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    Clinical Trial Results:
    A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Participants with Severe Chronic Rhinosinusitis with Nasal Polyposis (WAYPOINT)

    Summary
    EudraCT number
    		 2020-003062-39
    Trial protocol
    		 DE   DK   HU   PL  
    Global end of trial date
    11 Dec 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D5242C00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04851964
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    151 85, Sodertalje, Sweden,
    Public contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 May 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Dec 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy and safety of repeat dosing of tezepelumab 210 mg SC versus placebo in adult participants with severe CRSwNP.
    Protection of trial subjects
    The investigator or his/her representative explained the nature of the study to the participant or his/her legally authorised representative and answered all questions regarding the study. Participants were informed that their participation was voluntary and they were free to refuse to participate and may withdraw their consent at any time and for any reason during the study. Participants or their legally authorised representative were required to sign a statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study centre. The medical record included a statement that written informed consent was obtained before the participant was enrolled in the study and the date the written consent was obtained. The authorised person obtaining the informed consent also signed the ICF. Participants must be re-consented to the most current version of the ICF(s) during their participation in the study. A copy of the ICF(s) must be provided to the participant or the participant’s legally authorised representative. Participants who were rescreened were required to sign a new ICF. The ICF contained a separate section that addresses and documents the collection and use of any mandatory and/or optional human biological samples. The investigator or authorized designee explained to each participant the objectives of the analysis to be done on the samples and any potential future use. Participants were told that they were free to refuse to participate in any optional samples or the future use and may withdraw their consent at any time and for any reason during the retention period.
    Background therapy
    		 All participants used INCS for a minimum of 4 weeks prior to Randomization (Visit 3) and continued throughout the study period. Two doses of MFNS (50μg/actuation) in each nostril twice daily (total 400μg daily) or equivalent INCS were administered unless there was a medical rationale to use the lower dose (QD) regimen. Equivalent dose referred to the highest approved country INCS dose for CRSwNP. The generic name of the INCS and the total daily dose were recorded in the eCRF.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Apr 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 63
    Country: Number of subjects enrolled
    Japan: 33
    Country: Number of subjects enrolled
    Canada: 49
    Country: Number of subjects enrolled
    Denmark: 40
    Country: Number of subjects enrolled
    Germany: 41
    Country: Number of subjects enrolled
    United Kingdom: 23
    Country: Number of subjects enrolled
    Hungary: 31
    Country: Number of subjects enrolled
    Poland: 58
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    408
    EEA total number of subjects
    203
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    353
    From 65 to 84 years
    55
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 872 participants were screened between 22Apr2021 and 23Aug2023.

    Pre-assignment
    Screening details
    		 410 were randomised to either the treatment (204 participants) or placebo (206 participants) arms of the double-blind treatment period. Two participants were randomized but not dosed. Therefore, 203 participants started in the treatment arm and 205 in the placebo arm, for a total of 408 participants.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Carer, Data analyst, Assessor, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tezepelumab
    Arm description
    		 210 mg tezepelumab injection delivered subcutaneously every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    210 mg Tezepelumab administered every 4 weeks subcutaneously
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    210 mg Q4W

    Arm title
    		 Placebo
    Arm description
    		 Matching Placebo injection delivered subcutaneously every 4 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Q4W

    Number of subjects in period 1
    		Tezepelumab Placebo
    Started
    203
    205
    Completed
    193
    174
    Not completed
    10
    31
         Adverse event, serious fatal
    -
    1
         Other biologic treatment
    -
    2
         Consent withdrawn by subject
    8
    23
         Nasal polyp surgery
    -
    2
         Severe incompliance
    -
    1
         Lost to follow-up
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tezepelumab
    Reporting group description
    		 210 mg tezepelumab injection delivered subcutaneously every 4 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Matching Placebo injection delivered subcutaneously every 4 weeks

    Reporting group values
    		 Tezepelumab Placebo Total
    Number of subjects
    		 203 205 408
    Age Categorical
    Age group at screening visit
    Units:
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 174 179 353
        >=65 years
    		 29 26 55
    Age Continuous
    Age at screening visit
    Units: years
        arithmetic mean (standard deviation)
    		 50.1 ( 13.60 ) 49.4 ( 13.69 ) -
    Sex: Female, Male
    Gender at screening visit
    Units:
        Female
    		 77 65 142
        Male
    		 126 140 266
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 3 3 6
        White
    		 150 149 299
        Native Hawaiian or other Pacific Islander
    		 0 0 0
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 46 51 97
        Other
    		 4 2 6
        Not reported
    		 0 0 0
    Race/Ethnicity, Customized
    Ethnicity group
    Units: Subjects
        Hispanic or Latino
    		 11 11 22
        Not Hispanic or Latino
    		 192 194 386

    End points

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    End points reporting groups
    Reporting group title
    Tezepelumab
    Reporting group description
    		 210 mg tezepelumab injection delivered subcutaneously every 4 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Matching Placebo injection delivered subcutaneously every 4 weeks

