Asthma
Conditions
Keywords
Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma
Brief summary
A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma
Detailed description
This is a multicentre, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 1060 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.
Interventions
BIOLOGICALExperimental: Tezepelumab
Tezepelumab subcutaneous injection
OTHERPlacebo
Placebo subcutaneous injection
Sponsors
Amgen
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blind
Intervention model description
Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age. 12-80 * Documented physician-diagnosed asthma for at least 12 months * Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months. * Documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months. * At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months. * Morning pre-BD FEV1 \<80% predicted normal (\<90% for subjects 12-17 yrs) * Evidence of asthma as documented by either: Documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening. * Documented history of at least 2 asthma exacerbation events within 12 months. * ACQ-6 score ≥1.5 at screening and on day of randomization
Exclusion criteria
* Pulmonary disease other than asthma. * History of cancer. * History of a clinically significant infection. * Current smokers or subjects with smoking history ≥10 pack-years and subjects using vaping products, including electronic cigarettes. * History of chronic alcohol or drug abuse within 12 months. * Hepatitis B, C or HIV. * Pregnant or breastfeeding. * History of anaphylaxis following any biologic therapy. * Subject randomized in the current study or previous tezepelumab studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL | From randomisation to Study Week 52. | The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils \< 300 cells/uL |
| Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma | From randomisation to Study Week 52. | The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint) | From randomisation to Study Week 52 | Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). |
| Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) | From randomisation to Study Week 52 | Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses. |
| Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) | From randomisation to Study Week 52 | Mean change from baseline at Week 52 in Asthma Symptom Diary. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4, where 0 indicates no asthma symptoms. |
| Time to First Asthma Exacerbation | From randomisation to Study Week 52 | Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF. |
| Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) | From randomisation to Study Week 52 | Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site |
| Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 | From randomisation to Study Week 52 | Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x \[number of night nebulizer times\] + number of daytime inhaler puffs + 2 x \[number of day nebulizer times\]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use. |
| Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 | From randomisation to Study Week 52 | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. |
| Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 | From randomisation to Study Week 52 | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Class productivity loss is derived by sum of percentage of missed class hours due to asthma and product of percentage of actual hours in class times degree of asthma affecting productivity while in class. Percentage of missed hours in class due to asthma is calculated by number of hours in class missed due to asthma divided by total number of hours in class missed plus number of hours actually in class. |
| Activity Impairment at Week 52 | From randomisation to Study Week 52 | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage. |
| Pharmacokinetics of Tezepelumab | Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64 | Mean serum trough PK concentrations taken pre-dose at each visit |
| Mean Change From Baseline at Week 52 in EQ-5D-5L VAS | At Study Week 52 | Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state. |
| Clinicians Global Impression of Change at Week 52 | From randomisation to Study Week 52 | CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse) |
| Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint) | From randomisation to Study Week 52 | Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. |
| Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation | From randomisation to Study Week 52 | The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF) |
| Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation | From randomisation to Study Week 52 | Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation. |
| Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation | From randomisation to Study Week 52 | The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period. |
| Patients Global Impression of Change at Week 52 | From randomisation to Study Week 52 | PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse). |
| Patients Global Impression of Severity at Week 52 | At Study Week 52 | PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms |
| Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) | From randomisation to Study Week 52 | Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL) |
| Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) | From randomisation to Study Week 52 | Mean change from baseline at Study Week 52 in total serum IgE (IU/mL) |
| Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | From randomisation to Study Week 52 | Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks |
| Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | From randomisation to Study Week 52 | Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data. |
| Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | From randomisation to Study Week 52 | Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data. |
| Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 | From randomisation to Study Week 52 | Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean. |
| Immunogenecity of Tezepelumab | Baseline, and from time of first dose at Week 0 to end of study at Week 64. | Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post baseline assessments (with \>=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA. |
| Proportion of Subjects Who Had no Asthma Exacerbations | From randomisation to Study Week 52 | The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate Associated With Hospitalisations | From randomisation to Study Week 52 | The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization |
| Annual Asthma Exacerbation Rate Using Adjudicated Data | From randomisation to Study Week 52 | The annualized exacerbation rate is based on exacerbations as defined for the primary endpoint, but any hospitalisation and ER visits which are adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses. |
| Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data | From randomisation to Study Week 52 | The annualized exacerbation rate is based on exacerbations associated with hospitalisations or ER visits, where hospitalisation and ER visits adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses. |
Countries
Argentina, Australia, Austria, Brazil, Canada, France, Germany, Israel, Japan, Russia, Saudi Arabia, South Africa, South Korea, Taiwan, Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
A total of 1061 subjects were randomised at 231 centres in 17 countries to receive treatment with tezepelumab 210mg Q4W or placebo,
Pre-assignment details
Of the 1061 randomised, 1059 (99.8%) subjects received treatment. 82 (7.7%) of the subjects randomised and treated were adolescents.
