Asthma
Conditions
Keywords
Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma
Brief summary
A Regional, Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults with Severe Uncontrolled Asthma
Detailed description
This is a regional, multicentre, randomized, double-blind, placebo controlled, parallel group, phase 3 study designed to evaluate the efficacy and safety of 210 mg Q4W (SC) of tezepelumab in adults with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 396 participants will be randomized regionally (China/non-China). Participants 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
Participants will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age. 18-80 * Documented physician-diagnosed asthma for at least 12 months * Participants who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 6 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 * 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, and at least one of the exacerbations should occur during the treatment of medium-to-high dose ICS. * 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 participants with smoking history ≥10 pack-yrs. * 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. * participant randomized in the current study or previous tezepelumab studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate (AERR) | Randomization to Week 52 | The annual exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score at Week 52 | Randomization to 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 participants. 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 in Asthma Control Questionnaire-6 (ACQ-6) Score at Week 52 | Randomization to Week 52 | Mean 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 in Weekly Mean Daily Asthma Symptom Diary Score at Week 52 | Randomization to Week 52 | Mean change from baseline in Asthma Symptom Diary score as compared to placebo at Week 52. 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. A higher value indicates a worse outcome. 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. |
| Time to First Asthma Exacerbation | Randomization to Week 52 | Time to the first occurrence of asthma exacerbation post randomization, presented as number of participants with at least one asthma exacerbation reported in the eCRF |
| Mean Change From Baseline in Fractional Exhaled Nitric Oxide at Week 52 | Randomization to Week 52 | Mean change from baseline in FENO (ppb) at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers |
| Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Randomization to Week 52 | Number of participants with asthma specific resource utilization (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks. |
| Pharmacokinetics of Tezepelumab | Baseline, Week 24, Week 52, Week 64 | Mean serum trough PK concentrations taken pre-dose at each scheduled visit to evaluate the pharmacokinetics (PK) of tezepelumab |
| Mean Change From Baseline in EQ-5D-5L VAS Score at Week 52 | At Week 52 | Mean change from baseline in EQ-5D-5L VAS at week 52. EQ-5D-5L visual analogue scale (VAS) allows participants to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state. |
| Mean Change From Baseline in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Randomization to 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. |
| Mean Change From Baseline in Total Serum IgE (IU/mL) at Week 52 | Randomization to Week 52 | Mean change from baseline in IgE at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers. |
| Mean Change From Baseline in Night Time Awakenings (Percentage) at Week 52 | Randomization to Week 52 | Mean change from baseline in night time awakenings due to asthma at Week 52. Night time awakenings percentage is defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with available data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean. |
| Immunogenicity of Tezepelumab | Baseline to 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. |
| Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 | Randomization to 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 Home Based Morning Peak Expiratory Flow (PEF) at Week 52 | Randomization to Week 52 | Mean change from baseline in home based morning PEF (L/min) at Week 52. Home PEF testing was performed by participant 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 | Randomization to Week 52 | Mean change from baseline in home based evening PEF (L/min) at Week 52. Home PEF testing was performed by participant 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. |
| Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalization | Randomization to Week 52 | The annual 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 Participants Who Had no Asthma Exacerbations | Randomization to Week 52 | The proportion of participants who had no asthma exacerbations is presented as the percentage of participants with no exacerbations. This is defined as participants who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period. |
| Mean Change From Baseline in Blood Eosinophils (Cells/uL) at Week 52 | Randomization to Week 52 | Mean change from baseline in blood eosinophil counts at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers. |
Countries
China, Philippines, South Korea
Participant flow
Recruitment details
A total of 401 participants were randomized at 74 sites in 3 Asian countries to receive treatment with tezepelumab 210mg Q4W or placebo.
