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 as subcutaneous (SC) injection 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. Participants who were assigned to placebo during the placebo-controlled period of the trial will be re-randomized at Week 52 to receive blinded SC lebrikizumab 37.5 milligrams (mg) or 125 mg every 4 weeks from Weeks 53 to 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 at 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 microgram (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 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 |
|---|---|
| Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period | Baseline up to Week 52 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events | Baseline up to Week 124 |
| Change from Baseline In Asthma Rescue Medication (Number of Puffs or Nebulized Treatments) | Baseline, Week 52 |
| Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Baseline, Week 52 |
| Time to First Asthma Exacerbation | Baseline up to Week 52 |
| Rate of Urgent Asthma-Related Urgent Health Care Utilization | Baseline up to Week 52 |
| Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab | Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 64, 76, 92, 104, 112, and 124) |
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score | Baseline, Week 52 |
| Minimum Serum Concentration (Cmin) of Lebrikizumab | Predose (0 hour) on Weeks 4, 12, 24, 36, and 52 |
| Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score | Baseline, Week 52 |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Mexico, New Zealand, Peru, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States
Outcome results
None listed