A Study to Evaluate Safety and Efficacy of Lebrikizumab in Participants With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Phase II, randomized, double-blind, placebo-controlled, parallel-group clinical trial of lebrikizumab in participants with COPD and a history of exacerbations who are treated with inhaled corticosteroid (ICS) and at least one long-acting bronchodilator inhaler medication. This study will be conducted to assess the safety, efficacy, and patient-reported outcome (PRO) measures.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Chronic Obstructive Pulmonary Disease and a History of Exacerbations

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Lebrikizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of COPD greater than or equal to (>/=) 12 months prior to Visit 1 Post-bronchodilator FEV1/FVC less than (<) 0.70 at Visit 1 or 2 Post bronchodilator FEV1 <80% predicted at Visit 1 or 2 Documented history of one or more acute COPD exacerbations requiring treatment with systemic corticosteroids and/or antibiotics or hospitalization within 12 months prior to Visit 1 Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking >/=10 pack-years (20 cigarettes/day for 10 years) On inhaled corticosteroids (ICS) therapy for >/=6 months prior to Visit 1 On an eligible bronchodilator medication for >/=6 months prior to Visit 1 Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray prior to Visit 2 that confirms absence of clinically significant lung disease besides COPD Demonstrated adherence with background COPD inhaler medication during screening period For female participants of childbearing age, use of single or combined contraceptive methods for the duration of the study Exclusion Criteria: History of severe allergic reaction or anaphylactic reaction to biologic agent or known hypersensitivity to lebrikizumab injection History of clinically significant pulmonary disease other than COPD Diagnosis of alpha-1-antitrypsin deficiency Lung volume reduction surgery or procedure within 12 months prior to Visit 1 Supplemental oxygen requirement >2 liters/minute (L/min) at rest or with exertion Current diagnosis of asthma Participants participating in, or scheduled for, an intensive COPD rehabilitation program Maintenance oral corticosteroid therapy Treatment with systemic corticosteroids within 4 weeks prior to Visit 1 or during screen period Unstable ischemic heart disease or other relevant cardiovascular disorders Use of an immunomodulatory or immunosuppressive therapy including monoclonal antibodies (includes anti-interleukin-13 (IL) or anti-IL-4/IL-13 therapy) Body weight <40 kg Any infection that resulted in hospital admission for >/= 24 hours and/or treatment with oral, intravenous (IV), or intramuscular (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 or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening Received a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening Active tuberculosis requiring treatment within 12 months prior to Visit 1 Human immunodeficiency virus (HIV) or other known immunodeficiency Hepatitis or known liver cirrhosis Aspartate Aminotransferase (AST), Alanine Aminotransferase (ATL), or total bilirubin elevation >/=2.0 x upper limit of normal (ULN) during screening Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests History of alcohol or drug abuse Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Biomarker-high<br>Lebrikizumab will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-high. | Drug: Lebrikizumab<br>* Lebrikizumab 125 milligrams (mg) will be administered subcutaneously once in every 4 weeks.<br>|
| Experimental: Lebrikizumab: Biomarker-low<br>Lebrikizumab will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-low. | Drug: Lebrikizumab<br>* Lebrikizumab 125 milligrams (mg) will be administered subcutaneously once in every 4 weeks.<br>|
| Placebo Comparator: Placebo: Biomarker-high<br>Matching placebo will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-high. | Drug: Placebo<br>* Matching placebo will be administered subcutaneously once in every 4 weeks.<br>|
| Placebo Comparator: Placebo: Biomarker-low<br>Matching placebo will be administered subcutaneously once in every 4 weeks up to 24 weeks to the participants considered as biomarker-low. | Drug: Placebo<br>* Matching placebo will be administered subcutaneously once in every 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Pre-bronchodilator Forced Expiratory Volume (FEV1) at Week 12 |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Moderate or Severe COPD Exacerbation |  | Baseline up to Week 24 | 
| Absolute Change From Baseline in Post-bronchodilator FEV1 at Week 24 |  | Baseline, Week 24 | 
| Absolute Change From Baseline in Pre-bronchodilator FEV1 at Week 24 |  | Baseline, Week 24 | 
| Time to First COPD Exacerbation |  | Baseline up to Week 24 | 
| Change From Baseline in Health-related Quality of Life as Assessed by the Overall Score of the Saint George's Respiratory Questionnaire for COPD (SGRQ-C) at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in COPD Symptoms as Measured by the Overall Score of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in Cough and Sputum as Measured by the Cough and Sputum Domain Score of the EXACT at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in Dyspnea as Assessed by the Baseline Dyspnea Index/Transition Dyspnea Index (BDI/TDI) at Week 24 |  | Baseline, Week 24 | 
| Percentage of Participants with Adverse Events And Serious Adverse Events |  | Baseline up to Week 36 | 
| Percentage of Participants with Anti-therapeutic Antibody (ATA) to Lebrikizumab |  | Baseline up to Week 36 | 
| Minimum Observed Serum Trough Lebrikizumab Concentration (Cmin) |  | Pre-dose (Hour 0) at Weeks 4 and 12, at Week 24 | 
| Plasma Decay Half-Life (t1/2) |  | Pre-dose (Hour 0) on Day 1 (Baseline) and Weeks 1, 4, 8, 12, 16, 20; at Weeks 24, 28, and 36 |