Participants by arm
| Arm | Count |
|---|---|
| Tezepelumab 210mg Q4W Tezepelumab administered every 4 weeks subcutaneously | 528 |
| Placebo Placebo administered subcutaneously | 531 |
| Total | 1,059 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Did not receive treatment / Non-compliance with protocol / did not complete safety follow-up visits | 3 | 4 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 15 |
Baseline characteristics
| Characteristic | Tezepelumab 210mg Q4W | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 41 Participants | 41 Participants | 82 Participants |
| Age, Categorical >=65 years | 96 Participants | 74 Participants | 170 Participants |
| Age, Categorical Between 18 and 65 years | 391 Participants | 416 Participants | 807 Participants |
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 16.3 | 49.0 Years STANDARD_DEVIATION 15.9 | 49.5 Years STANDARD_DEVIATION 16.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 146 Participants | 149 Participants | 295 Participants |
| Race/Ethnicity, Customized Black of African American | 30 Participants | 31 Participants | 61 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 83 Participants | 81 Participants | 164 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 445 Participants | 450 Participants | 895 Participants |
| Race/Ethnicity, Customized Other | 19 Participants | 23 Participants | 42 Participants |
| Race/Ethnicity, Customized White | 332 Participants | 327 Participants | 659 Participants |
| Sex: Female, Male Female | 335 Participants | 337 Participants | 672 Participants |
| Sex: Female, Male Male | 193 Participants | 194 Participants | 387 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 528 | 2 / 531 |
| other Total, other adverse events | 306 / 528 | 331 / 531 |
| serious Total, serious adverse events | 52 / 528 | 73 / 531 |
Outcome results
Primary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma
The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set)
Time frame: From randomisation to Study Week 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma | 0.93 events per year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma | 2.10 events per year |
p-value: <0.00195% CI: [0.37, 0.53]Negative Binomial
Primary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL
The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils \< 300 cells/uL
Time frame: From randomisation to Study Week 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL | 1.02 events per year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL | 1.73 events per year |
p-value: <0.00195% CI: [0.46, 0.75]Negative Binomial
Secondary
Activity Impairment at Week 52
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Activity Impairment at Week 52 | -20.0 Percentage of activity impairment | Standard Deviation 28.6 |
| Placebo | Activity Impairment at Week 52 | -17.9 Percentage of activity impairment | Standard Deviation 27.1 |
Secondary
Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation
The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF)
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation | 0.06 events per year |
| Placebo | Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation | 0.28 events per year |
Secondary
Clinicians Global Impression of Change at Week 52
CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse)
Time frame: From randomisation to Study Week 52
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Minimally improved | 98 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Minimally worse | 11 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Much improved | 199 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Much worse | 2 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | No change | 77 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Very much worse | 0 Participants |
| Tezepelumab 210mg Q4W | Clinicians Global Impression of Change at Week 52 | Very much improved | 96 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Very much worse | 1 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Very much improved | 60 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Much improved | 132 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Minimally improved | 131 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | No change | 130 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Minimally worse | 19 Participants |
| Placebo | Clinicians Global Impression of Change at Week 52 | Much worse | 4 Participants |
Secondary
Immunogenecity of Tezepelumab
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post baseline assessments (with \>=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.
Time frame: Baseline, and from time of first dose at Week 0 to end of study at Week 64.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Only baseline ADA positive | 14 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Treatment induced ADA positive | 9 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Any baseline ADA positive | 17 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Treatment boosted ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Any post-baseline ADA positive | 12 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Treatment emergent ADA positive | 10 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | ADA positive at baseline and/or post-baseline | 26 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | ADA persistently positive | 4 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | ADA transiently positive | 8 Participants |
| Tezepelumab 210mg Q4W | Immunogenecity of Tezepelumab | Both baseline and >= 1 post-baseline ADA positive | 3 Participants |
| Placebo | Immunogenecity of Tezepelumab | ADA transiently positive | 18 Participants |
| Placebo | Immunogenecity of Tezepelumab | ADA positive at baseline and/or post-baseline | 44 Participants |
| Placebo | Immunogenecity of Tezepelumab | Any baseline ADA positive | 25 Participants |
| Placebo | Immunogenecity of Tezepelumab | Only baseline ADA positive | 8 Participants |
| Placebo | Immunogenecity of Tezepelumab | Any post-baseline ADA positive | 36 Participants |
| Placebo | Immunogenecity of Tezepelumab | Both baseline and >= 1 post-baseline ADA positive | 17 Participants |
| Placebo | Immunogenecity of Tezepelumab | Treatment induced ADA positive | 18 Participants |
| Placebo | Immunogenecity of Tezepelumab | Treatment boosted ADA positive | 2 Participants |
| Placebo | Immunogenecity of Tezepelumab | Treatment emergent ADA positive | 20 Participants |
| Placebo | Immunogenecity of Tezepelumab | ADA persistently positive | 18 Participants |
Secondary
Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint)
Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.
