Inadequately Controlled Asthma
Conditions
Keywords
open-label study, tralokinumab, subcutaneous, inadequately controlled asthma, asthma, medium to high-dose of inhaled corticosteroid, long-acting β2-agonist
Brief summary
A 52-Week, Open-Label, Multicentre Study to Evaluate the Safety of Tralokinumab in Japanese Adults and Adolescents with Asthma Inadequately Controlled on Inhaled Corticosteroid plus Long-Acting β2-Agonist
Detailed description
This is a 52-week, open-label, multi-centre study designed to evaluate the safety of tralokinumab in a fixed 300 mg dose every 2 weeks, administered subcutaneously in adults and adolescents with indequately controlled asthma on medium to high dose inhaled corticosteroid plus long acting β-2 antagonist. Approximately 26 Japanese subjects will be recruited to receive 22 completed.
Interventions
BIOLOGICALTralokinumab open-label
Subcutaneous injection; fixed dose; 300 mg
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 12 - 75 yrs 2. Documented physician-diagnosed asthma 3. Documented treatment with inhaled corticosteroid (ICS) at a total daily dose corresponding to ≥500 µg fluticasone propionate dry powder formulation equivalents and a long-acting beta-2 agonist (LABA) 4. Pre-bronchodilator (BD) forced expiratory volume at one second (FEV1) value of ≥40% of their Predicted Normal Value (PNV) 5. Asthma Control Questionnaire-6 (ACQ-6) score ≥1.5
Exclusion criteria
1. Pulmonary disease other than asthma 2. History of anaphylaxis following any biologic therapy 3. Hepatitis B, C or HIV 4. Pregnant of breastfeeding 5. History or cancer 6. Current tobacco smoking or a history or tobacco smoking for ≥10 pack-years 7. Previous receipt of tralokinumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). | An AE was development of an undesirable medical condition or deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to product. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. In clinical studies, an AE can include an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment has been administered. A SAE was an AE occurred during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening, in-patient or prolongation of existing hospitalization; persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions; congenital abnormality or birth defect; important medical event that may jeopardise participant or may require medical intervention to prevent one of the outcomes listed above. |
| Number of Participants With Clinical Laboratory Abnormalities | From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). | Blood and urine samples for determination of clinical chemistry, haematology and urinalysis parameters were taken at the times. Changes in haematology and clinical chemistry variables between baseline and each subsequent scheduled assessment were evaluated. Baseline is defined as the last available value measured prior to the first dose of study treatment. The change from baseline is defined as the treatment period value minus the baseline period value. Absolute values were compared to the relevant reference range and classified as low (below range), normal (within range or on limits) or high (above range). The AstraZeneca extended reference ranges were used for laboratory variables (where they exist). All values (absolute and change) falling outside the reference ranges were flagged. Urinalysis data were categorised as negative (0), trace or positive (+) at each time point. |
| Number of Participants With Abnormal Physical Examinations | From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). | Physical examination included assessment of general appearance, skin, head and neck (including eyes, ears, nose, mouth and throat), lymph nodes, abdomen, musculoskeletal (including spine and extremities), cardiovascular, respiratory, and neurological systems. Criteria for abnormal physical findings were based on investigator's discretion. |
| Number of Participants With Vital Signs Abnormalities | From Screening (Day -14) up to 14 weeks after end of treatment (Week 66). | Vital signs that were planned to be assessed included parameters such as pulse, systolic blood pressure, diastolic blood pressure, respiration rate and body temperature. |
| Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities | At Day -14 and Week 52. | The ECG assessments were performed using an ECG device prior to blood drawing, spirometry, investigational product administration and bronchodilator administration. ECG data and evaluation was planned to be performed by the site Investigator. |
Countries
Japan
Participant flow
Recruitment details
Adult participants with asthma inadequately controlled on inhaled corticosteroid plus long-acting beta 2 agonist were recruited at 4 sites in Japan from 01 November 2016 until study termination on 24 January 2018. No adolescent participants were enrolled in the study.
Pre-assignment details
Of all enrolled participants, 3 were considered screen failures and 28 participants were received study treatment. Following initial screening, there was a run-in period of up to 2 weeks to allow adequate time for eligibility criteria to be evaluated prior to entry to planned 52-week treatment period followed by a 14 week extended follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| Tralokinumab 300 mg Every 2 Weeks (Q2W) Participants were administered with tralokinumab 300 mg subcutaneous injection every 2 weeks for 52 weeks. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discontinuation of asthma program | 28 |
Baseline characteristics
| Characteristic | Tralokinumab 300 mg Every 2 Weeks (Q2W) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 47.7 Years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 0 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 21 / 28 |
| serious Total, serious adverse events | 1 / 28 |
Outcome results
Primary
Number of Participants With 12-Lead Electrocardiogram (ECG) Abnormalities
The ECG assessments were performed using an ECG device prior to blood drawing, spirometry, investigational product administration and bronchodilator administration. ECG data and evaluation was planned to be performed by the site Investigator.
Time frame: At Day -14 and Week 52.
Population: The study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. No summary table was developed.
Primary
Number of Participants With Abnormal Physical Examinations
Physical examination included assessment of general appearance, skin, head and neck (including eyes, ears, nose, mouth and throat), lymph nodes, abdomen, musculoskeletal (including spine and extremities), cardiovascular, respiratory, and neurological systems. Criteria for abnormal physical findings were based on investigator's discretion.
Time frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Population: The study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. Any new finding(s) or aggravated existing finding(s), judged as clinically significant by the Investigator, were reported as an AE.
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was development of an undesirable medical condition or deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to product. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. In clinical studies, an AE can include an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment has been administered. A SAE was an AE occurred during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening, in-patient or prolongation of existing hospitalization; persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions; congenital abnormality or birth defect; important medical event that may jeopardise participant or may require medical intervention to prevent one of the outcomes listed above.
Time frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Population: The safety analysis set included all participants enrolled and who received at least 1 dose of investigational product irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tralokinumab 300 mg Every 2 Weeks (Q2W) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 21 Participants |
| Tralokinumab 300 mg Every 2 Weeks (Q2W) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE with outcome of death | 0 Participants |
| Tralokinumab 300 mg Every 2 Weeks (Q2W) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE (including events with outcome of death) | 1 Participants |
| Tralokinumab 300 mg Every 2 Weeks (Q2W) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE leading to discontinuation of study drug | 1 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities
Blood and urine samples for determination of clinical chemistry, haematology and urinalysis parameters were taken at the times. Changes in haematology and clinical chemistry variables between baseline and each subsequent scheduled assessment were evaluated. Baseline is defined as the last available value measured prior to the first dose of study treatment. The change from baseline is defined as the treatment period value minus the baseline period value. Absolute values were compared to the relevant reference range and classified as low (below range), normal (within range or on limits) or high (above range). The AstraZeneca extended reference ranges were used for laboratory variables (where they exist). All values (absolute and change) falling outside the reference ranges were flagged. Urinalysis data were categorised as negative (0), trace or positive (+) at each time point.
Time frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Population: No participants were analysed as the study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings of clinical laboratory parameters were evaluated for safety signal.
Primary
Number of Participants With Vital Signs Abnormalities
Vital signs that were planned to be assessed included parameters such as pulse, systolic blood pressure, diastolic blood pressure, respiration rate and body temperature.
Time frame: From Screening (Day -14) up to 14 weeks after end of treatment (Week 66).
Population: The study was terminated due to discontinuation of tralokinumab asthma program. Study was reported in a synopsis format. Individual listings were evaluated for safety signal. No summary table was developed.