of screening, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations. 3. Treatment with the following medications is not permitted: Betablockers within 5 half lives prior to Run-in visit; Omalizumab or other monoclonal antibody treatment within 4 months prior to Run-in ; Methotrexate, gold salts, cyclosporin, troleandomycin within 3 months prior to Run-in; and other general immune suppressants within 4 months prior to Run-in. Oral steroids up to 20 mg prednisolone daily or equivalent are permitted if stable for at least 4 weeks prior to randomization (Day 1). 4. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 5. The presence of any clinically relevant ECG abnormalities. 6. Diagnosed with COPD as defined by the GOLD guidelines (Global Initiative for Chronic Obstructive Lung Disease 2008). 7. A history of allergic bronchopulmonary aspergillosis. 8. Patients who have had an asthma attack/exacerbation requiring a change in maintenance ICS or OCS treatment, or a short burst of systemic corticosteroids, within 4 weeks prior to screening. 9. Patients who have had a respiratory tract infection within 4 weeks prior to screening. 10. History of certain malignancies within the past 5 years 11. Pregnant or nursing women. 12. Smokers or those who have a smoking history of greater than 10 pack years 13. Donation or loss of 400 ml or more of blood within eight weeks prior to first dose 14. Significant illness within two (2) weeks prior to first dose. 15. Recent and/or recurrent history of autonomic dysfunction 16. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests 17. History of recurrent staphylococcal of fungal infections 18. Any live vaccines before screening, during the study, and after the last dose of secukinumab starting from 6 weeks before screening, during the study, and after the last dose 19. Maintenance Immunotherapy for allergies allowed if maintenance dose has been administered for at least 3 months prior to Run-in visit, and is expected to remain unchanged throughout the course of the study. 20. History of immunodeficiency diseases, including a positive HIV test result. 21. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 22. drug or alcohol abuse within the 12 months prior to dosing 23. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis. 24. No person directly associated with the administration of the study is allowed to participate as a study subject. No family member of the investigational study staff is
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether treatment with 10 mg/kg secukinumab versus placebo over 8 weeks, in individuals with asthma who are symptomatic despite treatment with high doses of ICS, leads to significant improvement in the severity of asthma as measured by change in the asthma control questionnaire (ACQ) score at Day 85.; Secondary Objective: To assess whether treatment with 10 mg/kg secukinumab versus placebo over 8 weeks, in individuals with asthma who are symptomatic despite treatment with high doses of ICS, leads to improvement in the forced expiratory volume in one second (FEV1) at Day 85. • To assess whether treatment with 10 mg/kg secukinumab versus placebo over 8 weeks, in individuals with asthma who are symptomatic despite treatment with high doses of ICS, leads to improvement in: - Symptoms of asthma and lung function monitored using an electronic device - Asthma Quality of Life Questionnaire (AQLQ) Indirect measures of airway inflammation, as measured by: - Reduction in exhaled nitric oxide - Reduction in sputum neutrophils • To assess the safety and tolerability of secukinumab in patients with bronchial asthma • To assess the pharmacokinetics of secukinumab in patients with bronchial asthma ; Primary end point(s): The primary efficacy endpoint is the change in ACQ score (?ACQ) from baseline to Day 85. The ACQ score ranges from 0 to 6 with lower scores reflecting better asthma control. Without loss of generality, ?ACQ is defined as baseline minus Day 85 so that improvements in asthma control translate to positive change scores. The primary analysis will consist of an unstructured mean and variance mixed effects regression model for the repeated measures on ?ACQ. The outcome will be the change in ACQ from baseline to each of Days 29, 57 and 85 and in | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: day 0 through day 197 (end of study); Secondary end point(s): Efficacy / Pharmacodynamics - Forced expiratory volume in one second (FEV1) prior to bronchodilation - FEV1 following bronchodilation - MMEF before and after bronchodilation - FeNO - AQLQ - Sputum neutrophils at Day 85 - Graphical summaries of daily symptoms of asthma and lung function measured at home will be displayed, and additional exploratory analyses on these endpoints will be performed as appropriate. Safety - Vital signs - ECG evaluations - Standard clinical laboratory evaluations - Special clinical laboratory evaluations - Adverse events - concomitant medications/significant non-drug-therapies Health related quality of life Pharmacokinetics Pharmacogenetics RNA expression profiling Other biomarkers PK/PD | — |
Countries
Belgium, Bulgaria, Germany, Romania, United Kingdom, United States
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed