Asthma
Conditions
Brief summary
This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy, safety, and tolerability of lebrikizumab in adolescent participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroids (ICS) therapy and at least one second controller medication. Participants will be randomized in a 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ('High' or 'Low') or placebo, administered as subcutaneous (SC) every 4 weeks (Q4W) for 52 weeks, in addition to their standard-of-care therapy. This will be followed by an optional 52-week double-blind active-treatment extension. The anticipated time on study treatment is up to 104 weeks. Participants who complete the study to Week 104, discontinue prematurely or decide not to take part in the optional active-treatment extension will transition to the 20-week safety follow-up period.
Interventions
DRUGLebrikizumab
Lebrikizumab will be administered as SC injection at high or low dose Q4W.
DRUGPlacebo
Lebrikizumab matching placebo will be administered as SC injection Q4W.
DRUGStandard of Care
Participants will continue to receive ICS therapy (total daily dose of 500-2000 mcg fluticasone propionate DPI or equivalent) along with at least one second controller medications (e.g. long-acting beta agonists \[LABAs\], leukotriene receptor antagonists (LTRAs), long-acting muscarinic antagonists (LAMAs), or theophylline) as standard of care.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Asthma diagnosis for greater than or equal to (\>/=) 12 months prior to Visit 1 * Bronchodilator response during screening * Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3 * On high dose ICS therapy for \>/= 6 months prior to Visit 1 * On an eligible second controller medication for 6 months prior to Visit 1 * Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization * 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 prior to 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 that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 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 * History of active tuberculosis requiring treatment * Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection * Evidence of acute or chronic hepatitis or known liver cirrhosis * History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma * Diagnosis or history of 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 (whichever is longer) prior to Visit 1 * Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening * History of bronchial thermoplasty
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period | Baseline up to Week 52 | 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 hospitalization. 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 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52 | Week 52 | Measurement of FeNO (in parts per billion \[ppb\]) was performed using a hand-held portable NIOX MINO® device, in accordance with guidelines published by the American Thoracic Society (ATS) and described in the pulmonary function testing manual. |
| Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52 | Week 52 | The Standardized AQLQ+12 was used to assess the participants' asthma-specific health-related quality of life. The AQLQ+12 had a recall specification of 2 weeks. The AQLQ+12 was a 32-item questionnaire with 4 domains: activity limitations, symptoms, emotional function, and environmental stimuli. Each of the 32 questions were scored on a scale 1-7. The overall AQLQ+12 score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7 indicated no impairments due to asthma, and a score of 1 indicated severe impairment. |
| Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Week 52 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100. |
| Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52 | Week 52 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52. |
| Change From Baseline in Asthma Rescue Medication Use at Week 52 | Week 52 | Participants were allowed to use short-acting bronchodilators as asthma rescue medication. Baseline asthma rescue medication use was defined as the average number of puffs per day over the 7 days prior to and on the day of randomization. Participants must have recorded their asthma rescue medication use for at least 4 days to have a baseline score calculated. The post-baseline asthma medication use for any timepoint was defined as the average number of puffs per day over the last 28 days on or prior to the timepoint. Participants must have recorded their asthma rescue medication use for at least 14 days during a 28-day interval to have a score calculated for the respective timepoint. For nebulizer use, one treatment (inhalation) was considered equivalent to 4 puffs. |
| Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events | Baseline up to Week 52 | Urgent asthma-related HCU events included hospitalizations, emergency department visits, and acute care visits. Rate of urgent asthma-related HCU events = total number of urgent asthma-related HCU events divided by total follow-up time in patient years. |
| Injection Acceptability Questionnaire (IAQ) Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | The acceptability of the injections of study drug was addressed by measuring the level of pain that participants experienced. Participants assessed pain associated with study drug administration using the IAQ within 10 minutes of study drug administration. The IAQ score ranged from 0 to 10; where 0 = no pain and 10 = worst pain imaginable. |
| Time to First Asthma Exacerbation | Baseline up to Week 52 | An asthma exacerbation was 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 hospitalization. Treatment with systemic corticosteroids was defined as treatment with oral, IV, or IM corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Median time to first protocol-defined asthma exacerbation was estimated using Kaplan-Meier analysis. 95% Confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. |
| Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab | Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52 | Participants who received at least one dose of lebrikizumab and had at least one post-baseline evaluable sample were included in the analysis. Results of post-dose samples which were less than reportable were set to 0.045 micrograms per milliliter (mcg/mL) that is half of minimum quantifiable concentration value (0.09 mcg/mL). |
Countries
Argentina, Brazil, Canada, Colombia, Czechia, France, Germany, Hungary, Israel, Italy, Mexico, Peru, Poland, Portugal, Slovakia, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Pre-assignment details
A total of 579 participants were screened for the study of which 346 were randomized and received at least one dose of study drug.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 1.6 |
| Age group (years) 12 to 14 | 71 Participants |
| Age group (years) 15 to 17 | 49 Participants |
| Baseline Use of Inhaled Corticosteroid (ICS) and Long-Acting Beta-Agonist (LABA) ICS >= 1000 µg/day and LABA | 25 Participants |
| Baseline Use of Inhaled Corticosteroid (ICS) and Long-Acting Beta-Agonist (LABA) ICS < 1000 µg/day or no LABA | 88 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 229 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Asthma Exacerbations in Last 12 Months | 1.6 Asthma Exacerbations STANDARD_DEVIATION 2.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants |
| Race (NIH/OMB) White | 75 Participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 57 Participants |
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 | 0 / 56 | 0 / 113 | 0 / 116 | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 23 / 56 | 67 / 113 | 72 / 116 | 23 / 30 | 24 / 31 |
| serious Total, serious adverse events | 3 / 56 | 6 / 113 | 8 / 116 | 3 / 30 | 4 / 31 |
Outcome results
None listed