Pre-assignment details
Of the 401 randomized, 400 (99.8%) participants received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Tezepelumab 210mg Q4W Tezepelumab administered every 4 weeks subcutaneously | 201 |
| Placebo Placebo administered subcutaneously | 199 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Due to COVID-19 pandemic | 5 | 2 |
| Overall Study | Other than above | 0 | 1 |
| Overall Study | Protocol-specified withdrawal criterion met | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 21 |
Baseline characteristics
| Characteristic | Tezepelumab 210mg Q4W | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 32 Participants | 67 Participants |
| Age, Categorical Between 18 and 65 years | 166 Participants | 167 Participants | 333 Participants |
| Age, Continuous | 52.3 Years STANDARD_DEVIATION 12.4 | 54.3 Years STANDARD_DEVIATION 10.3 | 53.3 Years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 201 Participants | 199 Participants | 400 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 201 Participants | 199 Participants | 400 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 119 Participants | 112 Participants | 231 Participants |
| Sex: Female, Male Male | 82 Participants | 87 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 201 | 2 / 199 |
| other Total, other adverse events | 114 / 201 | 125 / 199 |
| serious Total, serious adverse events | 16 / 201 | 36 / 199 |
Outcome results
Primary
Annual Asthma Exacerbation Rate (AERR)
The annual exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks
Time frame: Randomization to Week 52
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate (AERR) | 0.42 Events per year |
| Placebo | Annual Asthma Exacerbation Rate (AERR) | 1.63 Events per year |
p-value: <0.00195% CI: [0.17, 0.39]Negative Binomial Regression
Secondary
Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalization
The annual 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: Randomization to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tezepelumab 210mg Q4W | Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalization | 0.07 Events per year |
| Placebo | Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalization | 0.18 Events per year |
Secondary
Immunogenicity 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 to Week 64
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Only baseline ADA positive | 10 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | TE-ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | ADA positive at baseline and/or post-baseline | 11 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | ADA persistently positive | 1 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | ADA transiently positive | 0 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Treatment-boosted ADA positive | 0 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Any post-baseline ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Treatment-induced ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Both baseline and at least one post-baseline ADA positive | 0 Participants |
| Tezepelumab 210mg Q4W | Immunogenicity of Tezepelumab | Any baseline ADA positive | 10 Participants |
| Placebo | Immunogenicity of Tezepelumab | ADA positive at baseline and/or post-baseline | 18 Participants |
| Placebo | Immunogenicity of Tezepelumab | Only baseline ADA positive | 7 Participants |
| Placebo | Immunogenicity of Tezepelumab | Treatment-boosted ADA positive | 1 Participants |
| Placebo | Immunogenicity of Tezepelumab | ADA transiently positive | 1 Participants |
| Placebo | Immunogenicity of Tezepelumab | Any baseline ADA positive | 14 Participants |
| Placebo | Immunogenicity of Tezepelumab | Any post-baseline ADA positive | 11 Participants |
| Placebo | Immunogenicity of Tezepelumab | Both baseline and at least one post-baseline ADA positive | 7 Participants |
| Placebo | Immunogenicity of Tezepelumab | Treatment-induced ADA positive | 4 Participants |
| Placebo | Immunogenicity of Tezepelumab | TE-ADA positive | 5 Participants |
| Placebo | Immunogenicity of Tezepelumab | ADA persistently positive | 10 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Only baseline ADA positive | 2 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Any post-baseline ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Both baseline and at least one post-baseline ADA positive | 0 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA positive at baseline and/or post-baseline | 3 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Treatment-induced ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Treatment-boosted ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA transiently positive | 0 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | TE-ADA positive | 1 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | Any baseline ADA positive | 2 Participants |