    Primary: Change from baseline in total nasal polyp score at Week 52

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    End point title
    		 Change from baseline in total nasal polyp score at Week 52
    End point description
    The total nasal polyp score (NPS) is the sum of the right and left nostril scores (maximum of 8), as evaluated by nasal endoscopy. Higher scores indicate greater symptom severity. The left and right score will be based on a central read with a scale from 0 to 4. Each nasal endoscopy is evaluated by two independent physician reviewers.
    End point type
    Primary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -2.458 (-2.681 to -2.234)
    -0.380 (-0.611 to -0.148)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in NPS at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.0001 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -2.078
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.399
         upper limit
    		 -1.757
    Notes
    [1] - For participants whose NPS data collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [2] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Primary: Change from baseline in bi-weekly mean nasal congestion score (NCS) at Week 52

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    End point title
    		 Change from baseline in bi-weekly mean nasal congestion score (NCS) at Week 52
    End point description
    The NCS is captured by one item in the NPSD (nasal polyps symptom diary) asking participants to rate the severity of their worst NC over the past 24 hours using the following response options: 0 – None; 1 – Mild; 2 – Moderate; 3 – Severe. Baseline will be the mean of daily responses from Day -13 to Day 0. Bi-weekly (14-day) mean NCS will be calculated if at least 8 days in each 14-day period has evaluable data; otherwise the bi-weekly mean is set to missing.
    End point type
    Primary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -1.743 (-1.864 to -1.622)
    -0.703 (-0.830 to -0.577)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in bi-weekly mean NCS at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.0001 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -1.039
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.214
         upper limit
    		 -0.865
    Notes
    [3] - For participants whose NCS data collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [4] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Change from baseline in bi-weekly mean loss of smell at Week 52

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    End point title
    		 Change from baseline in bi-weekly mean loss of smell at Week 52
    End point description
    Participant reported sense of smell will be evaluated as part of the NPSD. Loss of smell is captured by the DSS item (difficulty with sense of smell) in the NPSD asking participants to rate the severity of their worst difficulty with sense of smell over the past 24 hours using the following response options: 0 – None; 1 – Mild; 2 – Moderate; 3 – Severe. Baseline will be the mean of daily responses to the from Day -13 to Day 0. Bi-weekly (14-day) mean loss of smell will be calculated if at least 8 days in each 14-day period has evaluable data; otherwise the bi-weekly mean is set to missing.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -1.261 (-1.382 to -1.139)
    -0.255 (-0.378 to -0.133)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in bi-weekly mean loss of smell at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.0001 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -1.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.177
         upper limit
    		 -0.834
    Notes
    [5] - For participants whose loss of smell data collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [6] - The p-value is unadjusted, and is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Change from baseline in SinoNasal Outcome Test 22 (SNOT-22) at Week 52

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    End point title
    		 Change from baseline in SinoNasal Outcome Test 22 (SNOT-22) at Week 52
    End point description
    SinoNasal Outcome Test 22 scores are participant-reported and assess physical problems, functional limitations and emotional consequences of SinoNasal conditions. Patient-reported symptom severity and symptom impact over the past 2 weeks are captured via a 6-point scale (0-No Problem to 5-Problem as bad as it can be). The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes).
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -45.022 (-48.572 to -41.472)
    -17.580 (-21.189 to -13.971)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in SNOT-22 at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.0001 [8]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -27.441
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.512
         upper limit
    		 -22.37
    Notes
    [7] - For participants whose SNOT-22 total score collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [8] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Change from baseline in Lund Mackay score evaluated by CT at Week 52.

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    End point title
    		 Change from baseline in Lund Mackay score evaluated by CT at Week 52.
    End point description
    The Lund-Mackay score scoring system is used to provide a quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-Normal; 1-Partial Opacification; 2-Total Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The total score ranges from 0 to 24 (higher scores indicate poorer outcomes).
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -6.270 (-6.740 to -5.799)
    -0.569 (-1.046 to -0.093)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in LMK at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.0001 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -5.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.371
         upper limit
    		 -5.03
    Notes
    [9] - For participants whose LMK score collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [10] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Time to first nasal polyp surgery decision and/or systemic corticosteroids for nasal polyposis up to Week 52

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    End point title
    		 Time to first nasal polyp surgery decision and/or systemic corticosteroids for nasal polyposis up to Week 52
    End point description
    Surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g., polypectomy, endoscopic sinus surgery). Rescue treatment of NP is defined as requiring treatment with systemic corticosteroids (SCS) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids). Time to first NP surgery decision or SCS for NP = (date of the first NP surgery decision or start date of first SCS for NP use ‒ date of randomisation)+1
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Percentage
        number (confidence interval 95%)
    5.7 (1.3 to 15.0)
    31.4 (25.0 to 38.0)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null Hypothesis: Hazard ratio of time to first SCS for NP and/or surgery decision (tezepelumab/placebo) = 1
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [11]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 0.16
    Notes
    [11] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Time to first nasal polyp surgery decision up to Week 52

