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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: lebrikizumab
* Drug: lebrikizumab
* Drug: lebrikizumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lebrikizumab - highest dose<br> | Drug: lebrikizumab<br>* subcutaneous dose every 4 weeks<br>|
| Experimental: lebrikizumab - lowest dose<br> | Drug: lebrikizumab<br>* subcutaneous dose every 4 weeks<br>|
| Experimental: lebrikizumab - middle dose<br> | Drug: lebrikizumab<br>* subcutaneous dose every 4 weeks<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* subcutaneous dose every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of asthma exacerbations during the 52-week placebo-controlled period |  | weeks 0-52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung function: pre-bronchodilator FEV1 |  | from baseline to week 52 | 
| Time to first asthma exacerbation |  | from baseline to week 52 | 
| Change in fractional exhaled nitric oxide (FeNO) |  | from baseline to week 52 | 
| Change in asthma-specific health-related quality of life, assessed by the Standardized Asthma Quality of Life Questionnaire (AQLQ[S]) |  | from baseline to week 52 | 
| Change in asthma rescue medication use |  | from baseline to week 52 | 
| Rate of urgent asthma-related health care utilization during the 52-week placebo-controlled period |  | from baseline to week 52 |