Asthma
Conditions
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.
Interventions
DRUGLebrikizumab
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.
DRUGPlacebo
Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Exacerbation Rate of Asthma During the 52-Week PCP | Baseline up to 52 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52 | Week 52 | 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. |
| Time to First Asthma Exacerbation During the 52-week PCP | Baseline up to 52 weeks | 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. |
| Rate of Urgent Asthma-Related Health Care Utilization (HCU) During the 52-week PCP | Baseline up to Week 52 | 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). |
| Absolute Change From Baseline in Standardized AQLQ Score at Week 52 | Week 52 | 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. |
| Absolute Change From Baseline In Asthma Rescue Medication Use at Week 52 | Week 52 | 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. |
| Absolute Change From Baseline in ACQ-5 Score at Week 52 | Baseline, Week 52 | 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. |
Countries
Argentina, Australia, Belgium, Canada, Chile, Colombia, Czechia, France, Hungary, Israel, Italy, Japan, Mexico, New Zealand, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
Participants with asthma, whose disease remained uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication, were recruited in 26 countries.
Pre-assignment details
Randomization (1:1:1) to the 52-week Placebo-Controlled Period (PCP) was stratified by baseline periostin level, country, asthma exacerbation and medication history. Upon PCP completion, participants entered a 52-week Active-Treatment Extension. Active groups continued their assigned lebrikizumab dose through Week 104. Participants in the Placebo group were re-randomized (1:1) to receive either 37.5 milligrams (mg) or 125 mg lebrikizumab through Week 104, stratified by baseline periostin level.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 13.2 |
| Asthma Control Questionnaire-5 (ACQ-5) Score | 2.67 Score on scale STANDARD_DEVIATION 0.72 |
| Baseline Use of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) ICS ≥ 1000 µg/day and LABA | 480 Participants |
| Baseline Use of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) ICS < 1000 µg/day or no LABA | 135 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 132 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 949 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of asthma exacerbations in last 12 months | 1.3 Exacerbations STANDARD_DEVIATION 1.5 |
| Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 1826 mL STANDARD_DEVIATION 566 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 40 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) White | 94 Participants |
| Sex: Female, Male Female | 162 Participants |
| Sex: Female, Male Male | 89 Participants |
| Standardized Asthma Quality of Life Questionnaire (AQLQ) Score | 4.23 Score on scale STANDARD_DEVIATION 0.96 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 362 | 0 / 159 | 0 / 157 | 0 / 360 | 0 / 359 |
| other Total, other adverse events | 240 / 362 | 92 / 159 | 96 / 157 | 279 / 360 | 282 / 359 |
| serious Total, serious adverse events | 32 / 362 | 14 / 159 | 16 / 157 | 48 / 360 | 49 / 359 |
Outcome results
None listed