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    End point title
    		 Time to first nasal polyp surgery decision up to Week 52
    End point description
    Surgery is defined as any procedure involving instruments resulting in incision and removal of tissue (e.g., polypectomy, endoscopic sinus surgery). Time to first NP surgery decision = (date of the first NP surgery decision ‒ date of randomisation)+1
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Percentage
        number (confidence interval 95%)
    0.5 (0.0 to 2.5)
    22.0 (16.4 to 28.2)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null Hypothesis: Hazard ratio of time to first surgery decision (tezepelumab/placebo) = 1
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [12]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.09
    Notes
    [12] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Time to first systemic corticosteroids for nasal polyposis up to Week 52

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    End point title
    		 Time to first systemic corticosteroids for nasal polyposis up to Week 52
    End point description
    Rescue treatment of NP is defined as requiring treatment with systemic corticosteroids (SCS) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids). Time to first SCS for NP = (start date of first SCS for NP use ‒ date of randomisation)+1
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Percentage
        number (confidence interval 95%)
    5.2 (1.1 to 14.7)
    19.3 (14.1 to 25.1)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null Hypothesis: Hazard ratio of time to first SCS use for NP (tezepelumab/placebo) = 1
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [13]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.25
    Notes
    [13] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Change from baseline in bi-weekly mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52

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    End point title
    		 Change from baseline in bi-weekly mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52
    End point description
    The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and followup periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24hrs when responding to each question. Participants are asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, difficulty with sense of smell) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe). A total symptom score is calculated by taking the sum of the 8 equally weighted symptom items.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -10.388 (-11.174 to -9.601)
    -3.429 (-4.241 to -2.617)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in bi-weekly mean NPSD TSS at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    408
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 < 0.0001 [15]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -6.959
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.085
         upper limit
    		 -5.833
    Notes
    [14] - For participants whose bi-weekly mean NPSD TSS collected after NP surgery were replaced with the worst possible score (WPS). Data collected after SCS for NP were replaced with the worst post-baseline observation prior to the SCS for NP (WOCF). Missing data not due to intercurrent events were imputed using MI (MAR). Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [15] - The p-value is unadjusted and it is statistically significant at 0.01 level under multiple testing strategy.

    Secondary: Change from baseline in pre-bronchodilator forced expiratory volume (L) in 1 second at Week 52.

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    End point title
    		 Change from baseline in pre-bronchodilator forced expiratory volume (L) in 1 second at Week 52.
    End point description
    For participants with comorbid asthma and aspirin exacerbated respiratory disease (AERD)/nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD), difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) in the tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    122
    126
    Units: Liter
        arithmetic mean (confidence interval 95%)
    0.022 (-0.065 to 0.108)
    0.027 (-0.055 to 0.108)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in pre-BD FEV1 at 52 weeks (tezepelumab minus placebo) = 0
    Comparison groups
    Tezepelumab v Placebo
    Number of subjects included in analysis
    248
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    P-value
    		 = 0.9362 [17]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -0.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.121
         upper limit
    		 0.111
    Notes
    [16] - Observed pre-BD FEV1 data were used in the analysis regardless of NP surgery and SCS/biologic for NP. Missing data were imputed assuming MAR. Analysis was repeated on 100 imputed datasets, and results were combined using Rubin's formula.
    [17] - The p-value is unadjusted.

    Other pre-specified: Change from baseline over time in Nasal Polyp Score through Week 52.

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    End point title
    		 Change from baseline over time in Nasal Polyp Score through Week 52.
    End point description
    The total nasal polyp score (NPS) is the sum of the right and left nostril scores (maximum of 8), as evaluated by nasal endoscopy. Higher scores indicate greater symptom severity. The left and right score will be based on a central read with a scale from 0 to 4. Each nasal endoscopy is evaluated by two independent physician reviewers.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
    least squares mean (confidence interval 95%)
        Week 4
    -1.615 (-1.797 to -1.433)
    -0.255 (-0.434 to -0.077)
        Week 12
    -1.918 (-2.112 to -1.723)
    -0.376 (-0.569 to -0.182)
        Week 24
    -2.104 (-2.310 to -1.899)
    -0.314 (-0.522 to -0.106)
        Week 36
    -2.351 (-2.552 to -2.149)
    -0.287 (-0.493 to -0.082)
        Week 52
    -2.458 (-2.681 to -2.234)
    -0.380 (-0.611 to -0.148)
    No statistical analyses for this end point

    Other pre-specified: Proportion of participants with ≥1 point reduction in the Nasal Polyp Score at Week 52

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    End point title
    		 Proportion of participants with ≥1 point reduction in the Nasal Polyp Score at Week 52
    End point description
    The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy. A participant with ≥1 point reduction in NPS at Week 52 in the absence of SCS for NP, biologic for NP, or NP surgery at or prior to that time point was defined as a responder, otherwise the participant was defined as a non-responder.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Participants
    161
    64
    No statistical analyses for this end point