| Tezepelumab 210mg Q4W (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA persistently positive | 1 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | TE-ADA positive | 2 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Treatment-boosted ADA positive | 0 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Any post-baseline ADA positive | 2 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Treatment-induced ADA positive | 2 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA persistently positive | 1 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Any baseline ADA positive | 5 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Both baseline and at least one post-baseline ADA positive | 0 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA transiently positive | 1 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | ADA positive at baseline and/or post-baseline | 7 Participants |
| Placebo (Non-China Cohort) | Immunogenicity of Tezepelumab | Only baseline ADA positive | 5 Participants |
Secondary
Mean Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) Score at Week 52
Mean 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: Randomization to Week 52
Population: All participants from the Full Analysis Set with at least one change from baseline value at any post-baseline visit contribute to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) Score at Week 52 | -1.34 Scores on a scale | Standard Error 0.058 |
| Placebo | Mean Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) Score at Week 52 | -1.03 Scores on a scale | Standard Error 0.059 |
p-value: <0.00195% CI: [-0.47, -0.15]Mixed Models Analysis
Secondary
Mean Change From Baseline in Blood Eosinophils (Cells/uL) at Week 52
Mean change from baseline in blood eosinophil counts at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Time frame: Randomization to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Blood Eosinophils (Cells/uL) at Week 52 | -193.44 cells/uL | Standard Error 21.538 |
| Placebo | Mean Change From Baseline in Blood Eosinophils (Cells/uL) at Week 52 | -38.86 cells/uL | Standard Error 21.984 |
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: Randomization to 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 | -0.81 Inhalations and nebulizers per week | Standard Error 0.064 |
| Placebo | Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 | -0.70 Inhalations and nebulizers per week | Standard Error 0.066 |
Secondary
Mean Change From Baseline in EQ-5D-5L VAS Score at Week 52
Mean change from baseline in EQ-5D-5L VAS at week 52. EQ-5D-5L visual analogue scale (VAS) allows participants to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time frame: At Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in EQ-5D-5L VAS Score at Week 52 | 12.80 Scores on a scale | Standard Error 1.009 |
| Placebo | Mean Change From Baseline in EQ-5D-5L VAS Score at Week 52 | 9.67 Scores on a scale | Standard Error 1.028 |
Secondary
Mean Change From Baseline in Fractional Exhaled Nitric Oxide at Week 52
Mean change from baseline in FENO (ppb) at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers
Time frame: Randomization to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Fractional Exhaled Nitric Oxide at Week 52 | -15.88 ppb | Standard Error 1.628 |
| Placebo | Mean Change From Baseline in Fractional Exhaled Nitric Oxide at Week 52 | -3.15 ppb | Standard Error 1.658 |
Secondary
Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52
Mean change from baseline in home based evening PEF (L/min) at Week 52. Home PEF testing was performed by participant 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: Randomization to 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 | 42.14 L/min | Standard Error 4.558 |
| Placebo | Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 | 16.81 L/min | Standard Error 4.7 |
Secondary
Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52
Mean change from baseline in home based morning PEF (L/min) at Week 52. Home PEF testing was performed by participant 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: Randomization to 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 | 46.70 L/min | Standard Error 4.586 |
| Placebo | Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 | 18.96 L/min | Standard Error 4.73 |
Secondary
Mean Change From Baseline in Night Time Awakenings (Percentage) at Week 52
Mean change from baseline in night time awakenings due to asthma at Week 52. Night time awakenings percentage is defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with available data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.
Time frame: Randomization to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Night Time Awakenings (Percentage) at Week 52 | -18.74 Percentage of nights with awakenings | Standard Error 1.035 |
| Placebo | Mean Change From Baseline in Night Time Awakenings (Percentage) at Week 52 | -15.99 Percentage of nights with awakenings | Standard Error 1.093 |
Secondary
Mean Change From Baseline in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) at 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.