Time frame: From randomisation to Study Week 52
Population: Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) | -1.53 Scale of score | Standard Error 0.045 |
| Placebo | Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) | -1.20 Scale of score | Standard Error 0.046 |
p-value: <0.00195% CI: [-0.46, -0.2]Mixed Models Analysis
Secondary
Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint)
Mean change from baseline at Week 52 in Asthma Symptom Diary. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4, where 0 indicates no asthma symptoms.
Time frame: From randomisation to Study Week 52
Population: Number of participants analyzed is the number of subjects with a weekly mean at Week 52. All subjects from the Full Analysis Set with at least one change from baseline weekly mean at any post-baseline week contributes to the analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) | -0.70 Scale of score | Standard Error 0.027 |
| Placebo | Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) | -0.59 Scale of score | Standard Error 0.027 |
p-value: 0.00495% CI: [-0.19, -0.04]Mixed Models Analysis
Secondary
Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL)
Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) | -170.02 cells/uL | Standard Error 9.222 |
| Placebo | Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) | -40.15 cells/uL | Standard Error 9.254 |
Secondary
Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb)
Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) | -17.29 ppb | Standard Error 1.156 |
| Placebo | Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) | -3.46 ppb | Standard Error 1.165 |
Secondary
Mean Change From Baseline at Week 52 in EQ-5D-5L VAS
Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time frame: At Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in EQ-5D-5L VAS | 14.64 scale of score | Standard Error 0.708 |
| Placebo | Mean Change From Baseline at Week 52 in EQ-5D-5L VAS | 11.86 scale of score | Standard Error 0.712 |
Secondary
Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint)
Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Time frame: From randomisation to Study Week 52
Population: Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint) | 0.23 Litre | Standard Error 0.018 |
| Placebo | Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint) | 0.10 Litre | Standard Error 0.018 |
p-value: <0.00195% CI: [0.08, 0.18]Mixed Models Analysis
Secondary
Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint)
Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).
Time frame: From randomisation to Study Week 52
Population: Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint) | 1.48 Scale of score | Standard Error 0.049 |
| Placebo | Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint) | 1.14 Scale of score | Standard Error 0.049 |
p-value: <0.00195% CI: [0.2, 0.47]Mixed Models Analysis
Secondary
Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL)
Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) | -164.38 IU/mL | Standard Error 34.414 |
| Placebo | Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) | 43.61 IU/mL | Standard Error 34.542 |
Secondary
Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Class productivity loss is derived by sum of percentage of missed class hours due to asthma and product of percentage of actual hours in class times degree of asthma affecting productivity while in class. Percentage of missed hours in class due to asthma is calculated by number of hours in class missed due to asthma divided by total number of hours in class missed plus number of hours actually in class.
Time frame: From randomisation to Study Week 52
Population: The class productivity loss is only applicable to subjects attending school, which is a subset of the study population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 | -14.03 Percentage of class productivity loss | Standard Deviation 33 |
| Placebo | Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 | -24.72 Percentage of class productivity loss | Standard Deviation 26.48 |
Secondary
Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52
Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x \[number of night nebulizer times\] + number of daytime inhaler puffs + 2 x \[number of day nebulizer times\]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 | -2.53 weekly mean rescue medication use | Standard Error 0.137 |
| Placebo | Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 | -2.36 weekly mean rescue medication use | Standard Error 0.137 |
Secondary
Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)
Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | 23.87 L/min | Standard Error 3.075 |
| Placebo | Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | 9.01 L/min | Standard Error 3.094 |
Secondary
Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)
Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | 34.57 L/min | Standard Error 3.051 |
| Placebo | Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) | 18.01 L/min | Standard Error 3.074 |
Secondary
Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52
Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 | -33.51 percentage of nights with awakenings | Standard Error 1.381 |
| Placebo | Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 | -30.22 percentage of nights with awakenings | Standard Error 1.387 |
Secondary
Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked.