    Other pre-specified: Proportion of participants with ≥2 point reduction in the Nasal Polyp Score at Week 52

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    End point title
    		 Proportion of participants with ≥2 point reduction in the Nasal Polyp Score at Week 52
    End point description
    The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy. A participant with ≥2 point reduction in NPS at Week 52 in the absence of SCS for NP, biologic for NP, or NP surgery at or prior to that time point was defined as a responder, otherwise the participant was defined as a non-responder.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Participants
    129
    39
    No statistical analyses for this end point

    Other pre-specified: Change from baseline over time in bi-weekly mean Nasal Congestion Score evaluated by Nasal Polyposis Symptom Diary through Week 52.

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    End point title
    		 Change from baseline over time in bi-weekly mean Nasal Congestion Score evaluated by Nasal Polyposis Symptom Diary through Week 52.
    End point description
    The NCS is captured by one item in the NPSD (nasal polyps symptom diary) asking participants to rate the severity of their worst NC over the past 24 hours using the following response options: 0 – None; 1 – Mild; 2 – Moderate; 3 – Severe. Baseline will be the mean of daily responses from Day -13 to Day 0. Bi-weekly (14-day) mean NCS will be calculated if at least 8 days in each 14-day period has evaluable data; otherwise the bi-weekly mean is set to missing.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
    least squares mean (confidence interval 95%)
        Week 2
    -0.379 (-0.438 to -0.319)
    -0.192 (-0.251 to -0.133)
        Week 4
    -0.779 (-0.868 to -0.691)
    -0.322 (-0.411 to -0.234)
        Week 8
    -1.134 (-1.236 to -1.032)
    -0.451 (-0.553 to -0.349)
        Week 12
    -1.270 (-1.376 to -1.164)
    -0.607 (-0.714 to -0.500)
        Week 24
    -1.515 (-1.628 to -1.402)
    -0.703 (-0.818 to -0.588)
        Week 36
    -1.629 (-1.748 to -1.509)
    -0.726 (-0.850 to -0.601)
        Week 48
    -1.735 (-1.856 to -1.613)
    -0.721 (-0.847 to -0.594)
        Week 52
    -1.743 (-1.864 to -1.622)
    -0.703 (-0.830 to -0.577)
    No statistical analyses for this end point

    Other pre-specified: Change from baseline in loss of smell evaluated by University of Pennsylvania Smell Identification Test (UPSIT) at Week 52.

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    End point title
    		 Change from baseline in loss of smell evaluated by University of Pennsylvania Smell Identification Test (UPSIT) at Week 52.
    End point description
    The University of Pennsylvania Smell Identification Test is a quantitative test of olfactory function which uses microencapsulated odorants that are released by scratching standardized odour-impregnated test booklets. Scores are based on number of correctly identified odours (score range 0-40, lower scores indicate poorer outcomes).
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    9.310 (8.147 to 10.474)
    -0.192 (-1.378 to 0.993)
    No statistical analyses for this end point

    Other pre-specified: Change from baseline in Modified Lund Mackay score evaluated by CT at Week 52.

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    End point title
    		 Change from baseline in Modified Lund Mackay score evaluated by CT at Week 52.
    End point description
    The Modified Lund-Mackay score scoring system is used to provide a semi-quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-0% Opacification; 1-1-25% Opacification; 2-26-50% Opacification; 3-51-75% Opacification; 4-76-99% Opacification; 5-100% Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The maximum total Modified Lund Mackay score is 50, 54 when including the Osteomeatal complex score.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -17.520 (-18.708 to -16.332)
    -1.106 (-2.291 to 0.078)
    No statistical analyses for this end point

    Other pre-specified: Change from baseline in sinus severity score by quantitative CT assessment at Week 52

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    End point title
    		 Change from baseline in sinus severity score by quantitative CT assessment at Week 52
    End point description
    Quantitative assessment of sinus CT image data were used to derive an objective measure of sinus disease burden called sinus severity score. The sinus severity score is defined as: (sinus mucosal volume)/(sinus mucosal volume + sinus air volume)×100%.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
        least squares mean (confidence interval 95%)
    -32.754 (-35.047 to -30.461)
    -1.978 (-4.267 to 0.310)
    No statistical analyses for this end point

    Other pre-specified: Exposure of systemic corticosteroids over 52 Weeks

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    End point title
    		 Exposure of systemic corticosteroids over 52 Weeks
    End point description
    The number of courses of SCS for NP per year was analysed using a negative binomial model. The response variable was the number of courses of SCS for NP received by a participant over the planned treatment period. The model included treatment group, baseline co-morbid asthma/AERD/NSAID-ERD status, prior NP surgery status, and region as factors. The logarithm of the time at risk (in years) was used as an offset variable, to adjust different follow-up times. Time during a course was not included in the calculation of time at risk.
    End point type
    Other pre-specified
    End point timeframe
    Over 52 weeks
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Number of Courses
    9
    59
    No statistical analyses for this end point

