Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
Phase II, randomized, double-blind, placebo-controlled, parallel-group clinical trial of lebrikizumab in participants with COPD and a history of exacerbations who are treated with inhaled corticosteroid (ICS) and at least one long-acting bronchodilator inhaler medication. This study will be conducted to assess the safety, efficacy, and patient-reported outcome (PRO) measures.
Interventions
DRUGLebrikizumab
Lebrikizumab 125 milligrams (mg) will be administered subcutaneously once in every 4 weeks.
DRUGPlacebo
Matching placebo will be administered subcutaneously once in every 4 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Documented history of COPD greater than or equal to (\>/=) 12 months prior to Visit 1 * Post-bronchodilator FEV1/FVC less than (\<) 0.70 at Visit 1 or 2 * Post bronchodilator FEV1 \<80% predicted at Visit 1 or 2 * Documented history of one or more acute COPD exacerbations requiring treatment with systemic corticosteroids and/or antibiotics or hospitalization within 12 months prior to Visit 1 * Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking \>/=10 pack-years (20 cigarettes/day for 10 years) * On inhaled corticosteroids (ICS) therapy for \>/=6 months prior to Visit 1 * On an eligible bronchodilator medication for \>/=6 months prior to Visit 1 * Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray prior to Visit 2 that confirms absence of clinically significant lung disease besides COPD * Demonstrated adherence with background COPD inhaler medication during screening period * For female participants of childbearing age, use of single or combined contraceptive methods for the duration of the study
Exclusion criteria
* History of severe allergic reaction or anaphylactic reaction to biologic agent or known hypersensitivity to lebrikizumab injection * History of clinically significant pulmonary disease other than COPD * Diagnosis of alpha-1-antitrypsin deficiency * Lung volume reduction surgery or procedure within 12 months prior to Visit 1 * Supplemental oxygen requirement \>2 liters/minute (L/min) at rest or with exertion * Current diagnosis of asthma * Participants participating in, or scheduled for, an intensive COPD rehabilitation program * Maintenance oral corticosteroid therapy * Treatment with systemic corticosteroids within 4 weeks prior to Visit 1 or during screen period * Unstable ischemic heart disease or other relevant cardiovascular disorders * Use of an immunomodulatory or immunosuppressive therapy including monoclonal antibodies (includes anti-interleukin-13 (IL) or anti-IL-4/IL-13 therapy) * Body weight \<40 kg * Any infection that resulted in hospital admission for \>/= 24 hours and/or treatment with oral, 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 or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening * Received a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening * Active tuberculosis requiring treatment within 12 months prior to Visit 1 * Human immunodeficiency virus (HIV) or other known immunodeficiency * Hepatitis or known liver cirrhosis * Aspartate Aminotransferase (AST), Alanine Aminotransferase (ATL), or total bilirubin elevation \>/=2.0 x upper limit of normal (ULN) during screening * Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests * History of alcohol or drug abuse * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 12 | Baseline, Week 12 | Adjusted mean change from baseline in pre-bronchodilator FEV1 (assessed using spirometry) at Week 12 was calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Moderate or Severe COPD Exacerbation | Baseline up to Week 24 | A moderate COPD exacerbation was defined as new or increased COPD symptoms (for example, dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation was defined as new or increased COPD symptoms (for example, dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days that lead to hospitalization. Adjusted exacerbation rate per year was calculated. Results are reported as a 'Number' representing the unadjusted annualized rate of COPD exacerbations per person-year. The total number of exacerbations observed during the period was defined as starting at the date of randomization and ending at most 172 days after randomization (including data collected during safety follow-up in the case of early drug discontinuation) regardless of adherence to study drug divided by the total patient-weeks at risk divided by 52 weeks per year. |
