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Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)

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ClinicalTrials.gov Identifier: NCT03347279
Recruitment Status : Completed
First Posted : November 20, 2017
Results First Posted : November 26, 2021
Last Update Posted : November 26, 2021
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Experimental: Tezepelumab
Other: Placebo
Enrollment 1061
Recruitment Details A total of 1061 subjects were randomised at 231 centres in 17 countries to receive treatment with tezepelumab 210mg Q4W or placebo,
Pre-assignment Details Of the 1061 randomised, 1059 (99.8%) subjects received treatment. 82 (7.7%) of the subjects randomised and treated were adolescents.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description Tezepelumab administered every 4 weeks subcutaneously Placebo administered subcutaneously
Period Title: Overall Study
Started 529 532
Received Treatment 528 531
Completed 513 509
Not Completed 16 23
Reason Not Completed
Withdrawal by Subject             8             15
Death             0             2
Lost to Follow-up             5             2
Did not receive treatment / Non-compliance with protocol / did not complete safety follow-up visits             3             4
Arm/Group Title Tezepelumab 210mg Q4W Placebo Total
Hide Arm/Group Description Tezepelumab administered every 4 weeks subcutaneously Placebo administered subcutaneously Total of all reporting groups
Overall Number of Baseline Participants 528 531 1059
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 528 participants 531 participants 1059 participants
<=18 years
41
   7.8%
41
   7.7%
82
   7.7%
Between 18 and 65 years
391
  74.1%
416
  78.3%
807
  76.2%
>=65 years
96
  18.2%
74
  13.9%
170
  16.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 528 participants 531 participants 1059 participants
49.9  (16.3) 49.0  (15.9) 49.5  (16.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 528 participants 531 participants 1059 participants
Female
335
  63.4%
337
  63.5%
672
  63.5%
Male
193
  36.6%
194
  36.5%
387
  36.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 528 participants 531 participants 1059 participants
White 332 327 659
Black of African American 30 31 61
Asian 146 149 295
Native Hawaiian or Other Pacific Islander 1 0 1
American Indian or Alaska Native 0 1 1
Other 19 23 42
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 528 participants 531 participants 1059 participants
Hispanic or Latino 83 81 164
Not Hispanic or Latino 445 450 895
1.Primary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma
Hide Description The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set)
Time Frame From randomisation to Study Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
0.93
(0.80 to 1.07)
2.10
(1.84 to 2.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative Binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.37 to 0.53
Estimation Comments [Not Specified]
2.Primary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL
Hide Description The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils < 300 cells/uL
Time Frame From randomisation to Study Week 52.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 309 309
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
1.02
(0.84 to 1.23)
1.73
(1.46 to 2.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative Binomial
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.46 to 0.75
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint)
Hide Description Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 471 453
Least Squares Mean (Standard Error)
Unit of Measure: Litre
0.23  (0.018) 0.10  (0.018)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.08 to 0.18
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint)
Hide Description Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 480 467
Least Squares Mean (Standard Error)
Unit of Measure: Scale of score
1.48  (0.049) 1.14  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.2 to 0.47
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint)
Hide Description Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 485 472
Least Squares Mean (Standard Error)
Unit of Measure: Scale of score
-1.53  (0.045) -1.20  (0.046)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.46 to -0.2
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint)
Hide Description Mean change from baseline at Week 52 in Asthma Symptom Diary. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4, where 0 indicates no asthma symptoms.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed is the number of subjects with a weekly mean at Week 52. All subjects from the Full Analysis Set with at least one change from baseline weekly mean at any post-baseline week contributes to the analyses.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 374 355
Least Squares Mean (Standard Error)
Unit of Measure: Scale of score
-0.70  (0.027) -0.59  (0.027)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tezepelumab 210mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.19 to -0.04
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Time to First Asthma Exacerbation
Hide Description Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Measure Type: Count of Participants
Unit of Measure: Participants
231
  43.8%
319
  60.1%
8.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb)
Hide Description Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 440 426
Least Squares Mean (Standard Error)
Unit of Measure: ppb
-17.29  (1.156) -3.46  (1.165)
9.Secondary Outcome
Title Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52
Hide Description Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of daytime inhaler puffs + 2 x [number of day nebulizer times]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 439 428
Least Squares Mean (Standard Error)
Unit of Measure: weekly mean rescue medication use
-2.53  (0.137) -2.36  (0.137)
10.Secondary Outcome
Title Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The work productivity loss is only applicable to subjects who were employed, which is a subset of the study population.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 185 177
Mean (Standard Deviation)
Unit of Measure: Percentage of work productivity loss
-20.16  (30.31) -16.58  (29.46)
11.Secondary Outcome
Title Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Class productivity loss is derived by sum of percentage of missed class hours due to asthma and product of percentage of actual hours in class times degree of asthma affecting productivity while in class. Percentage of missed hours in class due to asthma is calculated by number of hours in class missed due to asthma divided by total number of hours in class missed plus number of hours actually in class.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The class productivity loss is only applicable to subjects attending school, which is a subset of the study population.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 15 19
Mean (Standard Deviation)
Unit of Measure: Percentage of class productivity loss
-14.03  (33.00) -24.72  (26.48)
12.Secondary Outcome
Title Activity Impairment at Week 52
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 401 393
Mean (Standard Deviation)
Unit of Measure: Percentage of activity impairment
-20.0  (28.6) -17.9  (27.1)
13.Secondary Outcome
Title Pharmacokinetics of Tezepelumab
Hide Description Mean serum trough PK concentrations taken pre-dose at each visit
Time Frame Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Number of subjects who received at least one dose of IP. Number analysed at each timepoint is a subset of this based on subjects who had sample results available at that timepoint. The placebo arm is not applicable since it is not the experimental product.
