Asthma
Conditions
Keywords
Asthma, Tralokinumab, CAT-354
Brief summary
The purpose of this study is to determine whether the addition of tralokinumab to standard asthma medication is effective in the treatment of adults with asthma.
Detailed description
Interleukin-13 (IL-13) is a key mediator in the pathogenesis of established asthmatic disease. Tralokinumab is a human monoclonal antibody that blocks IL-13, which may result in improved control of asthma. This study will determine whether the addition of tralokinumab to standard asthma medications results in a reduced rate of asthma exacerbations in subjects with severe asthma.
Interventions
OTHERPlacebo Q2W
Participants who received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks.
BIOLOGICALTralokinumab 300 mg, Q2W
Participants received tralokinumab 300 mg subcutaneous injection Q2W for a total of 26 doses up to 50 weeks.
OTHERPlacebo, Q2/4W
Participants received matching placebo subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.
BIOLOGICALTralokinumab 300 mg, Q2/4W
Participants received tralokinumab 300 mg subcutaneous injection Q2W for 12 weeks followed by Q4W for 38 weeks (Q2/4W) for a total of 16 doses.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years * Body mass index (BMI) between 16-40 kilogram per square meter (kg/m\^2) at Visit 1 * Uncontrolled severe asthma * A chest x-ray with no abnormality * Females of childbearing potential who are sexually active with a non-sterilized male partner must use highly effective contraception from Day 1 * Non-sterilized males or sterilized males who are less than or equal to (=\<) 1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception
Exclusion criteria
* Employee of the clinical study site or any other individuals directly involved with the conduct of the study, or immediate family members of such individuals * Pregnant or breastfeeding women * Any other respiratory disease * Previously taken tralokinumab (the study drug) * Current smoker or a history of smoking which would be more than 1 pack per day for 10 years * Known immune deficiency * History of cancer * Hepatitis B, C or Human Immuno-deficiency Virus (HIV) * Any disease which may cause complications whilst taking the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate (AER) | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids (OCS) is administered (10 days after administration of an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FEV1 and FVC at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Ratio of FEV1/FVC was analysed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) | Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) | The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Baseline and Week 53 | Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline and Week 53 | AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Week 53 | The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems) that reflects increasing levels of difficulty. The minimum possible value is 5 (one point for each dimension) and the maximum possible values is 15 (3 points for each dimension). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53 | Baseline and Week 53 | The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53) | There were 3 symptom questions in the ASMA diary: daytime frequency (question 1), daytime severity (question 2) and nighttime severity (question 6). All symptom questions were scored from 0 to 4 averaged, where a higher score indicated greater frequency or severity. Daily Asthma symptom scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Rescue Medication Use at Week 53 | Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53) | Rescue medication use was collected from 3 questions: daytime use in response to symptoms (question 3), daytime prophylactic use (question 4) and nighttime use (question 7). Rescue medication use questions were first assessed using a dichotomous response option (YES/NO). If the participants reported YES, there was a subsequent question about the number of times rescue medication was used (questions 3a, 4a, and 7a). Daily average scores were summarized each week for all participants with at least 4 non-missing records each week. Days with no reported rescue medication use were represented as 0 and included in the calculation with participants who reported yes and completed questions 3a, 4a and 7a. The baseline scores were calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | Baseline and Week 75 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Week 75 that were absent before treatment or that worsened relative to pre-treatment state. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Observed Serum Tralokinumab Concentration at Week 53 | Week 53 | Tralokinumab concentrations that were below limit of quantification (LOQ) of the pharmacokinetic (PK) assay (LOQ = 0.500 microgram per milliliter \[mcg/mL\]) were replaced by LOQ/2 = 0.250 mcg/mL; results were reported to 3 significant figures level of precision. Observed serum tralokinumab concentration at Week 53 was reported. |
| Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Baseline and Week 75 | Immunogenicity assessment included determination of anti-drug (tralokinumab) antibodies in serum samples. ADA positive was defined as a titer greater than or equal to (\>=13) at any point in the study. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Severe Annual Asthma Exacerbation Rate (AER) | Week 1 up to Week 53 | Severe annualized AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids is administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Time to First Exacerbation Through Week 53 | Week 1 up to Week 53 | Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Time to First Severe Exacerbation Through Week 53 | Week 1 up to Week 53 | Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline serum periostin greater than or equal to (\>=) or less than (\<) median, \>= or \< 25th percentile and \>= or \< 75th percentile. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Th2 status. Th2-high included those participants who had immunoglobulin E (IgE) \>100 international unit per milliliter (IU/mL) and blood eosinophils \>= 0.14 \* 10 power 9 per Liter. Th2 low would include those participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroups baseline peripheral blood eosinophil counts. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup baseline FEV1 reversibility \>=12% and \<12%. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline FEV1% predicaed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup as asthma exacerbations in the past year. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | Week 1 up to Week 53 | Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER evaluated by subgroup baseline serum periostin. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Week 1 up to Week 53 | Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup FEV1 reversibility. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Week 1 up to Week 53 | Severe AER was assessed based on AER data up to Week 53. An asthma exacerbation is a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 days. It was considered resolved 7 days after last dose of OCS administered (10 days after injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup Th2 status. Th2-high include participants who had IgE \>100 IU/mL and blood eosinophils \>=0.14\*10\^9/Liter. Th2 low would include participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | Week 1 up to Week 53 | Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup baseline peripheral blood eosinophil count. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Week 1 up to Week 53 | Prebronchodilator FEV1 was evaluated by subgroups. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Week 1 up to Week 53 | Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Week 1 up to Week 53 | AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Atopic and Non-atopic asthma status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | Week 1 up to Week 53 | Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup chronic OCS use. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53) | Scores for nighttime awakenings were generated based on the single item (question 5) that had a dichotomous response option (YES/NO). Nighttime awakenings were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated with data from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Change From Baseline in Overall Activity Limitations at Week 53 | Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53) | There were 3 activity limitation questions in the ASMA diary. All activity questions were scored from 0 to 4 and averaged, where the higher score indicated greater limitation. Activity limitation scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV1 was measured in liters. |
| Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FVC was measured in liters. |
| Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for IC was measured in liters. |
| Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) | Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53) | The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. |
| Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Baseline and Week 53 | Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV6 was measured in liters. |
Countries
Argentina, Canada, Chile, Czechia, France, Germany, Japan, Mexico, Philippines, Poland, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 689 participants were screened, out of which 452 participants were randomized into this study
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Q2W - Cohort 1 Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks. | 76 |
| Tralokinumab 300 mg, Q2W - Cohort 1 Participants received tralokinumab 300 milligram (mg) subcutaneous injection every 2 weeks (Q2W) for a total of 26 doses up to 50 weeks. | 150 |
| Placebo, Q2/4W - Cohort 2 Participants received matching placebo subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses. | 75 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 Participants received tralokinumab 300 mg subcutaneous injection every 2 weeks (Q2W) for 12 weeks followed by every 4 weeks (Q4W) for 38 weeks (Q2/4W) for a total of 16 doses. | 151 |
| Total | 452 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Other | 2 | 5 | 1 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 10 | 7 | 13 |
Baseline characteristics
| Characteristic | Placebo, Q2W - Cohort 1 | Tralokinumab 300 mg, Q2W - Cohort 1 | Placebo, Q2/4W - Cohort 2 | Tralokinumab 300 mg, Q2/4W - Cohort 2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 12.1 | 49.7 years STANDARD_DEVIATION 12.2 | 51.7 years STANDARD_DEVIATION 13.6 | 50.5 years STANDARD_DEVIATION 11.8 | 50.1 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 51 Participants | 100 Participants | 46 Participants | 100 Participants | 297 Participants |
| Sex: Female, Male Male | 25 Participants | 50 Participants | 29 Participants | 51 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 128 / 151 | 133 / 150 | 128 / 151 |
| serious Total, serious adverse events | 21 / 151 | 18 / 150 | 25 / 151 |
Outcome results
Primary
Annual Asthma Exacerbation Rate (AER)
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids (OCS) is administered (10 days after administration of an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The intent-to-treat (ITT) population included all participants who were randomized into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) | 0.90 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) | 0.91 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) | 0.97 AER events/person-year |
Comparison: The 95 percent (%) confidence interval (CI) for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 versus \[vs\] more than \[\>\] 2 but less than or equal to \[=\<\] 6), atopic asthma status (atopic/non-atopic), chronic oral corticosteroid (OCS) use (presence vs absence) and geographical region as the covariates.p-value: 0.70995% CI: [0.67, 1.31]Poisson regression