| Change From Baseline in Post-bronchodilator FEV1 at Week 24 | Baseline, Week 24 | Adjusted mean change from baseline in post-bronchodilator FEV1 at Week 24 was calculated. |
| Change From Baseline in Pre-bronchodilator FEV1 at Week 24 | Baseline, Week 24 | Adjusted mean change from baseline in pre-bronchodilator FEV1 at Week 24 was calculated. |
| Time to First COPD Exacerbation | Baseline up to Week 24 | COPD exacerbation was defined as new or increased COPD symptoms (for example, dyspnea, sputum volume, and sputum purulence) for at least 2 consecutive days. Time to first COPD exacerbation was estimated using Kaplan-Meier analysis. |
| Change From Baseline in Health-Related Quality of Life as Assessed by the Overall Score of the Saint George's Respiratory Questionnaire for COPD (SGRQ-C) at Week 24 | Baseline, Week 24 | SGRQ-C was assessed by asking participants to recall their COPD-related experiences and to respond to 40 questions included within three domains: symptoms (7 items), activity (13 items), and impacts (20 items). Overall SGRQ-C score ranged from 0 to 100, where lower score indicated better health-related quality of life. Change from baseline in overall SGRQ-C score at Week 24 was reported. |
| Change From Baseline in COPD Symptoms as Measured by the Overall Score of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) at Week 24 | Baseline, Week 24 | EXACT comprised of 14-item questionnaire containing four domains: breathlessness (5 items), cough and sputum (3 items), chest symptoms (3 items), and additional attributes (3 items). Overall EXACT score was the average of domain scores. It ranged from 0 to 100, where higher score indicated a more severe condition. Change from baseline in overall EXACT score at Week 24 was reported. |
| Change From Baseline in Cough and Sputum as Measured by the Cough and Sputum Domain Score of the EXACT at Week 24 | Baseline, Week 24 | EXACT comprised of 14-item questionnaire containing four domains: breathlessness (5 items), cough and sputum (3 items), chest symptoms (3 items), and additional attributes (3 items). Cough and Sputum domain score ranged from 0 to 100, where higher score indicated a more severe condition. Change from baseline in cough and sputum domain EXACT score at Week 24 was reported. |
| Change From Baseline in Dyspnea as Assessed by the Baseline Dyspnea Index/Transition Dyspnea Index (BDI/TDI) at Week 24 | Baseline, Week 24 | The BDI scores ranged from 0 (very severe impairment) to 4 (no impairment) for each of 3 domains (functional impairment, magnitude of task, and magnitude of effort) and were summed to determine the BDI total score (0 to 12). The TDI scores ranged from -3 (major deterioration) to +3 (major improvement) for each of the 3 domains (functional impairment, magnitude of task, and magnitude of effort). The sum of all domains yielded the TDI total score (-9 to +9). Change from baseline in BDI/TDI at Week 24 was reported. |
| Percentage of Participants With Anti-Therapeutic Antibody (ATA) to Lebrikizumab | Baseline up to Week 36 | This outcome measure was planned to be analyzed only in overall lebrikizumab arm. |
| Minimum Observed Serum Trough Concentration (Cmin) of Lebrikizumab | Pre-dose (Hour 0) at Weeks 4 and 12, at Week 24 | This outcome measure was planned to be analyzed only in overall lebrikizumab arm. |
| Elimination Half-Life (t1/2) of Lebrikizumab | Pre-dose (Hour 0) on Day 1 (Baseline) and Weeks 1, 4, 12, 24, 28, and 36 | Elimination half-life was defined as the time measured for the serum concentration to decrease by one half. This outcome measure was planned to be analyzed only in overall lebrikizumab arm. |
Countries
Argentina, Bulgaria, Canada, Denmark, Hungary, Mexico, Poland, Russia, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Pre-assignment details
A total of 391 participants were screened of which 309 participants were randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 140 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 0 Participants |
| Race (NIH/OMB) White | 289 Participants |
| Sex: Female, Male Female | 116 Participants |
| Sex: Female, Male Male | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 154 | 1 / 155 |
| other Total, other adverse events | 66 / 154 | 57 / 155 |
| serious Total, serious adverse events | 23 / 154 | 21 / 155 |
Outcome results
None listed