Asthma Severe corticosteroid dependent Asthma
Conditions
Interventions
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Patients, age 18-75 years at the time of informed consent - Severe asthma despite intensive follow-up by an asthma specialist for at least 6 months prior to Visit 1 - Baseline forced expiratory volume in 1 second (FEV1) * 40% of predicted prior to randomization -Receiving high doses of inhaled glucocorticosteroids at a total daily dose of * 1500 mcg beclomethasone dipropionate daily or equivalent and long-acting beta-adrenoceptor agonist (LABA), with or without an additional controller, for at least 3 months prior to Visit 1; - Chronic treatment with maintenance oral corticosteroids (prednisone/prednisolone) for at least 6 months prior to Visit 1 - Assessment to ensure diagnosis of refractory asthma and oral corticosteroid dependence on minimal effective or maximum tolerated dose prior to visit 1 with compliance
Exclusion criteria
Exclusion criteria: - History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection - Asthma exacerbation within 28 days prior to Visit 1 or during screening (prior to Visit 3 - For adults: Active tuberculosis requiring treatment within the 12 months prior to visit 1 - Evidence of acute or chronic hepatitis or known liver cirrhosis - Known current malignancy or current evaluation for a potential malignancy - History of interstitial lung disease, chronic obstructive pulmonary disease, or other clinically significant lung disease other than asthma - Infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to visit 1 or during screening - Upper or lower respiratory tract infection within 4 weeks prior to visit 1 or during screening - Active parasitic infection or Listeria monocytogenes infection within 6 months prior to visit 1 or during screening - Current smoker or former smoker with a smoking history of >15 pack-years - Current use of an immunomodulatory/immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to visit 1 - Use of a licensed or investigational monoclonal antibody other than anti IL-13 or anti IL-4/IL-13, including, but not limited to, omalizumab, anti IL-5, or anti IL-17, within 6 months or 5 drug half-lives (whichever is longer) prior to visit 1 - Receipt of a live, attenuated vaccine within the 4 weeks prior to visit 1, during screening or anticipation of receipt of alive, attenuated vaccine throughout the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy Outcome Measures The primary efficacy outcome measure for this study is the following: * Relative change in daily OCS dose from baseline to Week 44 | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy Outcome Measures The secondary efficacy outcome measures include the following: * Absolute change in daily OCS dose from baseline to Week 44 * Percentage of patients achieving at least a 50% reduction in their daily OCS dose relative to baseline at Week 44 * Percentage of patients discontinuing OCS therapy or having achieved an adrenal maintenance dose up to Week 44 * Relative change in average OCS dose from Week 12 to Week 44 during the OCS reduction phase * Rate of asthma exacerbations during the 44-week DBPC period Safety Outcome Measures The safety outcome measures for this study are as follows: * Frequency and severity of treatment-emergent adverse events during the double-blind, placebo-controlled, active-treatment extension, long-term active-treatment extension, and safety follow-up periods * Incidence of anti-therapeutic antibodies (ATAs) against lebrikizumab throughout the study Pharmacodynamic Outcome Measures The exploratory PD outcome measures for this study are as follows: * Change from baseline in serum periostin, FeNO, eosinophils, IgE, CCL-13, and CCL-17 * Exploratory PK/PD relationships Pharmacokinetic Outcome Measure The PK outcome measure for this study is as follows: * Predose serum lebrikizumab concentration (minimum concentration [Cmin]) at Weeks 4 (Cmin, wk4), 12 (Cmin, wk12), 24 (Cmin, wk24), 36 (Cmin, wk36), and 44 (Cmin, wk44) Exploratory Outcome Measures The exploratory outcome measures during the 44-week DBPC period include the following: * Relative change in daily OCS dose from baseline to Week 44, excluding OCS received during asthma exacerbation * Relative change in daily OCS dose at Week 44 using projected next OCS dose * Area under the curve (AUC) of OCS dose from Week 12 to Week 44 * Rate of asthma exacerbations during the 32-week OCS-reduction phase * Rate of urgent asthma-related healthcare utilization (i.e., hospitalizations, emergency department visits, and acute care visits) during | — |
Countries
Australia, Belgium, Canada, Chile, Czechia, Denmark, France, Germany, Mexico, Netherlands, New Zealand, Poland, Puerto Rico, Slovakia, Slovenia, Spain, Sweden, United Kingdom, United States of America
Outcome results
None listed