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug/mL
Baseline Number Analyzed 524 participants 0 participants
0
(0%)
Week 4 Number Analyzed 514 participants 0 participants
10.1573
(74.51%)
Week 12 Number Analyzed 491 participants 0 participants
18.7396
(48.53%)
Week 24 Number Analyzed 461 participants 0 participants
20.1924
(51.77%)
Week 36 Number Analyzed 464 participants 0 participants
19.5246
(55.58%)
Week 52 Number Analyzed 452 participants 0 participants
19.8894
(70.04%)
Week 64 Number Analyzed 72 participants 0 participants
1.7675
(171.86%)
14.Secondary Outcome
Title Mean Change From Baseline at Week 52 in EQ-5D-5L VAS
Hide Description Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time Frame At Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 448 435
Least Squares Mean (Standard Error)
Unit of Measure: scale of score
14.64  (0.708) 11.86  (0.712)
15.Secondary Outcome
Title Clinicians Global Impression of Change at Week 52
Hide Description CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse)
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 483 477
Measure Type: Count of Participants
Unit of Measure: Participants
Very much improved
96
  19.9%
60
  12.6%
Much improved
199
  41.2%
132
  27.7%
Minimally improved
98
  20.3%
131
  27.5%
No change
77
  15.9%
130
  27.3%
Minimally worse
11
   2.3%
19
   4.0%
Much worse
2
   0.4%
4
   0.8%
Very much worse
0
   0.0%
1
   0.2%
16.Secondary Outcome
Title Patients Global Impression of Change at Week 52
Hide Description PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse).
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 479 466
Measure Type: Count of Participants
Unit of Measure: Participants
Very much improved
255
  53.2%
182
  39.1%
Much Improved
103
  21.5%
94
  20.2%
Minimally improved
71
  14.8%
76
  16.3%
No change
39
   8.1%
99
  21.2%
Minimally worse
6
   1.3%
8
   1.7%
Much worse
4
   0.8%
6
   1.3%
Very much worse
1
   0.2%
1
   0.2%
17.Secondary Outcome
Title Patients Global Impression of Severity at Week 52
Hide Description PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms
Time Frame At Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 479 466
Measure Type: Count of Participants
Unit of Measure: Participants
No symptoms
118
  24.6%
78
  16.7%
Very mild symptoms
138
  28.8%
128
  27.5%
Mild symptoms
110
  23.0%
128
  27.5%
Moderate symptoms
99
  20.7%
111
  23.8%
Severe symptoms
14
   2.9%
19
   4.1%
Very severe symptoms
0
   0.0%
2
   0.4%
18.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL)
Hide Description Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 458 451
Least Squares Mean (Standard Error)
Unit of Measure: cells/uL
-170.02  (9.222) -40.15  (9.254)
19.Secondary Outcome
Title Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL)
Hide Description Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 482 471
Least Squares Mean (Standard Error)
Unit of Measure: IU/mL
-164.38  (34.414) 43.61  (34.542)
20.Secondary Outcome
Title Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks
Hide Description Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Measure Type: Number
Unit of Measure: Participants
Hospitalisation 17 37
Emergency Room visit 23 50
Unscheduled visit to specialist 187 231
Home visit 9 10
Telephone call 101 133
Ambulance transport 4 12
21.Secondary Outcome
Title Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)
Hide Description Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 414 391
Least Squares Mean (Standard Error)
Unit of Measure: L/min
34.57  (3.051) 18.01  (3.074)
22.Secondary Outcome
Title Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)
Hide Description Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 405 390
Least Squares Mean (Standard Error)
Unit of Measure: L/min
23.87  (3.075) 9.01  (3.094)
23.Secondary Outcome
Title Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52
Hide Description Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 418 395
Least Squares Mean (Standard Error)
Unit of Measure: percentage of nights with awakenings
-33.51  (1.381) -30.22  (1.387)
24.Secondary Outcome
Title Immunogenecity of Tezepelumab
Hide Description Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.