Comparison: The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs \> 2 but =\< 6), atopic asthma status (atopic/non-atopic), chronic OCS use (presence vs absence) and geographical region as the covariates.p-value: 0.90495% CI: [0.71, 1.46]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup as asthma exacerbations in the past year. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | 2 asthma exacerbations (n=97,96,95) | 0.62 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | > 2 but < 6 asthma exacerbations (n=54,54,56) | 1.44 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | 2 asthma exacerbations (n=97,96,95) | 0.61 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | > 2 but < 6 asthma exacerbations (n=54,54,56) | 1.42 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | 2 asthma exacerbations (n=97,96,95) | 0.45 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Asthma Exacerbations in the Past Year | > 2 but < 6 asthma exacerbations (n=54,54,56) | 1.88 AER events/person-year |
Comparison: 2 asthma exacerbations in the past yearp-value: 0.80295% CI: [0.58, 1.52]Poisson regression
Comparison: 2 asthma exacerbations in the past yearp-value: 0.0595% CI: [0.36, 1]Poisson regression
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.79295% CI: [0.56, 1.56]Poisson regression
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.23195% CI: [0.81, 2.38]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Atopic and Non-atopic asthma status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Atopic asthma (n=96,105,92) | 0.85 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Non-atopic asthma (n=51,42,55) | 1.05 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Atopic asthma (n=96,105,92) | 0.90 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Non-atopic asthma (n=51,42,55) | 0.82 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Atopic asthma (n=96,105,92) | 0.85 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Atopic Asthma Status | Non-atopic asthma (n=51,42,55) | 1.10 AER events/person-year |
Comparison: Atopic asthmap-value: 0.80395% CI: [0.62, 1.44]Poisson regression
Comparison: Atopic asthmap-value: 0.45795% CI: [0.52, 1.35]Poisson regression
Comparison: Non-atopic asthmap-value: 0.2595% CI: [0.4, 1.27]Poisson regression
Comparison: Non-atopic asthmap-value: 0.79495% CI: [0.66, 1.74]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline FEV1% predicaed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=60% (n=49,45,56) | 1.05 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=80% (n=119,109,105) | 0.93 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=60% (n=49,45,56) | 0.95 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=80% (n=119,109,105) | 0.88 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=60% (n=49,45,56) | 1.67 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1% Predicted | FEV1% Predicted <=80% (n=119,109,105) | 1.13 AER events/person-year |
Comparison: Baseline FEV1% predicted \<=60%p-value: 0.72395% CI: [0.52, 1.56]Poisson regression
Comparison: Baseline FEV1% predicted \<=60%p-value: 0.85295% CI: [0.6, 1.86]Poisson regression
Comparison: Baseline FEV1% predicted \<=80%p-value: 0.40995% CI: [0.6, 1.23]Poisson regression
Comparison: Baseline FEV1% predicted \<=80%p-value: 0.74495% CI: [0.72, 1.58]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup baseline FEV1 reversibility \>=12% and \<12%. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 0.88 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.93 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 0.68 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.99 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 1.08 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.90 AER events/person-year |
Comparison: Baseline FEV1 reversibility \>=12%p-value: 0.24595% CI: [0.33, 1.32]Poisson regression
Comparison: Baseline FEV1 reversibility \>=12%p-value: 0.43895% CI: [0.37, 1.54]Poisson regression
Comparison: Baseline FEV1 reversibility \<12%p-value: 0.94795% CI: [0.66, 1.57]Poisson regression
Comparison: Baseline FEV1 reversibility \<12%p-value: 0.91695% CI: [0.59, 1.59]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroups baseline peripheral blood eosinophil counts. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 150 cells/mcgL (n=95,104,92) | 0.95 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 150 cells/mcgL (n=48,38,52) | 0.90 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 1.00 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.89 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.83 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 150 cells/mcgL (n=95,104,92) | 0.84 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 1.01 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 150 cells/mcgL (n=48,38,52) | 1.09 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.63 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 150 cells/mcgL (n=48,38,52) | 0.95 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 1.56 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 150 cells/mcgL (n=95,104,92) | 0.96 AER events/person-year |
Comparison: Baseline eosinophil count \>=150 cells/mcgLp-value: 0.33595% CI: [0.56, 1.22]Poisson regression
Comparison: Baseline eosinophil count \>=150 cells/mcgLp-value: 0.58695% CI: [0.54, 1.41]Poisson regression
Comparison: Baseline eosinophil count \<150 cells/mcgLp-value: 0.33195% CI: [0.73, 2.52]Poisson regression
Comparison: Baseline eosinophil count \<150 cells/mcgLp-value: 0.31195% CI: [0.73, 2.71]Poisson regression
Comparison: Baseline eosinophil count \>=300 cells/mcgLp-value: 0.41495% CI: [0.48, 1.35]Poisson regression
Comparison: Baseline eosinophil count \>=300 cells/mcgLp-value: 0.46395% CI: [0.68, 2.36]Poisson regression
Comparison: Baseline eosinophil count \<300 cells/mcgLp-value: 0.79395% CI: [0.67, 1.68]Poisson regression
Comparison: Baseline eosinophil count \<300 cells/mcgLp-value: 0.26495% CI: [0.49, 1.22]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER was evaluated by subgroup baseline serum periostin greater than or equal to (\>=) or less than (\<) median, \>= or \< 25th percentile and \>= or \< 75th percentile. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 25th Percentile (n=105,115,119) | 0.94 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 1.13 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 25th Percentile (n=46,35,31) | 0.83 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 75th Percentile (n=119,107,111) | 0.85 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.73 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 75th Percentile (n=32,43,39) | 1.13 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.98 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 0.85 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 25th Percentile (n=105,115,119) | 0.84 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 25th Percentile (n=46,35,31) | 1.14 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 75th Percentile (n=32,43,39) | 0.91 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 75th Percentile (n=119,107,111) | 0.91 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.63 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 75th Percentile (n=119,107,111) | 0.60 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 75th Percentile (n=32,43,39) | 2.03 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= 25th Percentile (n=105,115,119) | 1.05 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 1.27 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < 25th Percentile (n=46,35,31) | 0.65 AER events/person-year |
Comparison: Baseline serum periostin \>= medianp-value: 0.1995% CI: [0.46, 1.17]Poisson regression
Comparison: Baseline serum periostin \>= medianp-value: 0.85695% CI: [0.56, 1.61]Poisson regression
Comparison: Baseline serum periostin \< medianp-value: 0.60295% CI: [0.71, 1.81]Poisson regression
Comparison: Baseline serum periostin \< medianp-value: 0.70395% CI: [0.55, 1.5]Poisson regression
Comparison: Baseline serum periostin \>= 25th Percentilep-value: 0.45595% CI: [0.58, 1.28]Poisson regression
Comparison: Baseline serum periostin \>= 25th Percentilep-value: 0.92995% CI: [0.66, 1.57]Poisson regression
Comparison: Baseline serum periostin \< 25th Percentilep-value: 0.50795% CI: [0.63, 2.51]Poisson regression
Comparison: Baseline serum periostin \< 25th Percentilep-value: 0.80595% CI: [0.44, 1.89]Poisson regression
Comparison: Baseline serum periostin \>= 75th Percentilep-value: 0.71695% CI: [0.44, 1.75]Poisson regression
Comparison: Baseline serum periostin \>= 75th Percentilep-value: 0.32895% CI: [0.66, 3.43]Poisson regression
Comparison: Baseline serum periostin \< 75th Percentilep-value: 0.80495% CI: [0.64, 1.41]Poission regression
Comparison: Baseline serum periostin \< 75th Percentilep-value: 0.08895% CI: [0.47, 1.05]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. AER evaluated by subgroup chronic OCS use. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | With chronic OCS use (n=27,26,24) | 1.37 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | Without chronic OCS use (124,124,127) | 0.81 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | With chronic OCS use (n=27,26,24) | 2.04 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | Without chronic OCS use (124,124,127) | 0.68 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | With chronic OCS use (n=27,26,24) | 2.2 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by Chronic OCS Use | Without chronic OCS use (124,124,127) | 0.74 AER events/person-year |
Comparison: With chronic OCS usep-value: 0.61495% CI: [0.59, 2.46]Poisson regression
Comparison: With chronic OCS usep-value: 0.50695% CI: [0.61, 2.74]Poisson regression
Comparison: Without chronic OCS usep-value: 0.24395% CI: [0.53, 1.18]Poisson regression
Comparison: Without chronic OCS usep-value: 0.53195% CI: [0.57, 1.34]Poisson regression
Secondary
Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status
Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. AER was evaluated by subgroup Th2 status. Th2-high included those participants who had immunoglobulin E (IgE) \>100 international unit per milliliter (IU/mL) and blood eosinophils \>= 0.14 \* 10 power 9 per Liter. Th2 low would include those participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 0.96 AER events/person-year |
| Placebo Total | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.90 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 0.94 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.88 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 1.09 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Annual Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.85 AER events/person-year |
Comparison: Th2 highp-value: 0.36595% CI: [0.5, 1.29]Poisson regression
Comparison: Th2 highp-value: 0.92295% CI: [0.56, 1.68]Poisson regression
Comparison: Th2 Lowp-value: 0.68595% CI: [0.67, 1.84]Poisson regression
Comparison: Th2 Lowp-value: 0.81395% CI: [0.66, 1.7]Poisson regression
Secondary
Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53
There were 3 symptom questions in the ASMA diary: daytime frequency (question 1), daytime severity (question 2) and nighttime severity (question 6). All symptom questions were scored from 0 to 4 averaged, where a higher score indicated greater frequency or severity. Daily Asthma symptom scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.60 units on a scale | Standard Deviation 0.71 |
| Placebo Total | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.43 units on a scale | Standard Deviation 0.75 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.49 units on a scale | Standard Deviation 0.77 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.42 units on a scale | Standard Deviation 0.73 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.56 units on a scale | Standard Deviation 0.69 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Assessing Symptoms of Moderate-to-severe Asthma (ASMA) at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.49 units on a scale | Standard Deviation 0.78 |
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53
AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Overall (n=147,142,141) | 4.05 units on a scale | Standard Error 0.09 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Overall (n=107,109,101) | 0.85 units on a scale | Standard Error 0.1 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Symptoms (n=147,142,141) | 4.10 units on a scale | Standard Error 0.09 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Symptoms (n=107,109,101) | 0.85 units on a scale | Standard Error 0.11 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Activity limitation (n=147,142,141) | 4.04 units on a scale | Standard Error 0.08 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Activity limitation (n=107,109,101) | 0.81 units on a scale | Standard Error 0.1 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Emotional Function (n=147,142,141) | 4.14 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Emotional Function (n=107,109,101) | 0.89 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Environmental stimuli (n=147,142,141) | 3.80 units on a scale | Standard Error 0.11 |
| Placebo Total | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Environmental stimuli (n=107,109,101) | 0.88 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Environmental stimuli (n=147,142,141) | 3.76 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Overall (n=147,142,141) | 3.98 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Activity limitation (n=107,109,101) | 0.96 units on a scale | Standard Error 0.1 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Activity limitation (n=147,142,141) | 4.04 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Overall (n=107,109,101) | 1.04 units on a scale | Standard Error 0.1 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Environmental stimuli (n=107,109,101) | 0.86 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Emotional Function (n=107,109,101) | 1.10 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Symptoms (n=147,142,141) | 4.03 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Emotional Function (n=147,142,141) | 3.91 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Symptoms (n=107,109,101) | 1.14 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Emotional Function (n=107,109,101) | 1.09 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Symptoms (n=107,109,101) | 1.05 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Activity limitation (n=147,142,141) | 4.13 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Activity limitation (n=107,109,101) | 0.93 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Environmental stimuli (n=147,142,141) | 3.89 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Emotional Function (n=147,142,141) | 4.02 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Overall (n=147,142,141) | 4.08 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Environmental stimuli (n=107,109,101) | 0.97 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Week 53: Overall (n=107,109,101) | 1.00 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Asthma Quality of Life Questionnaire Standardized Version (AQLQ[S]) Score at Week 53 | Baseline: Symptoms (n=147,142,141) | 4.13 units on a scale | Standard Error 0.09 |
Secondary
Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Total | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53 | 8.4 units on a scale | Standard Error 1.6 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53 | 9.3 units on a scale | Standard Error 1.9 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Week 53 | 7.3 units on a scale | Standard Error 1.8 |
Secondary
Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 25, 34, 27) | -0.75 units on a scale | Standard Error 0.14 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < Median (n= 67, 50, 52) | -0.77 units on a scale | Standard Error 0.14 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 82, 92, 91) | -0.86 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 36, 23, 21) | -0.73 units on a scale | Standard Error 0.19 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 51, 65, 60) | -0.88 units on a scale | Standard Error 0.15 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 93, 81, 85) | -0.84 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 High (n= 59, 56, 55) | -0.95 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 Low (n= 55, 47, 50) | -0.70 units on a scale | Standard Error 0.16 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n= 77, 78, 70) | -0.84 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 150 Cells/UL (n= 37, 31, 37) | -0.81 units on a scale | Standard Error 0.18 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 43, 44, 37) | -0.77 units on a scale | Standard Error 0.15 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (n= 71, 65, 70) | -0.86 units on a scale | Standard Error 0.14 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 43, 33, 35) | -0.47 units on a scale | Standard Error 0.19 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 73, 78, 75) | -1.03 units on a scale | Standard Error 0.11 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n= 79, 72, 75) | -0.77 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 39, 43, 37) | -0.93 units on a scale | Standard Error 0.17 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 20, 17, 18) | -0.39 units on a scale | Standard Error 0.25 |
| Placebo Total | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 98, 98, 94) | -0.91 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 98, 98, 94) | -1.04 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 51, 65, 60) | -1.18 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 150 Cells/UL (n= 37, 31, 37) | -0.92 units on a scale | Standard Error 0.16 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 43, 33, 35) | -0.90 units on a scale | Standard Error 0.18 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < Median (n= 67, 50, 52) | -0.81 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n= 79, 72, 75) | -0.94 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 39, 43, 37) | -1.15 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 82, 92, 91) | -1.04 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 43, 44, 37) | -1.24 units on a scale | Standard Error 0.16 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 20, 17, 18) | -0.89 units on a scale | Standard Error 0.28 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 36, 23, 21) | -0.95 units on a scale | Standard Error 0.24 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n= 77, 78, 70) | -1.07 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 73, 78, 75) | -1.12 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 25, 34, 27) | -1.25 units on a scale | Standard Error 0.18 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 Low (n= 55, 47, 50) | -0.94 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (n= 71, 65, 70) | -0.88 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 93, 81, 85) | -0.92 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 High (n= 59, 56, 55) | -1.10 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 93, 81, 85) | -0.91 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 High (n= 59, 56, 55) | -1.02 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Th2 Low (n= 55, 47, 50) | -0.87 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n= 79, 72, 75) | -0.95 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n= 77, 78, 70) | -0.94 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 98, 98, 94) | -1.08 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 150 Cells/UL (n= 37, 31, 37) | -1.02 units on a scale | Standard Error 0.21 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 43, 44, 37) | -0.91 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 39, 43, 37) | -0.90 units on a scale | Standard Error 0.19 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (n= 71, 65, 70) | -1.00 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 51, 65, 60) | -0.85 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < Median (n= 67, 50, 52) | -1.03 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 43, 33, 35) | -0.76 units on a scale | Standard Error 0.2 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 82, 92, 91) | -0.93 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 36, 23, 21) | -0.92 units on a scale | Standard Error 0.24 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 25, 34, 27) | -1.01 units on a scale | Standard Error 0.23 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 73, 78, 75) | -1.02 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean ACQ-6 Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 20, 17, 18) | -0.16 units on a scale | Standard Error 0.23 |
Comparison: Baseline serum periostin \>= medianp-value: 0.14595% CI: [-0.57, 0.08]Repeated measure model
Comparison: Baseline serum periostin \>= medianp-value: 0.75995% CI: [-0.28, 0.38]Repeated measure model
Comparison: Baseline serum periostin \< medianp-value: 0.93695% CI: [-0.38, 0.35]Repeated measure model
Comparison: Baseline serum periostin \< medianp-value: 0.12795% CI: [-0.64, 0.08]Repeated measure model
Comparison: Baseline serum periostin\>= 25th percentilep-value: 0.34395% CI: [-0.41, 0.14]Repeated measure model
Comparison: Baseline serum periostin\>= 25th percentilep-value: 0.92895% CI: [-0.29, 0.27]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.37495% CI: [-0.74, 0.28]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.25995% CI: [-0.81, 0.22]Repeated measure model
Comparison: Baseline serum periostin \>= 75th percentilep-value: 0.12795% CI: [-0.84, 0.11]Repeated measure model
Comparison: Baseline serum periostin \>= 75th percentilep-value: 0.77595% CI: [-0.56, 0.42]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.51295% CI: [-0.38, 0.19]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.40495% CI: [-0.4, 0.16]Repeated measure model
Comparison: Th2 highp-value: 0.18195% CI: [-0.59, 0.11]Repeated measure model
Comparison: Th2 highp-value: 0.16195% CI: [-0.6, 0.1]Repeated measure model
Comparison: Th2 lowp-value: 0.5495% CI: [-0.47, 0.25]Repeated measure model
Comparison: Th2 lowp-value: 0.67495% CI: [-0.42, 0.27]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 150 cells/μLp-value: 0.15495% CI: [-0.52, 0.08]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 150 cells/μp-value: 0.27195% CI: [-0.48, 0.13]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.72595% CI: [-0.51, 0.36]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.55995% CI: [-0.53, 0.28]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.01995% CI: [-0.87, -0.08]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.34895% CI: [-0.61, 0.21]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μLp-value: 0.85595% CI: [-0.35, 0.29]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μLp-value: 0.20395% CI: [-0.5, 0.11]Repeated measure model
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.05595% CI: [-0.89, 0.01]Repeated measure model
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.10495% CI: [-0.82, 0.08]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.65295% CI: [-0.37, 0.23]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.90595% CI: [-0.28, 0.32]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.19895% CI: [-0.49, 0.1]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.22695% CI: [-0.47, 0.11]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.51395% CI: [-0.56, 0.28]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.97495% CI: [-0.43, 0.42]Repeated measure model
Comparison: Chronic OCS usep-value: 0.22695% CI: [-0.97, 0.23]Repeated measure model
Comparison: Chronic OCS usep-value: 0.61395% CI: [-0.44, 0.75]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.19895% CI: [-0.43, 0.09]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.16595% CI: [-0.45, 0.08]Repeated measure model
Secondary
Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Baseline (n=149,147,148) | 2.52 units on a scale | Standard Error 0.07 |
| Placebo Total | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Change at Week 53 (n=118,115,112) | -0.82 units on a scale | Standard Error 0.1 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Baseline (n=149,147,148) | 2.59 units on a scale | Standard Error 0.09 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Change at Week 53 (n=118,115,112) | -1.02 units on a scale | Standard Error 0.1 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Baseline (n=149,147,148) | 2.54 units on a scale | Standard Error 0.08 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Mean Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 53 | Change at Week 53 (n=118,115,112) | -0.93 units on a scale | Standard Error 0.11 |