    Other pre-specified: Change from baseline by domain of the Nasal Polyposis Symptom Diary through Week 52

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    End point title
    		 Change from baseline by domain of the Nasal Polyposis Symptom Diary through Week 52
    End point description
    The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and follow-up periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24 hours when responding to each question. Participants are asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, and difficulty with sense of smell) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe).
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
    least squares mean (confidence interval 95%)
        Nasal Blockage Week 2
    -0.359 (-0.416 to -0.301)
    -0.170 (-0.227 to -0.112)
        Nasal Blockage Week 4
    -0.744 (-0.831 to -0.656)
    -0.298 (-0.385 to -0.211)
        Nasal Blockage Week 8
    -1.122 (-1.225 to -1.018)
    -0.423 (-0.527 to -0.320)
        Nasal Blockage Week 12
    -1.259 (-1.367 to -1.152)
    -0.555 (-0.663 to -0.447)
        Nasal Blockage Week 24
    -1.502 (-1.617 to -1.387)
    -0.678 (-0.795 to -0.561)
        Nasal Blockage Week 36
    -1.628 (-1.750 to -1.506)
    -0.703 (-0.830 to -0.576)
        Nasal Blockage Week 48
    -1.697 (-1.821 to -1.573)
    -0.722 (-0.850 to -0.594)
        Nasal Blockage Week 52
    -1.759 (-1.882 to -1.636)
    -0.697 (-0.825 to -0.569)
        Nasal Congestion Week 2
    -0.379 (-0.438 to -0.319)
    -0.192 (-0.251 to -0.133)
        Nasal Congestion Week 4
    -0.779 (-0.868 to -0.691)
    -0.322 (-0.411 to -0.234)
        Nasal Congestion Week 8
    -1.134 (-1.236 to -1.032)
    -0.451 (-0.553 to -0.349)
        Nasal Congestion Week 12
    -1.270 (-1.376 to -1.164)
    -0.607 (-0.714 to -0.500)
        Nasal Congestion Week 24
    -1.515 (-1.628 to -1.402)
    -0.703 (-0.818 to -0.588)
        Nasal Congestion Week 36
    -1.629 (-1.748 to -1.509)
    -0.726 (-0.850 to -0.601)
        Nasal Congestion Week 48
    -1.735 (-1.856 to -1.613)
    -0.721 (-0.847 to -0.594)
        Nasal Congestion Week 52
    -1.743 (-1.864 to -1.622)
    -0.703 (-0.830 to -0.577)
        Runny Nose Week 2
    -0.347 (-0.407 to -0.288)
    -0.164 (-0.224 to -0.105)
        Runny Nose Week 4
    -0.676 (-0.757 to -0.595)
    -0.239 (-0.320 to -0.158)
        Runny Nose Week 8
    -0.966 (-1.056 to -0.875)
    -0.360 (-0.450 to -0.270)
        Runny Nose Week 12
    -1.075 (-1.173 to -0.976)
    -0.467 (-0.566 to -0.369)
        Runny Nose Week 24
    -1.258 (-1.363 to -1.153)
    -0.464 (-0.571 to -0.358)
        Runny Nose Week 36
    -1.353 (-1.466 to -1.240)
    -0.467 (-0.583 to -0.351)
        Runny Nose Week 48
    -1.448 (-1.561 to -1.336)
    -0.410 (-0.528 to -0.292)
        Runny Nose Week 52
    -1.429 (-1.545 to -1.313)
    -0.400 (-0.523 to -0.277)
        Postnasal Drip Week 2
    -0.252 (-0.310 to -0.195)
    -0.153 (-0.210 to -0.096)
        Postnasal Drip Week 4
    -0.552 (-0.633 to -0.472)
    -0.230 (-0.310 to -0.150)
        Postnasal Drip Week 8
    -0.806 (-0.898 to -0.715)
    -0.336 (-0.428 to -0.244)
        Postnasal Drip Week 12
    -0.916 (-1.015 to -0.816)
    -0.388 (-0.488 to -0.288)
        Postnasal Drip Week 24
    -1.084 (-1.194 to -0.974)
    -0.418 (-0.529 to -0.306)
        Postnasal Drip Week 36
    -1.175 (-1.290 to -1.061)
    -0.441 (-0.559 to -0.322)
        Postnasal Drip Week 48
    -1.189 (-1.307 to -1.071)
    -0.376 (-0.498 to -0.253)
        Postnasal Drip Week 52
    -1.177 (-1.294 to -1.060)
    -0.348 (-0.471 to -0.225)
        Headache Week 2
    -0.259 (-0.318 to -0.199)
    -0.185 (-0.245 to -0.126)
        Headache Week 4
    -0.414 (-0.489 to -0.340)
    -0.294 (-0.369 to -0.220)
        Headache Week 8
    -0.673 (-0.753 to -0.594)
    -0.382 (-0.461 to -0.303)
        Headache Week 12
    -0.753 (-0.842 to -0.665)
    -0.439 (-0.528 to -0.350)
        Headache Week 24
    -0.870 (-0.970 to -0.771)
    -0.470 (-0.571 to -0.369)
        Headache Week 36
    -0.928 (-1.034 to -0.821)
    -0.387 (-0.496 to -0.278)
        Headache Week 48
