Asthma
Conditions
Keywords
Asthma, Reactive Airways, Respiratory Tract Disease, Obstructive Tract Disease, Lung Diseases
Brief summary
A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, 12-Week, Phase 2 Study to Evaluate the Effect of Tralokinumab on Airway Inflammation in Adults with Asthma Inadequately Controlled on Inhaled Corticosteroid.
Detailed description
This is a multicentre, randomized, double-blind, parallel group, placebo-controlled, phase 2 study to designed evaluate the effect of a 300 mg dose of tralokinumab administered subcutaneously every 2 weeks on airway inflammation in adults with asthma inadequately controlled on inhaled corticosteroids (ICS) with or without other controllers. Approximately 80 subjects will be randomized. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 12 week treatment period.
Interventions
BIOLOGICALTralokinumab
Subcutaneous Injection
OTHERPlacebo
Subcutaneous Injection
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years 2. Documented physician-diagnosed asthma for at least 12 months prior to enrolment (v1) 3. Documented treatment with an asthma controller regimen requiring treatment with ICS (minimum dose of ≥ 250 ug fluticasone propionate via dry powder inhaler equivalents total daily dose) alone or in combination ≥ 6 months and that has been taken at a stable dose for at least 1 month prior to enrolment (v1) 4. Additional maintenance asthma controller medications must be given at a stable dose for at least 1 month prior to v1. 5. At enrolment (v1) the subject must have a predicted normal value (PNV) for the pre-bronchodilator (BD) FEV1\>50% and more than 1L. 6. Post-BD reversibility in FEV1 of ≥12% and ≥200 mL at enrolment (v1).
Exclusion criteria
1. History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma. 2. History of anaphylaxis following any biologic therapy. 3. Hepatitis B, C or HIV 4. Pregnant or breastfeeding 5. History of cancer 6. Current tobacco smoking or a history of tobacco smoking for \>10 pack-years. 7. Previous receipt of tralokinumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils | Baseline (Week 0) and Week 12 | The number of airway submucosal eosinophils per millimetre squared (mm\^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils | Baseline (Week 0) and Week 12 | The blood eosinophil count was obtained from the total and differential white blood cell counts. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of blood eosinophils is presented as geometric mean ± SD of log values. |
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils | Baseline (Week 0) and Week 12 | Sputum induction was performed to obtain satisfactory samples of sputum originating from the airways. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of eosinophils in induced sputum is presented as geometric mean ± SD of log values. |
| Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations | Baseline (Week 0) and Week 12 | ECP concentrations were determined to assess evidence of activation of eosinophils in blood. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in blood free ECP concentrations is presented as geometric mean ± SD of log values. |
| Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations | Baseline (Week 0) and Week 12 | ECP concentrations were determined to assess evidence of activation of eosinophils in sputum. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in sputum free ECP concentrations is presented as geometric mean ± SD of log values. |
Countries
Canada, Denmark, United Kingdom
Participant flow
Recruitment details
First patient enrolled: 29 Sep 2015; Last patient last visit: 21 Jun 2017. Study performed at 14 sites in 3 countries. Patients maintained on currently prescribed inhaled corticosteroid (≥250 micrograms fluticasone dry powder formulation equivalents total daily dose) + any additional maintenance asthma controller medication throughout the study.
Pre-assignment details
79 patients were randomised to receive investigational product (IP) and all those randomised received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Tralo 300 mg Q2W Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). | 39 |
| Placebo Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). | 40 |
| Total | 79 |
Baseline characteristics
| Characteristic | Placebo | Total | Tralo 300 mg Q2W |
|---|---|---|---|
| Age, Continuous | 50.1 Years STANDARD_DEVIATION 14.2 | 48.6 Years STANDARD_DEVIATION 14.2 | 47.1 Years STANDARD_DEVIATION 14.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 73 Participants | 34 Participants |
| Sex: Female, Male Female | 20 Participants | 43 Participants | 23 Participants |
| Sex: Female, Male Male | 20 Participants | 36 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 30 / 39 | 27 / 40 |
| serious Total, serious adverse events | 0 / 39 | 1 / 40 |
Outcome results
Primary
Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils
The number of airway submucosal eosinophils per millimetre squared (mm\^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values.
Time frame: Baseline (Week 0) and Week 12
Population: The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tralo 300 mg Q2W | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils | 1.29 Ratio | Standard Deviation 2.06 |
| Placebo | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils | 1.07 Ratio | Standard Deviation 1.87 |
Comparison: Comparison of change from baseline, expressed as a ratio, in airway submucosal eosinophils; Tralo 300 mg Q2W vs placebo. The null hypothesis was that the change in airway submucosal eosinophils at Week 12 on tralokinumab was equal to the corresponding change on placebo.p-value: 0.386295% CI: [0.63, 3.27]ANCOVA
Secondary
Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations
ECP concentrations were determined to assess evidence of activation of eosinophils in blood. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in blood free ECP concentrations is presented as geometric mean ± SD of log values.
Time frame: Baseline (Week 0) and Week 12
Population: The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tralo 300 mg Q2W | Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations | 1.07 Ratio | Standard Deviation 0.4 |
| Placebo | Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations | 0.92 Ratio | Standard Deviation 0.47 |
Comparison: Comparison of change from baseline, expressed as a ratio, in blood free ECP concentration; Tralo 300 mg Q2W vs placebo.p-value: 0.376995% CI: [0.88, 1.4]Repeated measures analysis
Secondary
Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils
The blood eosinophil count was obtained from the total and differential white blood cell counts. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of blood eosinophils is presented as geometric mean ± SD of log values.
Time frame: Baseline (Week 0) and Week 12
Population: The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tralo 300 mg Q2W | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils | 1.10 Ratio | Standard Deviation 0.38 |
| Placebo | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils | 0.91 Ratio | Standard Deviation 0.46 |
Comparison: Comparison of change from baseline, expressed as a ratio, in blood eosinophil count; Tralo 300 mg Q2W vs placebo.p-value: 0.054695% CI: [1, 1.48]Repeated measures analysis
Secondary
Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils
Sputum induction was performed to obtain satisfactory samples of sputum originating from the airways. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of eosinophils in induced sputum is presented as geometric mean ± SD of log values.
Time frame: Baseline (Week 0) and Week 12
Population: The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tralo 300 mg Q2W | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils | 0.20 Ratio | Standard Deviation 3.16 |
| Placebo | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils | 0.47 Ratio | Standard Deviation 3.63 |
Comparison: Comparison of change from baseline, expressed as a ratio, in differential sputum eosinophils; Tralo 300 mg Q2W vs placebo.p-value: 0.633495% CI: [0.06, 6]Repeated measures analysis
Secondary
Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations
ECP concentrations were determined to assess evidence of activation of eosinophils in sputum. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in sputum free ECP concentrations is presented as geometric mean ± SD of log values.
Time frame: Baseline (Week 0) and Week 12
Population: The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tralo 300 mg Q2W | Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations | 0.66 Ratio | Standard Deviation 1.21 |
| Placebo | Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations | 1.83 Ratio | Standard Deviation 1.41 |
Comparison: Comparison of change from baseline, expressed as a ratio, in sputum free ECP concentration; Tralo 300 mg Q2W vs placebo.p-value: 0.112695% CI: [0.2, 1.2]Repeated measures analysis