Secondary
Change From Baseline in Overall Activity Limitations at Week 53
There were 3 activity limitation questions in the ASMA diary. All activity questions were scored from 0 to 4 and averaged, where the higher score indicated greater limitation. Activity limitation scores were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Overall Activity Limitations at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.71 units on a scale | Standard Deviation 0.86 |
| Placebo Total | Change From Baseline in Overall Activity Limitations at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.45 units on a scale | Standard Deviation 0.81 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Overall Activity Limitations at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.52 units on a scale | Standard Deviation 0.9 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Overall Activity Limitations at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.38 units on a scale | Standard Deviation 0.84 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Overall Activity Limitations at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 1.63 units on a scale | Standard Deviation 0.85 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Overall Activity Limitations at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.48 units on a scale | Standard Deviation 0.87 |
Secondary
Change From Baseline in Percentage of Nighttime Awakening at Week 53
Scores for nighttime awakenings were generated based on the single item (question 5) that had a dichotomous response option (YES/NO). Nighttime awakenings were averaged weekly for participants with at least 4 non-missing records each week. The baseline score was calculated with data from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 0.44 percentage change | Standard Deviation 0.42 |
| Placebo Total | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.22 percentage change | Standard Deviation 0.43 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 0.42 percentage change | Standard Deviation 0.43 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.18 percentage change | Standard Deviation 0.37 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 0.43 percentage change | Standard Deviation 0.43 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Percentage of Nighttime Awakening at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.23 percentage change | Standard Deviation 0.45 |
Secondary
Change From Baseline in Rescue Medication Use at Week 53
Rescue medication use was collected from 3 questions: daytime use in response to symptoms (question 3), daytime prophylactic use (question 4) and nighttime use (question 7). Rescue medication use questions were first assessed using a dichotomous response option (YES/NO). If the participants reported YES, there was a subsequent question about the number of times rescue medication was used (questions 3a, 4a, and 7a). Daily average scores were summarized each week for all participants with at least 4 non-missing records each week. Days with no reported rescue medication use were represented as 0 and included in the calculation with participants who reported yes and completed questions 3a, 4a and 7a. The baseline scores were calculated from Day -7 to Day -1. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day -7 - Day -1 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Rescue Medication Use at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 2.56 use per day | Standard Deviation 2.73 |
| Placebo Total | Change From Baseline in Rescue Medication Use at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.86 use per day | Standard Deviation 2.2 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Rescue Medication Use at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 2.77 use per day | Standard Deviation 3.78 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Rescue Medication Use at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -0.77 use per day | Standard Deviation 2.59 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Rescue Medication Use at Week 53 | Day -7 - Day -1 (Baseline) (n=151,147,145) | 2.38 use per day | Standard Deviation 2.58 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Rescue Medication Use at Week 53 | Change at Day 365 - Day 371 (n=113,108,108) | -1.02 use per day | Standard Deviation 2.3 |
Secondary
Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups
AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (N= 64, 63, 61) | 0.84 units on a scale | Standard Error 0.14 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 34, 21, 19) | 0.81 units on a scale | Standard Error 0.19 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 90, 93, 85) | 0.91 units on a scale | Standard Error 0.11 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n=69, 72, 64) | 0.91 units on a scale | Standard Error 0.11 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 73, 88, 82) | 0.87 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < Median ( n= 61, 46, 45) | 0.82 units on a scale | Standard Error 0.14 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 low (n= 49, 45, 44 ) | 0.79 units on a scale | Standard Error 0.17 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 46, 63, 56) | 0.89 units on a scale | Standard Error 0.15 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 66, 76, 67) | 0.94 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 39, 40, 35) | 0.81 units on a scale | Standard Error 0.15 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 high (n=54,52,50) | 0.88 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n=73, 68, 68) | 0.88 units on a scale | Standard Error 0.13 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC< 150 Cells/UL (n= 34, 31, 32) | 0.68 units on a scale | Standard Error 0.2 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 84, 76, 77) | 0.87 units on a scale | Standard Error 0.12 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 34, 41, 33) | 0.78 units on a scale | Standard Error 0.16 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 39, 29, 32) | 0.75 units on a scale | Standard Error 0.17 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 23, 33, 24) | 0.76 units on a scale | Standard Error 0.17 |
| Placebo Total | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 17, 16, 16) | 0.53 units on a scale | Standard Error 0.19 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n=73, 68, 68) | 1.09 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (N= 64, 63, 61) | 1.05 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 39, 29, 32) | 1.14 units on a scale | Standard Error 0.16 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 66, 76, 67) | 1.04 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 39, 40, 35) | 0.98 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 34, 41, 33) | 0.96 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 17, 16, 16) | 0.87 units on a scale | Standard Error 0.29 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 90, 93, 85) | 1.07 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 46, 63, 56) | 1.10 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < Median ( n= 61, 46, 45) | 0.95 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 73, 88, 82) | 1.08 units on a scale | Standard Error 0.11 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 34, 21, 19) | 0.84 units on a scale | Standard Error 0.24 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 23, 33, 24) | 1.20 units on a scale | Standard Error 0.19 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 84, 76, 77) | 0.97 units on a scale | Standard Error 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 high (n=54,52,50) | 1.12 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 low (n= 49, 45, 44 ) | 0.88 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n=69, 72, 64) | 1.06 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC< 150 Cells/UL (n= 34, 31, 32) | 0.93 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 25th Percentile (n= 34, 21, 19) | 1.09 units on a scale | Standard Error 0.24 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | >2 Asthma Exacerbations (n= 34, 41, 33) | 0.73 units on a scale | Standard Error 0.2 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC< 150 Cells/UL (n= 34, 31, 32) | 1.05 units on a scale | Standard Error 0.2 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 75th Percentile (n= 23, 33, 24) | 1.13 units on a scale | Standard Error 0.28 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | 2 Asthma Exacerbations (n=73, 68, 68) | 1.14 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 150 Cells/UL (n=69, 72, 64) | 1.02 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < 75th Percentile (n= 84, 76, 77) | 0.96 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility < 12% (n= 66, 76, 67) | 1.04 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC < 300 Cells/UL (N= 64, 63, 61) | 1.15 units on a scale | Standard Error 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= Median (n= 46, 63, 56) | 0.95 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 high (n=54,52,50) | 1.12 units on a scale | Standard Error 0.18 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline EC >= 300 Cells/UL (n= 39, 40, 35) | 0.82 units on a scale | Standard Error 0.2 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP < Median ( n= 61, 46, 45) | 1.07 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Without Chronic OCS Use (n= 90, 93, 85) | 1.14 units on a scale | Standard Error 0.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Th2 low (n= 49, 45, 44 ) | 0.94 units on a scale | Standard Error 0.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline SP >= 25th Percentile (n= 73, 88, 82) | 0.98 units on a scale | Standard Error 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | With Chronic OCS Use (n= 17, 16, 16) | 0.26 units on a scale | Standard Error 0.26 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Change From Baseline in Total AQLQ(S) Scores at Week 53 in Subgroups | Baseline FEV1 Reversibility >= 12% (n= 39, 29, 32) | 0.95 units on a scale | Standard Error 0.22 |
Comparison: Baseline serum periostin \>= medianp-value: 0.21195% CI: [-0.13, 0.6]Repeated measure model
Comparison: Baseline serum periostin \>= medianp-value: 0.39795% CI: [-0.21, 0.53]Repeated measure model
Comparison: Baseline serum periostin \< medianp-value: 0.31595% CI: [-0.18, 0.56]Repeated Measure Model
Comparison: Baseline serum periostin \< medianp-value: 0.16695% CI: [-0.11, 0.63]Repeated measure model
Comparison: Baseline serum periostin \>= 25th percentilep-value: 0.26295% CI: [-0.13, 0.47]Repeated measure model
Comparison: Baseline serum periostin \>= 25th percentilep-value: 0.37995% CI: [-0.17, 0.44]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.38795% CI: [-0.32, 0.81]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.30395% CI: [-0.26, 0.84]Repeated measure model
Comparison: Baseline serum periostin \>=75th percentilep-value: 0.12795% CI: [-0.84, 0.11]Repeated measure model
Comparison: Baseline serum periostin \>=75th percentilep-value: 0.77595% CI: [-0.56, 0.42]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.51295% CI: [-0.38, 0.19]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.40495% CI: [-0.4, 0.16]Repeated measure model
Comparison: Th2 highp-value: 0.10295% CI: [-0.06, 0.69]Repeated measure model
Comparison: Th2 highp-value: 0.11695% CI: [-0.08, 0.68]Repeated measure model
Comparison: Th2 lowp-value: 0.5495% CI: [-0.47, 0.25]Repeated measure model
Comparison: Th2 lowp-value: 0.67495% CI: [-0.42, 0.27]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>=150 cells/μLp-value: 0.29595% CI: [-0.15, 0.49]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>=150 cells/μLp-value: 0.34295% CI: [-0.17, 0.49]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.40695% CI: [-0.24, 0.6]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.06995% CI: [-0.03, 0.79]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.37195% CI: [-0.23, 0.62]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.76695% CI: [-0.37, 0.51]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μLp-value: 0.14795% CI: [-0.09, 0.57]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μLp-value: 0.03195% CI: [0.03, 0.68]Repeated measure model