    -0.962 (-1.075 to -0.849)
    -0.361 (-0.476 to -0.245)
        Headache Week 52
    -0.941 (-1.056 to -0.825)
    -0.341 (-0.459 to -0.222)
        Facial Pain Week 2
    -0.250 (-0.310 to -0.190)
    -0.171 (-0.231 to -0.111)
        Facial Pain Week 4
    -0.438 (-0.514 to -0.363)
    -0.276 (-0.352 to -0.201)
        Facial Pain Week 8
    -0.723 (-0.806 to -0.640)
    -0.368 (-0.450 to -0.285)
        Facial Pain Week 12
    -0.801 (-0.888 to -0.713)
    -0.438 (-0.526 to -0.350)
        Facial Pain Week 24
    -0.957 (-1.056 to -0.858)
    -0.494 (-0.594 to -0.393)
        Facial Pain Week 36
    -1.000 (-1.106 to -0.893)
    -0.396 (-0.506 to -0.286)
        Facial Pain Week 48
    -1.010 (-1.125 to -0.895)
    -0.358 (-0.476 to -0.239)
        Facial Pain Week 52
    -1.002 (-1.118 to -0.886)
    -0.316 (-0.436 to -0.197)
        Facial Pressure Week 2
    -0.276 (-0.338 to -0.215)
    -0.170 (-0.232 to -0.109)
        Facial Pressure Week 4
    -0.509 (-0.587 to -0.431)
    -0.277 (-0.355 to -0.199)
        Facial Pressure Week 8
    -0.778 (-0.866 to -0.689)
    -0.373 (-0.461 to -0.284)
        Facial Pressure Week 12
    -0.840 (-0.929 to -0.750)
    -0.460 (-0.549 to -0.370)
        Facial Pressure Week 24
    -0.987 (-1.087 to -0.887)
    -0.501 (-0.603 to -0.400)
        Facial Pressure Week 36
    -1.039 (-1.148 to -0.930)
    -0.400 (-0.512 to -0.288)
        Facial Pressure Week 48
    -1.093 (-1.210 to -0.975)
    -0.379 (-0.499 to -0.258)
        Facial Pressure Week 52
    -1.081 (-1.200 to -0.962)
    -0.342 (-0.464 to -0.220)
        Difficulty with Sense of Smell Week 2
    -0.126 (-0.164 to -0.088)
    -0.037 (-0.074 to 0.001)
        Difficulty with Sense of Smell Week 4
    -0.416 (-0.483 to -0.348)
    -0.053 (-0.120 to 0.014)
        Difficulty with Sense of Smell Week 8
    -0.804 (-0.897 to -0.711)
    -0.107 (-0.200 to -0.015)
        Difficulty with Sense of Smell Week 12
    -0.909 (-1.015 to -0.804)
    -0.208 (-0.313 to -0.103)
        Difficulty with Sense of Smell Week 24
    -1.078 (-1.195 to -0.961)
    -0.275 (-0.392 to -0.158)
        Difficulty with Sense of Smell Week 36
    -1.101 (-1.221 to -0.980)
    -0.300 (-0.422 to -0.177)
        Difficulty with Sense of Smell Week 48
    -1.242 (-1.364 to -1.121)
    -0.289 (-0.413 to -0.166)
        Difficulty with Sense of Smell Week 52
    -1.261 (-1.382 to -1.139)
    -0.255 (-0.378 to -0.133)
        Difficulty with Sleeping Week 2
    -0.340 (-0.399 to -0.281)
    -0.188 (-0.247 to -0.129)
        Difficulty with Sleeping Week 4
    -0.655 (-0.738 to -0.572)
    -0.284 (-0.367 to -0.202)
        Difficulty with Sleeping Week 8
    -0.994 (-1.084 to -0.904)
    -0.454 (-0.544 to -0.364)
        Difficulty with Sleeping Week 12
    -1.081 (-1.177 to -0.984)
    -0.495 (-0.591 to -0.398)
        Difficulty with Sleeping Week 24
    -1.262 (-1.365 to -1.159)
    -0.516 (-0.621 to -0.411)
        Difficulty with Sleeping Week 36
    -1.307 (-1.420 to -1.194)
    -0.520 (-0.637 to -0.403)
        Difficulty with Sleeping Week 48
    -1.307 (-1.427 to -1.188)
    -0.469 (-0.595 to -0.342)
        Difficulty with Sleeping Week 52
    -1.317 (-1.436 to -1.197)
    -0.454 (-0.580 to -0.327)
        Difficulty with Daily Activities week 2
    -0.282 (-0.340 to -0.225)
    -0.183 (-0.240 to -0.126)
        Difficulty with Daily Activities week 4
    -0.504 (-0.582 to -0.425)
    -0.294 (-0.372 to -0.216)
        Difficulty with Daily Activities week 8
    -0.836 (-0.926 to -0.747)
    -0.408 (-0.497 to -0.319)
        Difficulty with Daily Activities week 12
    -0.948 (-1.043 to -0.853)
    -0.469 (-0.564 to -0.374)
        Difficulty with Daily Activities week 24
    -1.135 (-1.242 to -1.028)
    -0.520 (-0.628 to -0.412)
        Difficulty with Daily Activities week 36
    -1.201 (-1.316 to -1.085)
    -0.509 (-0.629 to -0.389)
        Difficulty with Daily Activities week 48
    -1.213 (-1.334 to -1.091)
    -0.440 (-0.568 to -0.313)
        Difficulty with Daily Activities week 52
    -1.212 (-1.334 to -1.090)
    -0.414 (-0.542 to -0.285)
    No statistical analyses for this end point