Time Frame Baseline, and from time of first dose at Week 0 to end of study at Week 64.
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 527 530
Measure Type: Number
Unit of Measure: Participants
ADA positive at baseline and/or post-baseline 26 44
Any baseline ADA positive 17 25
Only baseline ADA positive 14 8
Any post-baseline ADA positive 12 36
Both baseline and >= 1 post-baseline ADA positive 3 17
Treatment induced ADA positive 9 18
Treatment boosted ADA positive 1 2
Treatment emergent ADA positive 10 20
ADA persistently positive 4 18
ADA transiently positive 8 18
25.Secondary Outcome
Title Proportion of Subjects Who Had no Asthma Exacerbations
Hide Description The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.
Time Frame From randomisation to Study Week 52
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Measure Type: Number
Unit of Measure: Percentage
54.2 38.6
26.Secondary Outcome
Title Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation
Hide Description The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF)
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
0.06
(0.04 to 0.09)
0.28
(0.20 to 0.39)
27.Secondary Outcome
Title Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation
Hide Description Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation.
Time Frame From randomisation to Study Week 52
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Measure Type: Number
Unit of Measure: Percentage
4.7 12.2
28.Secondary Outcome
Title Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation
Hide Description The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Measure Type: Number
Unit of Measure: Percentage
92.4 85.1
29.Other Pre-specified Outcome
Title Annual Asthma Exacerbation Rate Associated With Hospitalisations
Hide Description The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
0.03
(0.01 to 0.06)
0.19
(0.12 to 0.30)
30.Other Pre-specified Outcome
Title Annual Asthma Exacerbation Rate Using Adjudicated Data
Hide Description The annualized exacerbation rate is based on exacerbations as defined for the primary endpoint, but any hospitalisation and ER visits which are adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
0.94
(0.81 to 1.09)
2.14
(1.88 to 2.44)
31.Other Pre-specified Outcome
Title Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data
Hide Description The annualized exacerbation rate is based on exacerbations associated with hospitalisations or ER visits, where hospitalisation and ER visits adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.
Time Frame From randomisation to Study Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description:
Tezepelumab administered every 4 weeks subcutaneously
Placebo administered subcutaneously
Overall Number of Participants Analyzed 528 531
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events per year
0.08
(0.05 to 0.12)
0.31
(0.22 to 0.42)
Time Frame From first dose of study drug until end of study at Week 64.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tezepelumab 210mg Q4W Placebo
Hide Arm/Group Description Tezepelumab administered every 4 weeks subcutaneously Placebo administered subcutaneously
All-Cause Mortality
Tezepelumab 210mg Q4W Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/528 (0.00%)      2/531 (0.38%)    
Hide Serious Adverse Events
Tezepelumab 210mg Q4W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   52/528 (9.85%)      73/531 (13.75%)    
Cardiac disorders     
Aortic valve stenosis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Cardiac failure  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Cardiac failure congestive  1  2/528 (0.38%)  2 0/531 (0.00%)  0
Coronary artery disease  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Coronary artery occlusion  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Ventricular extrasystoles  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Congenital, familial and genetic disorders     
Hypertrophic cardiomyopathy  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Ear and labyrinth disorders     
Vertigo positional  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Eye disorders     
Cataract  1  1/528 (0.19%)  2 1/531 (0.19%)  1
Uveitis  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Gastrointestinal disorders     
Colitis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Colitis ischaemic  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Diverticular perforation  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Inguinal hernia  1  0/528 (0.00%)  0 1/531 (0.19%)  2
Obstruction gastric  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Oesophageal achalasia  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pancreatitis acute  1  0/528 (0.00%)  0 1/531 (0.19%)  3
Pancreatitis necrotising  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Rectal haemorrhage  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Umbilical hernia  1  1/528 (0.19%)  1 1/531 (0.19%)  1
General disorders     
Death  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Non-cardiac chest pain  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis chronic  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Cholelithiasis  1  1/528 (0.19%)  1 1/531 (0.19%)  1
Immune system disorders     
Anaphylactic reaction  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Infections and infestations     
Anal abscess  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Atypical pneumonia  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Breast abscess  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Cellulitis  1  0/528 (0.00%)  0 2/531 (0.38%)  2
Diverticulitis  1  1/528 (0.19%)  1 1/531 (0.19%)  1