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.0295% CI: [0.1, 1.09]Repeated measure model
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.22695% CI: [-0.18, 0.77]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.96495% CI: [-0.31, 0.33]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.53395% CI: [-0.22, 0.42]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.29295% CI: [-0.15, 0.5]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.09795% CI: [-0.05, 0.59]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.2695% CI: [-0.18, 0.67]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.64895% CI: [-0.33, 0.53]Repeated measure model
Comparison: Chronic OCS usep-value: 0.39895% CI: [-0.37, 0.93]Repeated measure model
Comparison: Chronic OCS usep-value: 0.32795% CI: [-0.95, 0.32]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.10595% CI: [-0.05, 0.52]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.0395% CI: [0.03, 0.6]Repeated measure model
Secondary
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53
Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 1.926 liters | Standard Error 0.05 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 2.153 liters | Standard Error 0.053 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.018 liters | Standard Error 0.035 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.058 liters | Standard Error 0.027 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | 0.085 liters | Standard Error 0.029 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 1.922 liters | Standard Error 0.056 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.128 liters | Standard Error 0.032 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 2.094 liters | Standard Error 0.061 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.009 liters | Standard Error 0.025 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 2.110 liters | Standard Error 0.061 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.032 liters | Standard Error 0.026 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 1.934 liters | Standard Error 0.059 |
Secondary
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home
Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 1.63 liters | Standard Error 0.05 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | -0.12 liters | Standard Error 0.06 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 1.61 liters | Standard Error 0.05 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -0.08 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -0.08 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 1.61 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 1.68 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | 0.01 liters | Standard Error 0.04 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -0.12 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | -0.07 liters | Standard Error 0.06 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 1.65 liters | Standard Error 0.05 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 1.66 liters | Standard Error 0.05 |
Secondary
Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53
Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 2.830 liters | Standard Error 0.064 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 3.055 liters | Standard Error 0.067 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.007 liters | Standard Error 0.036 |
| Placebo Total | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.057 liters | Standard Error 0.03 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | 0.060 liters | Standard Error 0.033 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 2.809 liters | Standard Error 0.072 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.117 liters | Standard Error 0.037 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 2.981 liters | Standard Error 0.075 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.024 liters | Standard Error 0.029 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 2.980 liters | Standard Error 0.076 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.003 liters | Standard Error 0.031 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 2.827 liters | Standard Error 0.074 |
Secondary
Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53
Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 3.003 liters | Standard Error 0.069 |
| Placebo Total | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 3.225 liters | Standard Error 0.072 |
| Placebo Total | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | -0.001 liters | Standard Error 0.039 |
| Placebo Total | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.071 liters | Standard Error 0.032 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | 0.045 liters | Standard Error 0.034 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 2.955 liters | Standard Error 0.075 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.110 liters | Standard Error 0.042 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 3.133 liters | Standard Error 0.078 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.030 liters | Standard Error 0.031 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 3.125 liters | Standard Error 0.08 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | -0.018 liters | Standard Error 0.032 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 2.993 liters | Standard Error 0.079 |
Secondary
Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53
Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Week 53 (n=108,109,104) | 0.000 liters | Standard Error 0.001 |
| Placebo Total | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Baseline (n=140,138,143) | 0.022 liters | Standard Error 0.001 |
| Placebo Total | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Week 53 (n=108,109,103) | 0.001 liters | Standard Error 0.001 |
| Placebo Total | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Baseline (n=140,133,135) | 0.024 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Week 53 (n=108,109,103) | 0.000 liters | Standard Error 0 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Week 53 (n=108,109,104) | 0.001 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Baseline (n=140,133,135) | 0.024 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Baseline (n=140,138,143) | 0.023 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Week 53 (n=108,109,104) | 0.000 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-bronchodilator: Baseline (n=140,133,135) | 0.024 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Week 53 (n=108,109,103) | 0.001 liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator: Baseline (n=140,138,143) | 0.023 liters | Standard Error 0.001 |
Secondary
Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 273.7 liters per minute | Standard Error 8.7 |
| Placebo Total | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | -23.1 liters per minute | Standard Error 8.8 |
| Placebo Total | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 276.0 liters per minute | Standard Error 8.9 |
| Placebo Total | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -16.4 liters per minute | Standard Error 8.7 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -27.0 liters per minute | Standard Error 8.2 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 271.0 liters per minute | Standard Error 9.7 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 287.6 liters per minute | Standard Error 9.9 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | -8.0 liters per minute | Standard Error 7.9 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=120,116,112) | -36.5 liters per minute | Standard Error 8.8 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=124,119,114) | -24.0 liters per minute | Standard Error 9.6 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Evening (n=149,147,148) | 283.8 liters per minute | Standard Error 10 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Day 1-7: Morning (n=151,149,149) | 281.2 liters per minute | Standard Error 9.9 |
Secondary
Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53
Pre- and post-bronchodilator FEV1 and FVC at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Ratio of FEV1/FVC was analysed. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 64.508 percentage of ratio | Standard Error 0.986 |
| Placebo Total | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 67.152 percentage of ratio | Standard Error 0.997 |
| Placebo Total | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 0.320 percentage of ratio | Standard Error 0.685 |
| Placebo Total | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | -0.512 percentage of ratio | Standard Error 0.513 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | 1.593 percentage of ratio | Standard Error 0.563 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 65.071 percentage of ratio | Standard Error 1.013 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 1.695 percentage of ratio | Standard Error 0.517 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 66.831 percentage of ratio | Standard Error 1.056 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Week 53 (n=125,126,120) | 0.032 percentage of ratio | Standard Error 0.484 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Post-bronchodilator: Baseline (n=147,141,146) | 67.883 percentage of ratio | Standard Error 1.01 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Week 53 (n=125,130,122) | 1.155 percentage of ratio | Standard Error 0.527 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Mean Change From Baseline in Ratio of Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator: Baseline (n=147,146,146) | 65.008 percentage of ratio | Standard Error 1.009 |
Secondary
Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems) that reflects increasing levels of difficulty. The minimum possible value is 5 (one point for each dimension) and the maximum possible values is 15 (3 points for each dimension). Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 53
Population: The ITT population included all participants who were randomized into the study.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Severe problem | 4 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Missing | 17 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - No problem | 107 participants | 0.1 |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Moderate problem | 46 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - No Problem | 89 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Missing | 17 participants | 0.13 |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - No problem | 84 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Moderate Problem | 43 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Missing | 17 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Missing | 17 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Severe Problem | 2 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Moderate problem | 29 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - No Problem | 122 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Severe problem | 3 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - No problem | 102 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Moderate Problem | 12 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Severe Problem | 1 participants | 0.12 |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Missing | 17 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Severe Problem | 0 participants | — |