    Other pre-specified: Change from baseline in Nasal Peak Inspiratory Flow through Week 52.

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    End point title
    		 Change from baseline in Nasal Peak Inspiratory Flow through Week 52.
    End point description
    Nasal peak inspiratory flow evaluation represents a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute.
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    205
    Units: Score
    least squares mean (confidence interval 95%)
        Week 12
    21.860 (10.888 to 32.831)
    -1.695 (-12.313 to 8.923)
        Week 24
    29.437 (17.500 to 41.373)
    6.258 (-5.563 to 18.080)
        Week 36
    11.228 (0.875 to 21.581)
    -4.941 (-15.570 to 5.687)
        Week 52
    22.551 (11.467 to 33.635)
    0.489 (-10.973 to 11.952)
    No statistical analyses for this end point

    Other pre-specified: Change from baseline in Asthma Control Questionnaire-6 at Week 52.

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    End point title
    		 Change from baseline in Asthma Control Questionnaire-6 at Week 52.
    End point description
    The Asthma Control Questionnaire is an assessment of asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short acting beta-agonist use). Participants are asked to recall their level of asthma control during the previous week by responding to one bronchodilator use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    122
    126
    Units: Score
        least squares mean (confidence interval 95%)
    -1.203 (-1.334 to -1.072)
    -0.815 (-0.967 to -0.663)
    No statistical analyses for this end point

    Other pre-specified: Tezepelumab Pharmacokinetics

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    End point title
    		 Tezepelumab Pharmacokinetics
    End point description
    Serum concentrations of tezepelumab through Week 64. Geometric mean calculated using log transformed data.
    End point type
    Other pre-specified
    End point timeframe
    Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, and Week 64
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    203
    0 [18]
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Week 4
    12.165 ( 35.9 )
    ( )
        Week 12
    21.496 ( 40.8 )
    ( )
        Week 24
    23.994 ( 43.0 )
    ( )
        Week 36
    25.237 ( 45.4 )
    ( )
        Week 52
    24.352 ( 43.7 )
    ( )
        Week 64
    2.449 ( 103.1 )
    ( )
    Notes
    [18] - Serum concentrations of Tezepelumab is not available for placebo.
    No statistical analyses for this end point

    Other pre-specified: Immunogenicity of tezepelumab for Non-China subjects

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    End point title
    		 Immunogenicity of tezepelumab for Non-China subjects
    End point description
    Anti-drug antibodies (ADA) responses at baseline and post-baseline. ADA prevalence was defined as patients who are ADA positive at any time including baseline. Persistently positive was defined as having at least two post-baseline ADA positive measurements (with ≥16 weeks between first and last positive) or an ADA positive result at the last available post-baseline assessment. Transiently positive was defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Treatment boosted ADA was defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment. Treatment emergent ADA (ADA incidence) was defined as the sum of treatment induced ADA and treatment boosted ADA.
    End point type
    Other pre-specified
    End point timeframe
    Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, and Week 64
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    174
    171
    Units: Participants
        ADA prevalence
    10
    19
        ADA positive at baseline only
    2
    1
        Treatment-induced ADA positive
    6
    12
        Treatment-boosted ADA positive
    0
    0
        Treatment emergent ADA (ADA incidence)
    6
    12
        Baseline and one post-baseline ADA positive
    2
    4
        ADA persistently positive
    4
    11
        ADA transiently positive
    4
    7
        TE-ADA+ with max. titre > median of max. titres
    1
    2
        ADA positive at baseline
    4
    2
        Any post-baseline ADA positive
    8
    18
        nAb positive at baseline and/or post-baseline
    2
    2
        Treatment-induced nAb positive (nAb incidence)
    1
    2
    No statistical analyses for this end point

