A Study of Lebrikizumab in Participants With Uncontrolled Asthma on Inhaled Corticosteroids and a Second Controller Medication

Study Overview
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Brief Summary
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This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of lebrikizumab in participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication. Participants will be randomized in 1:1:1 ratio to receive double-blind treatment with either lebrikizumab (high or low) or placebo, administered as subcutaneous (SC) injection 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. Participants who were assigned to placebo during the placebo-controlled period of the trial will be re-randomized at Week 52 to receive blinded SC lebrikizumab 37.5 milligrams (mg) or 125 mg every 4 weeks from Weeks 53 to 104. The anticipated time on study treatment is 104 weeks. After study treatment, all participants will complete a 20-week safety follow-up.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety 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: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthma diagnosis for greater than equal to (>/=) 12 months at Visit 1 Bronchodilator response at Visit 1, 2, or 3 Pre-bronchodilator FEV1 of 40 percent (%) - 80% predicted at both Visits 2 and 3 On ICS therapy at a total daily dose of 500-2000 microgram (mcg) of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/= 6 months prior to Visit 1 On an eligible second controller medication (long-acting Beta-agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist [LAMA], or theophylline) for 6 months prior to Visit 1 Uncontrolled asthma at Visit 1 and/or Visit 2, and at Visit 3 Chest X-ray or computed tomography (CT) scan within 3 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) confirming the absence of other clinically significant lung disease Demonstrated adherence with controller medication during the screening period Exclusion Criteria: History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection Maintenance oral corticosteroid therapy within 3 months of Visit 1 Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study Infection requiring hospital admission for >/=24 hours 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 Active tuberculosis requiring treatment within 12 months prior to Visit 1 Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection Evidence of acute or chronic hepatitis or known liver cirrhosis History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma Known current malignancy or current evaluation for potential malignancy Current smoker or former smoker with a history of greater than (>) 10 pack-years History of alcohol or drug abuse Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab; use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening

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 (125 mg)<br>Participants will receive SC injection of lebrikizumab (125 mg) every 4 weeks for 104 weeks. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.<br>* Other names: RO5490255;|
| Experimental: Lebrikizumab (37.5 mg)<br>Participants will receive SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.<br>* Other names: RO5490255;|
| Placebo Comparator: Placebo<br>Participants will receive SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at 125 or 37.5 mg for 52 weeks during active treatment extension period. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.<br>* Other names: RO5490255;Drug: Placebo<br>* Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 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 |  | Baseline up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) |  | Baseline, Week 52 | 
| Time to First Asthma Exacerbation |  | Baseline up to Week 52 | 
| Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score |  | Baseline, Week 52 | 
| Change from Baseline In Asthma Rescue Medication (Number of Puffs or Nebulized Treatments) |  | Baseline, Week 52 | 
| Rate of Urgent Asthma-Related Urgent Health Care Utilization |  | Baseline up to Week 52 | 
| Percentage of Participants With Adverse Events |  | Baseline up to Week 124 | 
| Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab |  | Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 64, 76, 92, 104, 112, and 124) | 
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score |  | Baseline, Week 52 | 
| Minimum Serum Concentration (Cmin) of Lebrikizumab |  | Predose (0 hour) on Weeks 4, 12, 24, 36, and 52 |