Time frame: From randomisation to Study Week 52
Population: The work productivity loss is only applicable to subjects who were employed, which is a subset of the study population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 | -20.16 Percentage of work productivity loss | Standard Deviation 30.31 |
| Placebo | Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 | -16.58 Percentage of work productivity loss | Standard Deviation 29.46 |
Secondary
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks
Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks
Time frame: From randomisation to Study Week 52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Hospitalisation | 17 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Emergency Room visit | 23 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Unscheduled visit to specialist | 187 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Home visit | 9 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Telephone call | 101 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Ambulance transport | 4 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Telephone call | 133 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Hospitalisation | 37 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Home visit | 10 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Emergency Room visit | 50 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Ambulance transport | 12 Participants |
| Placebo | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks | Unscheduled visit to specialist | 231 Participants |
Secondary
Patients Global Impression of Change at Week 52
PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse).
Time frame: From randomisation to Study Week 52
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Minimally improved | 71 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Minimally worse | 6 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Much Improved | 103 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Much worse | 4 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | No change | 39 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Very much worse | 1 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Change at Week 52 | Very much improved | 255 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Very much worse | 1 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Very much improved | 182 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Much Improved | 94 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Minimally improved | 76 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | No change | 99 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Minimally worse | 8 Participants |
| Placebo | Patients Global Impression of Change at Week 52 | Much worse | 6 Participants |
Secondary
Patients Global Impression of Severity at Week 52
PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms
Time frame: At Study Week 52
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | No symptoms | 118 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | Very mild symptoms | 138 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | Mild symptoms | 110 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | Moderate symptoms | 99 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | Severe symptoms | 14 Participants |
| Tezepelumab 210mg Q4W | Patients Global Impression of Severity at Week 52 | Very severe symptoms | 0 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | Severe symptoms | 19 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | No symptoms | 78 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | Moderate symptoms | 111 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | Very mild symptoms | 128 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | Very severe symptoms | 2 Participants |
| Placebo | Patients Global Impression of Severity at Week 52 | Mild symptoms | 128 Participants |
Secondary
Pharmacokinetics of Tezepelumab
Mean serum trough PK concentrations taken pre-dose at each visit
Time frame: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64
Population: Number of subjects who received at least one dose of IP. Number analysed at each timepoint is a subset of this based on subjects who had sample results available at that timepoint. The placebo arm is not applicable since it is not the experimental product.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Baseline | 0 ug/mL | Geometric Coefficient of Variation 0 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 4 | 10.1573 ug/mL | Geometric Coefficient of Variation 74.51 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 12 | 18.7396 ug/mL | Geometric Coefficient of Variation 48.53 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 24 | 20.1924 ug/mL | Geometric Coefficient of Variation 51.77 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 36 | 19.5246 ug/mL | Geometric Coefficient of Variation 55.58 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 52 | 19.8894 ug/mL | Geometric Coefficient of Variation 70.04 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 64 | 1.7675 ug/mL | Geometric Coefficient of Variation 171.86 |
Secondary
Proportion of Subjects Who Had no Asthma Exacerbations
The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tezepelumab 210mg Q4W | Proportion of Subjects Who Had no Asthma Exacerbations | 54.2 Percentage |
| Placebo | Proportion of Subjects Who Had no Asthma Exacerbations | 38.6 Percentage |
Secondary
Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation
The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tezepelumab 210mg Q4W | Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation | 92.4 Percentage |
| Placebo | Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation | 85.1 Percentage |
Secondary
Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation
Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tezepelumab 210mg Q4W | Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation | 4.7 Percentage |
| Placebo | Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation | 12.2 Percentage |
Secondary
Time to First Asthma Exacerbation
Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tezepelumab 210mg Q4W | Time to First Asthma Exacerbation | 231 Participants |
| Placebo | Time to First Asthma Exacerbation | 319 Participants |
Other Pre-specified
Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data
The annualized exacerbation rate is based on exacerbations associated with hospitalisations or ER visits, where hospitalisation and ER visits adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data | 0.08 events per year |
| Placebo | Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data | 0.31 events per year |
Other Pre-specified
Annual Asthma Exacerbation Rate Associated With Hospitalisations
The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate Associated With Hospitalisations | 0.03 events per year |
| Placebo | Annual Asthma Exacerbation Rate Associated With Hospitalisations | 0.19 events per year |
Other Pre-specified
Annual Asthma Exacerbation Rate Using Adjudicated Data
The annualized exacerbation rate is based on exacerbations as defined for the primary endpoint, but any hospitalisation and ER visits which are adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.
Time frame: From randomisation to Study Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate Using Adjudicated Data | 0.94 events per year |
| Placebo | Annual Asthma Exacerbation Rate Using Adjudicated Data | 2.14 events per year |