Time frame: Randomization to Week 52
Population: All participants from the Full Analysis Set with at least one change from baseline value at any post-baseline visit contributes to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | 0.35 Litre | Standard Error 0.029 |
| Placebo | Mean Change From Baseline in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | 0.11 Litre | Standard Error 0.03 |
p-value: <0.00195% CI: [0.16, 0.32]Mixed Models Analysis
Secondary
Mean Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score at 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 participants. 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: Randomization to Week 52
Population: All participants from the Full Analysis Set with at least one change from baseline value at any post-baseline visit contribute to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score at Week 52 | 1.29 Scores on a scale | Standard Error 0.074 |
| Placebo | Mean Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score at Week 52 | 0.94 Scores on a scale | Standard Error 0.076 |
p-value: 0.00195% CI: [0.14, 0.55]Mixed Models Analysis
Secondary
Mean Change From Baseline in Total Serum IgE (IU/mL) at Week 52
Mean change from baseline in IgE at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Time frame: Randomization to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Total Serum IgE (IU/mL) at Week 52 | -92.77 IU/mL | Standard Error 27.46 |
| Placebo | Mean Change From Baseline in Total Serum IgE (IU/mL) at Week 52 | 0.30 IU/mL | Standard Error 28.013 |
Secondary
Mean Change From Baseline in Weekly Mean Daily Asthma Symptom Diary Score at Week 52
Mean change from baseline in Asthma Symptom Diary score as compared to placebo at Week 52. 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. A higher value indicates a worse outcome. 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.
Time frame: Randomization to Week 52
Population: All participants from the Full Analysis Set with at least one change from baseline value at any post-baseline week contribute to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Mean Change From Baseline in Weekly Mean Daily Asthma Symptom Diary Score at Week 52 | -0.61 Scores on a scale | Standard Error 0.036 |
| Placebo | Mean Change From Baseline in Weekly Mean Daily Asthma Symptom Diary Score at Week 52 | -0.44 Scores on a scale | Standard Error 0.037 |
p-value: 0.00195% CI: [-0.27, -0.06]Mixed Models Analysis
Secondary
Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks
Number of participants with asthma specific resource utilization (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks.
Time frame: Randomization to Week 52
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Hospitalisation | 4 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Emergency room visit | 5 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Unscheduled visit to specialist | 36 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Home visit | 1 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Telephone call | 28 Participants |
| Tezepelumab 210mg Q4W | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Ambulance transport | 0 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Telephone call | 55 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Hospitalisation | 13 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Home visit | 0 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Emergency room visit | 11 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Ambulance transport | 2 Participants |
| Placebo | Number of Participants With Asthma Specific Resource Utilization Over 52 Weeks | Unscheduled visit to specialist | 75 Participants |
Secondary
Pharmacokinetics of Tezepelumab
Mean serum trough PK concentrations taken pre-dose at each scheduled visit to evaluate the pharmacokinetics (PK) of tezepelumab
Time frame: Baseline, Week 24, Week 52, Week 64
Population: PK Analysis Set: participants who received at least one dose of tezepelumab. The placebo arm is not applicable. Number analyzed at each timepoint is a subset of PK Analysis Set based on participants who had sample results available at that timepoint.
| 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 24 | 21.3513 ug/mL | Geometric Coefficient of Variation 43.96 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 52 | 21.2222 ug/mL | Geometric Coefficient of Variation 41.51 |
| Tezepelumab 210mg Q4W | Pharmacokinetics of Tezepelumab | Week 64 | 1.4450 ug/mL | Geometric Coefficient of Variation 157.46 |
Secondary
Proportion of Participants Who Had no Asthma Exacerbations
The proportion of participants who had no asthma exacerbations is presented as the percentage of participants with no exacerbations. This is defined as participants 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: Randomization to Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tezepelumab 210mg Q4W | Proportion of Participants Who Had no Asthma Exacerbations | 74.6 Percentage |
| Placebo | Proportion of Participants Who Had no Asthma Exacerbations | 50.3 Percentage |
Secondary
Time to First Asthma Exacerbation
Time to the first occurrence of asthma exacerbation post randomization, presented as number of participants with at least one asthma exacerbation reported in the eCRF
Time frame: Randomization to Week 52
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tezepelumab 210mg Q4W | Time to First Asthma Exacerbation | 45 Participants |
| Placebo | Time to First Asthma Exacerbation | 89 Participants |