    Other pre-specified: Immunogenicity of tezepelumab for China subjects

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    End point title
    		 Immunogenicity of tezepelumab for China subjects
    End point description
    Anti-drug antibodies (ADA) responses at baseline and post-baseline. ADA prevalence was defined as patients who are ADA positive at any time including baseline. Persistently positive was defined as having at least two post-baseline ADA positive measurements (with ≥16 weeks between first and last positive) or an ADA positive result at the last available post-baseline assessment. Transiently positive was defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Treatment boosted ADA was defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment. Treatment emergent ADA (ADA incidence) was defined as the sum of treatment induced ADA and treatment boosted ADA.
    End point type
    Other pre-specified
    End point timeframe
    Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, and Week 64
    End point values
    		 Tezepelumab Placebo
    Number of subjects analysed
    29
    34
    Units: Participants
        ADA prevalence
    3
    4
        ADA positive at baseline only
    1
    0
        Treatment-induced ADA positive
    2
    3
        Treatment-boosted ADA positive
    0
    0
        Treatment emergent ADA (ADA incidence)
    2
    3
        Baseline and one post-baseline ADA positive
    0
    1
        ADA persistently positive
    1
    2
        ADA transiently positive
    1
    2
        TE-ADA+ with max. titre > median of max. titres
    1
    0
        ADA positive at baseline
    1
    1
        Any post-baseline ADA positive
    2
    4
        nAb positive at baseline and/or post-baseline
    1
    0
        Treatment-induced nAb positive (nAb incidence)
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until end of study up to week 76.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching Placebo injection delivered subcutaneously every 4 weeks

    Reporting group title
    Tezepelumab
    Reporting group description
    		 210 mg tezepelumab injection delivered subcutaneously every 4 weeks

    Serious adverse events
    		 Placebo Tezepelumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 205 (6.83%)
    11 / 203 (5.42%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive lobular breast carcinoma
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopericarditis
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Basal ganglia stroke
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Epiretinal membrane
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 205 (0.98%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Graves' disease
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 205 (0.49%)
    0 / 203 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 205 (0.00%)
    1 / 203 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Tezepelumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    119 / 205 (58.05%)
    119 / 203 (58.62%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 205 (7.80%)
    19 / 203 (9.36%)
         occurrences all number
    22
    30
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    12 / 205 (5.85%)
    1 / 203 (0.49%)
         occurrences all number
    15
    1
    Chronic rhinosinusitis with nasal polyps
         subjects affected / exposed
    56 / 205 (27.32%)
    16 / 203 (7.88%)
         occurrences all number
    104
    26
    Epistaxis
         subjects affected / exposed
    7 / 205 (3.41%)
    14 / 203 (6.90%)
         occurrences all number
    8
    15
    Infections and infestations
    COVID-19
         subjects affected / exposed
    44 / 205 (21.46%)
    55 / 203 (27.09%)
         occurrences all number
    47
    58
    Nasopharyngitis
         subjects affected / exposed
    23 / 205 (11.22%)
    45 / 203 (22.17%)
         occurrences all number
    42
    63
    Pharyngitis
         subjects affected / exposed
    1 / 205 (0.49%)
    11 / 203 (5.42%)
         occurrences all number
    1
    13
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 205 (6.34%)
    23 / 203 (11.33%)
         occurrences all number
    16
    26

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Jan 2022
    1. Added “bi-weekly mean” for NCS, loss of smell, and NPSD TSS to ensure correct evaluation of these endpoints from baseline over time. 2. Overall benefits-risk conclusion was updated to align with IB Edition 5.0 (dated 21 October 2021). 3. Exclusion Criterion for patients with a history of cancer was updated in order to align with program-level safety documentation regarding patients with a history of cancer. 4. Inclusion Criterion 15 “NCS ≥ 2 at Visit 3” removed. Inclusion 15a added to replace previous Inclusion Criterion 15. Inclusion 15a added: “At randomisation visit (Visit 3), a bi-weekly mean NCS ≥ 2 (baseline bi-weekly mean score collected from study Day -13 to study Day 0).”
    17 Oct 2022
    Update of key secondary objectives and corresponding endpoints: (1) ‘Time to surgery and/or SCS for NP up to Week 52’ updated to ‘Time to surgery decision and/or SCS for NP up to Week 52’. (2) ‘Time to NP surgery up to Week 52’ updated to ‘Time to NP surgery decision up to Week 52’. Adverse events of special interest updated to include ‘serious cardiac events’ and ‘including opportunistic infections’ added to AESI of serious infections. New category added to risk assessment table: “Important potential risks” including serious infections, malignancies and serious cardiac events. Previous category of “Potential risks of clinical significance” changed to “Potential risks” and text of risk of serious infections, serious hypersensitivity reactions, and COVID-19 updated.
    17 Jan 2024
    Two key secondary objectives ‘resolution/near complete resolution of nasal polyps’, and ‘resolution/near complete resolution of nasal polyps and NPSD TSS responses’ were moved to exploratory objectives. Estimand for US FDA and multiplicity testing procedure for secondary endpoints were modified to align with FDA guidance.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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