A Study of Lebrikizumab in Patients Whose Asthma is Uncontrolled With Inhaled Corticosteroids and A Second Controller Medication (LUTE)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will assess the efficacy and safety of lebrikizumab in patients with asthma whose disease remains uncontrolled despite daily therapy with an inhaled corticosteroid and a second controller medication. Patients will be randomized in a 1:1:1:1 ratio to receive double-blind treatment with subcutaneous lebrikizumab ("highest", "middle", "lowest" dose) or placebo every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This will be followed by a 52-week double-blind active treatment extension. The anticipated time on study treatment is up to 104 weeks. There will be a safety follow-up of 24 weeks after the last dose of study drug for all patients.

Inclusion Criteria:

• Adult patients, 18 to 75 years of age at Visit 1
• Asthma diagnosis for >/= 12 months prior to the start of screening (Visit 1)
• Bronchodilator response during screening
• Pre-bronchodilator FEV1 40%-80% of predicted during screening
• On ICS (inhaled corticosteroids) 500-2000 mcg/day of fluticasone propionate DPI or equivalent for >/= 6 months prior to the start of screening (Visit 1) with no anticipated changes throughout the study
• On an eligible second controller medication (LABA, LAMA, LTRA or theophylline within the prescribed dosing range)
• Uncontrolled asthma as defined by protocol both during screening period and at time of randomization
• Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during screening period confirming the absence of other lung disease
• Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

• History of severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
• Use of zileuton or roflumilast within 6 months prior to screening
• Maintenance oral corticosteroid therapy, defined as daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to Visit 1
• Treatment with systemic (oral, intravenous or intramuscular) corticosteroids within the 4 weeks prior to Visit 1
• Major episode of infection within 4 weeks prior to Visit 1 or treatment with oral antibiotics within 2 weeks prior to Visit 1
• Active parasitic infection within the 6 months prior to Visit 1
• Active tuberculosis requiring treatment within the 12 months prior to Visit 1
• Known immunodeficiency, including, but not limited to, HIV infection
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma
• Known malignancy or current evaluation for a potential malignancy
• Current smoker or former smoker with a history >10 pack years
• History of alcohol, drug or chemical abuse
• Initiation or change in allergen immunotherapy within 3 months prior to Visit 1
• Use of biologic therapy including omalizumab during 6 months prior to Visit 1
• Receipt of live/attenuated vaccine within 4 weeks prior to Visit 1
• Pregnant or lactating women
• Body mass index (BMI) > 38 kg/m2
• Body weight < 40 kg