| Placebo Total | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Moderate problem | 26 participants | 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Moderate problem | 34 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - No problem | 118 participants | 0.1 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Moderate problem | 18 participants | 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Severe Problem | 0 participants | 0.12 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Missing | 14 participants | 0.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - No Problem | 127 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Moderate Problem | 9 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Severe Problem | 0 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Missing | 14 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - No Problem | 106 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Moderate Problem | 30 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Severe Problem | 0 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Missing | 14 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - No problem | 100 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Moderate problem | 34 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Severe problem | 2 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Missing | 14 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - No problem | 101 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Severe problem | 1 participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Missing | 14 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Moderate problem | 23 participants | 0.11 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Moderate problem | 51 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Severe Problem | 1 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Missing | 21 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Severe problem | 2 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Moderate Problem | 7 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Severe problem | 0 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - Missing | 21 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - No Problem | 122 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - No problem | 106 participants | 0.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - No problem | 101 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Missing | 21 participants | 0.14 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Severe Problem | 0 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Moderate Problem | 30 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Mobility - Severe Problem | 1 participants | 0.15 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - Missing | 21 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Usual activities - No Problem | 100 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Anxiety/depression - Moderate problem | 29 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Pain/discomfort - No problem | 77 participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With European Quality of Life 5 Dimensions (EQ-5D) Scores at Week 53 | Self-care - Missing | 21 participants | — |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Week 75 that were absent before treatment or that worsened relative to pre-treatment state. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 75
Population: The safety population included all participants who received any investigational product and had safety data available for analysis.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TEAEs | 129 participants | 17.12 |
| Placebo Total | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TESAEs | 21 participants | 1.6 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TEAEs | 134 participants | 19.83 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TESAEs | 18 participants | 1.9 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TEAEs | 128 participants | 16.98 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TESAEs | 25 participants | 1.8 |
Secondary
Observed Serum Tralokinumab Concentration at Week 53
Tralokinumab concentrations that were below limit of quantification (LOQ) of the pharmacokinetic (PK) assay (LOQ = 0.500 microgram per milliliter \[mcg/mL\]) were replaced by LOQ/2 = 0.250 mcg/mL; results were reported to 3 significant figures level of precision. Observed serum tralokinumab concentration at Week 53 was reported.
Time frame: Week 53
Population: The PK population included all participants who received at least one dose of tralokinumab and had at least one quantifiable PK observation. Here N signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Total | Observed Serum Tralokinumab Concentration at Week 53 | 71.3 microgram per milliliter | Standard Deviation 34.2 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Observed Serum Tralokinumab Concentration at Week 53 | 25.8 microgram per milliliter | Standard Deviation 11.8 |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab
Immunogenicity assessment included determination of anti-drug (tralokinumab) antibodies in serum samples. ADA positive was defined as a titer greater than or equal to (\>=13) at any point in the study. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Baseline and Week 75
Population: The PK population included all participants who received at least one dose of tralokinumab and had at least one quantifiable PK observation. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Baseline (Week 1) (n=151,150,151) | 1.3 percentage of participants | 17.12 |
| Placebo Total | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Week 75 (n=151,150,150) | 3.3 percentage of participants | — |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Baseline (Week 1) (n=151,150,151) | 0.67 percentage of participants | 19.83 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Week 75 (n=151,150,150) | 0.0 percentage of participants | — |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Baseline (Week 1) (n=151,150,151) | 1.3 percentage of participants | 16.98 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percentage of Participants With Anti-Drug Antibodies (ADA) to Tralokinumab | Week 75 (n=151,150,150) | 4.0 percentage of participants | — |
Secondary
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53
Pre- and post-bronchodilator FEV1 at clinic visits (morning) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV1 was measured in liters.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 1.926 percentage change in liters | Standard Error 0.05 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD: Baseline (n=147,141,146) | 2.153 percentage change in liters | Standard Error 0.053 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 2.50 percentage change in liters | Standard Error 1.99 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | -1.65 percentage change in liters | Standard Error 1.39 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | 5.98 percentage change in liters | Standard Error 1.85 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 1.922 percentage change in liters | Standard Error 0.056 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 9.11 percentage change in liters | Standard Error 2.13 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD: Baseline (n=147,141,146) | 2.094 percentage change in liters | Standard Error 0.061 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | 0.18 percentage change in liters | Standard Error 1.25 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Post-BD: Baseline (n=147,141,146) | 2.110 percentage change in liters | Standard Error 0.061 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 2.94 percentage change in liters | Standard Error 1.54 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 1.934 percentage change in liters | Standard Error 0.059 |
Secondary
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home
Pre- and post-bronchodilator FEV1 at home (morning and evening) were measured. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | -4.96 percentage change | Standard Error 3.27 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=119,116,111) | -2.83 percentage change | Standard Error 3.01 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | 1.67 percentage change | Standard Error 2.83 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=119,116,111) | -2.69 percentage change | Standard Error 3.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | 1.70 percentage change | Standard Error 5.41 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 53 at Home | Change at Day 365-371: Evening (n=119,116,111) | -5.78 percentage change | Standard Error 3.63 |
Secondary
Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53
Pre- and post-bronchodilator FEV6 at clinic visits (morning) were measured. FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FEV6 was measured in liters.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 2.830 percentage change in liters | Standard Error 0.064 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD: Baseline (n=147,141,146) | 3.055 percentage change in liters | Standard Error 0.067 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 1.06 percentage change in liters | Standard Error 1.29 |
| Placebo Total | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | -1.16 percentage change in liters | Standard Error 1.04 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | 3.27 percentage change in liters | Standard Error 1.36 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 2.809 percentage change in liters | Standard Error 0.072 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 5.75 percentage change in liters | Standard Error 1.53 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD: Baseline (n=147,141,146) | 2.981 percentage change in liters | Standard Error 0.075 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | -0.11 percentage change in liters | Standard Error 1.01 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Post-BD: Baseline (n=147,141,146) | 2.980 percentage change in liters | Standard Error 0.076 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 1.10 percentage change in liters | Standard Error 1.18 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Expiratory Volume in 6 Second (FEV6) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 2.827 percentage change in liters | Standard Error 0.074 |
Secondary
Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53
Pre- and post-bronchodilator FVC at clinic visits (morning) were measured. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for FVC was measured in liters.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 3.003 percentage change in liters | Standard Error 0.069 |
| Placebo Total | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD: Baseline (n=147,141,146) | 3.225 percentage change in liters | Standard Error 0.072 |
| Placebo Total | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 0.87 percentage change in liters | Standard Error 1.31 |
| Placebo Total | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | -1.51 percentage change in liters | Standard Error 1.01 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | 2.56 percentage change in liters | Standard Error 1.27 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 2.955 percentage change in liters | Standard Error 0.075 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 5.43 percentage change in liters | Standard Error 1.6 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD: Baseline (n=147,141,146) | 3.133 percentage change in liters | Standard Error 0.078 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD:Change from baseline to W53(n=125,126,120) | -0.26 percentage change in liters | Standard Error 1.03 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Post-BD: Baseline (n=147,141,146) | 3.125 percentage change in liters | Standard Error 0.08 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-BD:Change from baseline to W53 (n=125,130,122) | 0.46 percentage change in liters | Standard Error 1.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Forced Vital Capacity (FVC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=147,146,146) | 2.993 percentage change in liters | Standard Error 0.079 |
Secondary
Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53
Pre- and post-bronchodilator IC at clinic visits (morning) were measured. IC was measured by spirometry. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms. Baseline for IC was measured in liters.
