A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma

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 of lebrikizumab compared with placebo, as measured by the ability of participants to achieve lower daily doses of OCS, among those with severe corticosteroid-dependent asthma. Prednisone/prednisolone will be the OCS therapy prescribed. Participants will be randomized to receive lebrikizumab or matching placebo for 44 weeks in a double-blind, placebo-controlled (DBPC) period. Those who complete the 44-week period may continue into a 32-week active treatment extension (ATE) period, during which all participants will receive lebrikizumab treatment. Following completion of the ATE period, participants who have both tolerated and derived benefit from treatment with lebrikizumab may continue their lebrikizumab treatment into a long-term extension (LTE) period. Participants will transition to 24 weeks of safety follow-up upon discontinuation of study drug.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo Controlled, Multicenter Trial to Assess the Oral Corticosteroid-Sparing Effect of Lebrikizumab in Patients With Severe Corticosteroid Dependent Asthma

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: Severe asthma despite intensive follow-up by an asthma specialist for >/=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 micrograms (mcg) beclomethasone dipropionate 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 OCS for >/=6 months prior to Visit 1 Assessment to ensure diagnosis of refractory asthma and OCS dependence on minimal effective or maximum tolerated dose prior to Visit 1 with compliance 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 For adolescents: History of active tuberculosis requiring treatment 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 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 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 more than 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-interleukin (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 a live attenuated vaccine throughout the study

Ages Eligible for Study
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Minimum Age: 12 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 High Dose<br>Participants will receive lebrikizumab at high dose level as subcutaneous (SC) injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.<br>* Other names: RO5490255;|
| Experimental: Lebrikizumab Low Dose<br>Participants will receive lebrikizumab at low dose level as SC injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.<br>* Other names: RO5490255;|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to lebrikizumab SC injection every 4 weeks during the 44-week DBPC period. Participants will then be randomized to receive either high- or low-dose lebrikizumab every 4 weeks during the 32-week ATE period and will continue same treatment in the LTE period. | Drug: Lebrikizumab<br>* Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.<br>* Other names: RO5490255;Drug: Placebo<br>* Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in Daily OCS Dose at Week 44 |  | Baseline, Week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Daily OCS Dose at Week 44 |  | Baseline, Week 44 | 
| Relative Change From Week 12 in Average OCS Dose at Week 44 |  | Week 12, Week 44 | 
| Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline |  | Baseline, Week 44 | 
| Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44 | Percentage of participants discontinuing OCS therapy or having achieved adrenal maintenance dose (cortisol level less than or equal to 100 nanomoles per liter) will be reported. | Week 44 | 
| Percentage of Participants With Asthma Exacerbations | An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, or nocturnal awakenings due to these symptoms) that lead to treatment with systemic corticosteroids greater than or equal to (>/=) 30 milligrams (mg) or 0.5 mg per kilogram (kg) for >/=3 consecutive days or to hospitalization. | Baseline up to Week 44 | 
| Percentage of Participants With Adverse Events |  | Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years) | 
| Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab |  | Predose (0 hours) at Weeks 0, 4, 12, 24, 36, 44, 52, 64, and 76, at early discontinuation (up to a minimum of approximately 2 years), and at 24 weeks after last dose administration (up to a minimum of approximately 2 years) | 
| Minimum Observed Serum Lebrikizumab Concentration (Cmin) |  | Predose (0 hours) at Weeks 4, 12, 24, 36, and 44 |