Brief Summary
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 subcutaneously (SC) 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. During double-blind active treatment extension period, all participants will receive SC injection of lebrikizumab from Week 53 to Week 104. The anticipated time on study treatment is 104 weeks. After study treatment, all participants will complete a 20-week safety follow-up.
Brief Title
A Study of Lebrikizumab in Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication
Completion Date
Completion Date Type
Actual
Conditions
ASTHMA
Eligibility Criteria
Inclusion Criteria:
* Asthma diagnosis for greater than equal to (\>/=) 12 months prior to 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 micrograms (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 infection that required treatment with oral antibiotics within 2 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
* Asthma diagnosis for greater than equal to (\>/=) 12 months prior to 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 micrograms (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 infection that required treatment with oral antibiotics within 2 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
Inclusion Criteria
Inclusion Criteria:
* Asthma diagnosis for greater than equal to (\>/=) 12 months prior to 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 micrograms (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
* Asthma diagnosis for greater than equal to (\>/=) 12 months prior to 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 micrograms (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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT01867125
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
GB28688
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
Asthma exacerbation is defined as new or increased asthma symptoms (i.e., wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to systemic corticosteroid (CS) treatment (oral, intravenous (IV), or intramuscular (IM) CS for ≥ 3 days or an emergency department visit with at least one dose of IV or IM CS) or to hospitalization.
Results are reported as a 'Number' representing the model-adjusted incidence rate of asthma exacerbations per person-year. To account for early discontinuation, for each patient, the time at risk (in years) was computed as the duration of this time period (last day minus first day \[in days\] plus 1) divided by 365.25. The 'first day' was the day of randomization to the PCP. For patients entering the ATE, the 'last day' was the day prior to ATE randomization. For patients not entering the ATE, the 'last day' was at the last study visit on/prior to Study Day 379 (365 days plus a 14-day window).
Results are reported as a 'Number' representing the model-adjusted incidence rate of asthma exacerbations per person-year. To account for early discontinuation, for each patient, the time at risk (in years) was computed as the duration of this time period (last day minus first day \[in days\] plus 1) divided by 365.25. The 'first day' was the day of randomization to the PCP. For patients entering the ATE, the 'last day' was the day prior to ATE randomization. For patients not entering the ATE, the 'last day' was at the last study visit on/prior to Study Day 379 (365 days plus a 14-day window).
Outcome Measure
Adjusted Exacerbation Rate of Asthma During the 52-Week PCP
Outcome Time Frame
Baseline up to 52 weeks
Secondary Ids
Secondary Id
2013-000175-33
Secondary Outcomes
Outcome Description
FEV1 is the maximal amount of air, which can be forcefully exhaled in one second. Measurements were performed before use of bronchodilator. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52.
Outcome Time Frame
Week 52
Outcome Measure
Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52
Outcome Description
An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalisation. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least one dose of IV or IM corticosteroids. Reported is the time to first asthma exacerbation during the 52-week placebo-controlled period.
Outcome Time Frame
Baseline up to 52 weeks
Outcome Measure
Time to First Asthma Exacerbation During the 52-week PCP
Outcome Description
Urgent health care utilization was defined as hospitalizations, emergency department visits, and acute care visits.
Results are reported as a 'Number' representing the model-adjusted incidence rate of urgent asthma-related HCU events per person-year. To account for early discontinuation, for each patient, the time at risk (in years) was computed as the duration of this time period (last day minus first day \[in days\] plus 1) divided by 365.25. The 'first day' was the day of randomization to the PCP. For patients entering the ATE, the 'last day' was the day prior to ATE randomization. For patients not entering the ATE, the 'last day' was at the last study visit on/prior to Study Day 379 (365 days plus a 14-day window).
Results are reported as a 'Number' representing the model-adjusted incidence rate of urgent asthma-related HCU events per person-year. To account for early discontinuation, for each patient, the time at risk (in years) was computed as the duration of this time period (last day minus first day \[in days\] plus 1) divided by 365.25. The 'first day' was the day of randomization to the PCP. For patients entering the ATE, the 'last day' was the day prior to ATE randomization. For patients not entering the ATE, the 'last day' was at the last study visit on/prior to Study Day 379 (365 days plus a 14-day window).
Outcome Time Frame
Baseline up to Week 52
Outcome Measure
Rate of Urgent Asthma-Related Health Care Utilization (HCU) During the 52-week PCP
Outcome Description
Asthma-specific health-related quality of life was assessed by the overall score of the Standardized AQLQ. The AQLQ is a self-administered test with 32 questions; each with seven possible answers ranging from 1 to 7 with a higher score being more favorable. Total score is calculated as follows: sum of items 1to 32 divided by 32 for a score range of 1 to 7 with a higher score indicating a better outcome. Reported is the change in AQLQ score from baseline to the end of the placebo-controlled period at Week 52.
Outcome Time Frame
Week 52
Outcome Measure
Absolute Change From Baseline in Standardized AQLQ Score at Week 52
Outcome Description
Reported here is the change in the number of puffs or nebulized treatments of asthma rescue medication from baseline to the end of the PCP at Week 52.
Outcome Time Frame
Week 52
Outcome Measure
Absolute Change From Baseline In Asthma Rescue Medication Use at Week 52
Outcome Description
The ACQ-5 is test with 5 questions; each with seven possible answers ranging from 0 to 6 with a lower score being more favorable. Total score range is 0 to 30 with a lower score indicating a better outcome. Reported is the change in ACQ-5 score from baseline to the end of the PCP at Week 52.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Absolute Change From Baseline in ACQ-5 Score at Week 52
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Golda Hudes
Investigator Email
ghudes@montefiore.org
Investigator Phone
646-229-9509
Categories Mesh Debug
Asthma and Other Respiratory Diseases --- BRONCHIAL DISEASES
Lung --- BRONCHIAL DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Lung --- LUNG DISEASES, OBSTRUCTIVE
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY HYPERSENSITIVITY
Lung --- RESPIRATORY HYPERSENSITIVITY
Immune System --- IMMUNE SYSTEM DISEASES
MeSH Terms
ASTHMA
BRONCHIAL DISEASES
RESPIRATORY TRACT DISEASES
LUNG DISEASES, OBSTRUCTIVE
LUNG DISEASES
RESPIRATORY HYPERSENSITIVITY
HYPERSENSITIVITY, IMMEDIATE
HYPERSENSITIVITY
IMMUNE SYSTEM DISEASES
LEBRIKIZUMAB