Time frame: Baseline and Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=140,138,143) | 0.022 percentage change in liters | Standard Error 0.001 |
| Placebo Total | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD: Baseline (n=140,133,135) | 0.024 percentage change in liters | Standard Error 0.001 |
| Placebo Total | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-BD:Change from baseline to W53 (n=108,109,103) | 8.56 percentage change in liters | Standard Error 3.42 |
| Placebo Total | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD:Change from baseline to W53(n=108,109,104) | 3.64 percentage change in liters | Standard Error 3.17 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD:Change from baseline to W53(n=108,109,104) | 8.33 percentage change in liters | Standard Error 3.14 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=140,138,143) | 0.023 percentage change in liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-BD:Change from baseline to W53 (n=108,109,103) | 0.15 percentage change in liters | Standard Error 2.21 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD: Baseline (n=140,133,135) | 0.024 percentage change in liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD:Change from baseline to W53(n=108,109,104) | 3.17 percentage change in liters | Standard Error 2.91 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Post-BD: Baseline (n=140,133,135) | 0.024 percentage change in liters | Standard Error 0.001 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-BD:Change from baseline to W53 (n=108,109,103) | 11.38 percentage change in liters | Standard Error 3.71 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Inspiratory Capacity (IC) at Week 53 | Pre-bronchodilator(BD): Baseline (n=140,138,143) | 0.023 percentage change in liters | Standard Error 0.001 |
Secondary
Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed at home (morning and evening) while sitting or standing prior to using any medication (if needed) for asthma. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Day 1 - Day 7 (Baseline) and Day 365 - Day 371 (Week 53)
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | -6.89 percentage change | Standard Error 3.09 |
| Placebo Total | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=129,116,111) | -4.95 percentage change | Standard Error 2.99 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | -0.64 percentage change | Standard Error 3.26 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=129,116,111) | -6.62 percentage change | Standard Error 3.13 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Evening (n=129,116,111) | -11.45 percentage change | Standard Error 3.33 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Peak Expiratory Flow (PEF) at Week 53 at Home | Change at Day 365-371: Morning (n=123,119,113) | -2.80 percentage change | Standard Error 5.41 |
Secondary
Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups
Prebronchodilator FEV1 was evaluated by subgroups. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | > 2 but < 6 asthma exacerbations (n=41,49,40) | 6.08 Percent change | Standard Error 4.12 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 high (n=63,62,57) | 2.10 Percent change | Standard Error 2.62 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=75th Percentile (n=25,40,32) | 2.32 Percent change | Standard Error 4.07 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=25th Percentile (n=88,102,100) | 4.10 Percent change | Standard Error 2.29 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 low (n=57,55,55) | 1.90 Percent change | Standard Error 3.09 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <75th Percentile (n=100,90,89) | 2.55 Percent change | Standard Error 2.28 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Chronic OCS use (n=20,21,16) | 3.44 Percent change | Standard Error 5.82 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=150 cells/mcgL (n=81,89,75) | 1.98 Percent change | Standard Error 2.32 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | 2 asthma exacerbations (n=84,81,82) | 0.76 Percent change | Standard Error 2.16 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=median (n=54,71,65) | 4.17 Percent change | Standard Error 2.75 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <150 cells/mcgL (n=39,34,40) | 2.05 Percent change | Standard Error 3.89 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Without chronic OCS use (n=105,109,106) | 2.32 Percent change | Standard Error 2.1 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <25th Percentile (n=37,28,21) | -1.29 Percent change | Standard Error 3.92 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=300 cells/mcgL (n=45,51,39) | 0.59 Percent change | Standard Error 2.88 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility <12% (n=76,92,80) | -2.99 Percent change | Standard Error 1.9 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility >=12% (n=49,36,41) | 11.02 Percent change | Standard Error 3.85 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <300 cells/mcgL (n=75,72,76) | 2.85 Percent change | Standard Error 2.71 |
| Placebo Total | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <median (n=71,59,56) | 1.23 Percent change | Standard Error 2.82 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <300 cells/mcgL (n=75,72,76) | 6.33 Percent change | Standard Error 2.57 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility >=12% (n=49,36,41) | 22.78 Percent change | Standard Error 5.2 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility <12% (n=76,92,80) | 3.98 Percent change | Standard Error 1.97 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=75th Percentile (n=25,40,32) | 11.05 Percent change | Standard Error 4.67 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | 2 asthma exacerbations (n=84,81,82) | 8.99 Percent change | Standard Error 2.41 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <median (n=71,59,56) | 7.46 Percent change | Standard Error 3 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | > 2 but < 6 asthma exacerbations (n=41,49,40) | 9.32 Percent change | Standard Error 4.05 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Chronic OCS use (n=20,21,16) | 6.96 Percent change | Standard Error 6.56 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Without chronic OCS use (n=105,109,106) | 9.52 Percent change | Standard Error 2.22 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <75th Percentile (n=100,90,89) | 8.25 Percent change | Standard Error 2.29 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=median (n=54,71,65) | 10.48 Percent change | Standard Error 3.01 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 high (n=63,62,57) | 11.62 Percent change | Standard Error 3.23 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 low (n=57,55,55) | 3.87 Percent change | Standard Error 2.5 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=25th Percentile (n=88,102,100) | 10.40 Percent change | Standard Error 2.43 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=150 cells/mcgL (n=81,89,75) | 10.97 Percent change | Standard Error 2.71 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <150 cells/mcgL (n=39,34,40) | 5.75 Percent change | Standard Error 3.75 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=300 cells/mcgL (n=45,51,39) | 14.04 Percent change | Standard Error 3.88 |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <25th Percentile (n=37,28,21) | 4.40 Percent change | Standard Error 4.39 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=300 cells/mcgL (n=45,51,39) | 4.65 Percent change | Standard Error 2.9 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=median (n=54,71,65) | 4.36 Percent change | Standard Error 2.25 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <median (n=71,59,56) | 1.30 Percent change | Standard Error 2.12 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=25th Percentile (n=88,102,100) | 2.31 Percent change | Standard Error 1.66 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <25th Percentile (n=37,28,21) | 5.99 Percent change | Standard Error 4.22 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP >=75th Percentile (n=25,40,32) | 2.97 Percent change | Standard Error 3.33 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline SP <75th Percentile (n=100,90,89) | 2.94 Percent change | Standard Error 1.75 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 high (n=63,62,57) | 4.52 Percent change | Standard Error 2.39 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Th2 low (n=57,55,55) | 0.13 Percent change | Standard Error 1.72 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC >=150 cells/mcgL (n=81,89,75) | 4.67 Percent change | Standard Error 2.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <150 cells/mcgL (n=39,34,40) | -0.40 Percent change | Standard Error 2 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Chronic OCS use (n=20,21,16) | -0.48 Percent change | Standard Error 5.31 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline PBEC <300 cells/mcgL (n=75,72,76) | 2.01 Percent change | Standard Error 1.89 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility >=12% (n=49,36,41) | 11.80 Percent change | Standard Error 3.48 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Baseline FEV1 reversibility <12% (n=76,92,80) | -1.66 Percent change | Standard Error 1.28 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | 2 asthma exacerbations (n=84,81,82) | 3.57 Percent change | Standard Error 2.04 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | > 2 but < 6 asthma exacerbations (n=41,49,40) | 1.63 Percent change | Standard Error 2.17 |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Percent Change From Baseline in Prebronchodilator FEV1 at Week 53 in Subgroups | Without chronic OCS use (n=105,109,106) | 3.45 Percent change | Standard Error 1.59 |
Comparison: Baseline serum periostin \>= medianp-value: 0.05795% CI: [-0.21, 13.79]Repeated measure model
Comparison: Baseline serum periostin \>= medianp-value: 0.87495% CI: [-6.54, 7.68]Repeated measure model
Comparison: Baseline serum periostin \< medianp-value: 0.02895% CI: [0.8, 13.95]Repeated measure model
Comparison: Baseline serum periostin \< medianp-value: 0.74595% CI: [-5.48, 7.66]Repeated measure model
Comparison: Baseline serum periostin \>= 25th percentilep-value: 0.01195% CI: [1.66, 12.58]Repeated measure model
Comparison: Baseline serum periostin \>= 25th percentilep-value: 0.86395% CI: [-5.93, 4.97]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.22195% CI: [-3.8, 16.27]Repeated measure model
Comparison: Baseline serum periostin \< 25th percentilep-value: 0.10895% CI: [-1.91, 19.07]Repeated measure model
Comparison: Baseline serum periostin \>= 75th percentilep-value: 0.0995% CI: [-1.57, 21.35]Repeated measure model
Comparison: Baseline serum periostin \>= 75th percentilep-value: 0.90895% CI: [-11.19, 12.59]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.01395% CI: [1.41, 11.64]Repeated measure model
Comparison: Baseline serum periostin \< 75th percentilep-value: 0.63595% CI: [-3.84, 6.29]Repeated measure model
Comparison: Th2 highp-value: 0.01495% CI: [1.84, 15.94]Repeated measure model
Comparison: Th2 highp-value: 0.2895% CI: [-3.19, 11.02]Repeated measure model
Comparison: Th2 lowp-value: 0.29295% CI: [-2.78, 9.22]Repeated measure model
Comparison: Th2 lowp-value: 0.69195% CI: [-6.99, 4.64]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 150 cells/μLp-value: 0.00495% CI: [2.85, 14.81]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 150 cells/μLp-value: 0.17795% CI: [-1.92, 10.43]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.15995% CI: [-2.39, 14.5]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 150 cells/μLp-value: 0.85795% CI: [-8.63, 7.18]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.00295% CI: [5.28, 22.22]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \>= 300 cells/μLp-value: 0.24395% CI: [-3.56, 14.02]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μLp-value: 0.14495% CI: [-1.5, 10.24]Repeated measure model
Comparison: Baseline peripheral blood eosinophil count \< 300 cells/μp-value: 0.80495% CI: [-5.01, 6.46]Baseline peripheral blood eosinophil cou
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.02995% CI: [1.15, 21.23]Repeated measure model
Comparison: Baseline FEV1 reversibility \>= 12%p-value: 0.88795% CI: [-9.19, 10.62]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.00295% CI: [2.76, 12.59]Repeated measure model
Comparison: Baseline FEV1 reversibility \< 12%p-value: 0.26895% CI: [-2.15, 7.74]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.00395% CI: [2.64, 13.01]Repeated measure model
Comparison: 2 asthma exacerbations in the past yearp-value: 0.36195% CI: [-2.78, 7.62]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.18595% CI: [-3.06, 15.75]Repeated measure model
Comparison: \> 2 but \< 6 asthma exacerbations in the past yearp-value: 0.98695% CI: [-9.5, 9.34]Repeated measure model
Comparison: Chronic OCS usep-value: 0.91295% CI: [-14.7, 16.44]Repeated measure model
Comparison: Chronic OCS usep-value: 0.8695% CI: [-17.76, 14.84]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.00295% CI: [2.76, 12.36]Repeated measure model
Comparison: Without chronic OCS usep-value: 0.60195% CI: [-3.51, 6.06]Repeated measure model
Secondary
Severe Annual Asthma Exacerbation Rate (AER)
Severe annualized AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed or administered by the investigator; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. An asthma exacerbation event was considered resolved 7 days after the last dose of oral corticosteroids is administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Total | Severe Annual Asthma Exacerbation Rate (AER) | 0.17 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Annual Asthma Exacerbation Rate (AER) | 0.11 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Annual Asthma Exacerbation Rate (AER) | 0.10 AER events/person-year |
Comparison: The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs \>2 but =\<6), atopic asthma status (atopic/non-atopic), chronic OCS use (presence vs absence) and geographical region as the covariates.p-value: 0.29395% CI: [0.26, 1.51]Poisson regression
Comparison: The 95% CI for rate ratio were estimated from the Poisson regression with treatment group, age, gender, number of exacerbations in past year (2 vs \>2 but =\<6), atopic asthma status (atopic/non-atopic), chronic OCS use (presence vs absence) and geographical region as the covariates.p-value: 0.2795% CI: [0.27, 1.44]Poisson regression
Secondary
Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup FEV1 reversibility. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 0.11 AER events/person-year |
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.20 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 0.13 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.10 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility >=12% (n=57,43,49) | 0.13 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline FEV1 Reversibility | Reversibility <12% (n=91,101,97) | 0.09 AER events/person-year |
Comparison: Baseline FEV1 reversibility \>=12%p-value: 0.97595% CI: [0.14, 7.67]Poisson regression
Comparison: Baseline FEV1 reversibility \>=12%p-value: 0.47395% CI: [0.41, 6.67]Poisson regression
Comparison: Baseline FEV1 reversibility \<12%p-value: 0.09995% CI: [0.21, 1.14]Poisson regression
Comparison: Baseline FEV1 reversibility \<12%p-value: 0.14895% CI: [0.13, 1.36]Poisson regression
Secondary
Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup baseline peripheral blood eosinophil count. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 0.22 AER events/person-year |
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.13 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 0.16 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.08 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | >= 300 cells/mcgL (n=54,60,50) | 0.15 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline Peripheral Blood Eosinophil Count | < 300 cells/mcgL (n=89,82,94) | 0.08 AER events/person-year |
Comparison: Baseline eosinophil count \>=300 cells/mcgLp-value: 0.13395% CI: [0.19, 1.25]Poisson regression
Comparison: Baseline eosinophil count \>=300 cells/mcgLp-value: 0.24195% CI: [0.13, 1.67]Poisson regression
Comparison: Baseline eosinophil count \<300 cells/mcgLp-value: 0.5195% CI: [0.12, 2.84]Poisson regression
Comparison: Baseline eosinophil count \<300 cells/mcgLp-value: 0.66195% CI: [0.19, 2.85]Poisson regression
Secondary
Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin
Severe AER was assessed based on AER data up to Week 53. Annualized AER was assessed based on AER data up to Week 53. An asthma exacerbation defined as a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 consecutive days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 consecutive days. It was considered resolved 7 days after the last dose of OCS administered (10 days after an injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER evaluated by subgroup baseline serum periostin. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 0.25 AER events/person-year |
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.10 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 0.08 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.14 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | >= median (n=67,81,79) | 0.12 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by Baseline Serum Periostin | < median (n=84,69,71) | 0.08 AER events/person-year |
Comparison: Baseline Serum Periostin \>=Medianp-value: 0.04695% CI: [0.06, 0.98]Poisson regression
Comparison: Baseline Serum Periostin \>=Medianp-value: 0.19795% CI: [0.15, 1.48]Poisson regression
Comparison: Baseline Serum Periostin \< Medianp-value: 0.70895% CI: [0.5, 2.79]Poisson regression
Comparison: Baseline Serum Periostin \< Medianp-value: 0.59495% CI: [0.48, 3.57]Poisson regression
Secondary
Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status
Severe AER was assessed based on AER data up to Week 53. An asthma exacerbation is a progressive increase of asthma symptoms that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed; or 2) participant initiation of systemic corticosteroids for a duration of at least 3 days. It was considered resolved 7 days after last dose of OCS administered (10 days after injectable corticosteroid). Courses of corticosteroids initiated after this time period were considered a separate new asthma exacerbation. Severe AER was evaluated by subgroup Th2 status. Th2-high include participants who had IgE \>100 IU/mL and blood eosinophils \>=0.14\*10\^9/Liter. Th2 low would include participants who do not meet Th2 high status. Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 0.12 AER events/person-year |
| Placebo Total | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.21 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 0.12 AER events/person-year |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.05 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 high (n=70,74,67) | 0.06 AER events/person-year |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Severe Asthma Exacerbation Rate (AER) by T-helper-2 (Th2) Status | Th2 Low (n=73,61,72) | 0.12 AER events/person-year |
Comparison: Th2 highp-value: 0.69895% CI: [0.31, 2.19]Poisson regression
Comparison: Th2 highp-value: 0.29995% CI: [0.18, 1.7]Poisson regression
Comparison: Th2 Lowp-value: 0.10595% CI: [0.05, 1.34]Poisson regression
Comparison: Th2 Lowp-value: 0.57695% CI: [0.2, 2.47]Poisson regression
Secondary
Time to First Exacerbation Through Week 53
Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Total | Time to First Exacerbation Through Week 53 | NA days |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Time to First Exacerbation Through Week 53 | NA days |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Time to First Exacerbation Through Week 53 | NA days |
p-value: 0.25795% CI: [0.57, 1.16]Regression, Cox
p-value: 0.22595% CI: [0.56, 1.15]Regression, Cox
Secondary
Time to First Severe Exacerbation Through Week 53
Data were summarized together for 'Placebo, Q2W' and 'Placebo, Q2/4W' arms.
Time frame: Week 1 up to Week 53
Population: The ITT population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Total | Time to First Severe Exacerbation Through Week 53 | NA days |
| Tralokinumab 300 mg, Q2W - Cohort 1 | Time to First Severe Exacerbation Through Week 53 | NA days |
| Tralokinumab 300 mg, Q2/4W - Cohort 2 | Time to First Severe Exacerbation Through Week 53 | NA days |
p-value: 0.53895% CI: [0.37, 1.68]Regression, Cox
p-value: 0.56195% CI: [0.37, 1.71]Regression, Cox