Gastroenteritis  1  0/528 (0.00%)  0 2/531 (0.38%)  2
Gastroenteritis salmonella  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Gastroenteritis viral  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Herpes zoster oticus  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Influenza  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Lower respiratory tract infection  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Lower respiratory tract infection bacterial  1  0/528 (0.00%)  0 2/531 (0.38%)  4
Lung abscess  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pneumonia bacterial  1  2/528 (0.38%)  2 2/531 (0.38%)  2
Pneumonia klebsiella  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pneumonia streptococcal  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pneumonia viral  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Upper respiratory tract infection  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Viral upper respiratory tract infection  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Covid-19  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Osteomyelitis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Pneumonia  1  1/528 (0.19%)  1 1/531 (0.19%)  1
Septic shock  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Injury, poisoning and procedural complications     
Hip fracture  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Incisional hernia  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Ligament rupture  1  2/528 (0.38%)  2 0/531 (0.00%)  0
Ligament sprain  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Lumbar vertebral fracture  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Radius fracture  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Road traffic accident  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Skin laceration  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Tendon rupture  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Tibia fracture  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Ulna fracture  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Head injury  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Investigations     
Blood creatine phosphokinase increased  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Diabetic ketoacidosis  1  0/528 (0.00%)  0 1/531 (0.19%)  2
Gout  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Type 1 diabetes mellitus  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Type 2 diabetes mellitus  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Musculoskeletal and connective tissue disorders     
Bone cyst  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Myositis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Osteoarthritis  1  1/528 (0.19%)  1 1/531 (0.19%)  1
Polyarthritis  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Spinal stenosis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Lumbar spinal stenosis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Muscle necrosis  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/528 (0.19%)  1 2/531 (0.38%)  2
Benign neoplasm of thyroid gland  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Colon adenoma  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Endometrial cancer  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Malignant melanoma in situ  1  2/528 (0.38%)  2 0/531 (0.00%)  0
Prostate cancer  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Squamous cell carcinoma  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Squamous cell carcinoma of the oral cavity  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Nervous system disorders     
Cubital tunnel syndrome  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Haemorrhagic stroke  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Idiopathic generalised epilepsy  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Migraine  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Myelopathy  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Transient ischaemic attack  1  1/528 (0.19%)  1 1/531 (0.19%)  2
Seizure  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  2/528 (0.38%)  2 0/531 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Ureterolithiasis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Reproductive system and breast disorders     
Ovarian cyst  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  14/528 (2.65%)  15 39/531 (7.34%)  81
Eosinophilic pneumonia  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Epistaxis  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Nasal polyps  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Pulmonary embolism  1  0/528 (0.00%)  0 1/531 (0.19%)  1
Skin and subcutaneous tissue disorders     
Dermatitis contact  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Vascular disorders     
Cyanosis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
Thrombosis  1  1/528 (0.19%)  1 0/531 (0.00%)  0
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Tezepelumab 210mg Q4W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   306/528 (57.95%)      331/531 (62.34%)    
General disorders     
Influenza like illness  1  19/528 (3.60%)  21 22/531 (4.14%)  26
Infections and infestations     
Bronchitis bacterial  1  24/528 (4.55%)  26 17/531 (3.20%)  20
Urinary tract infection  1  22/528 (4.17%)  33 22/531 (4.14%)  24
Viral upper respiratory tract infection  1  17/528 (3.22%)  21 13/531 (2.45%)  18
Bronchitis  1  25/528 (4.73%)  39 33/531 (6.21%)  36
Gastroenteritis  1  17/528 (3.22%)  18 14/531 (2.64%)  15
Nasopharyngitis  1  113/528 (21.40%)  172 114/531 (21.47%)  188
Pharyngitis  1  17/528 (3.22%)  18 15/531 (2.82%)  17
Rhinitis  1  14/528 (2.65%)  18 17/531 (3.20%)  37
Sinusitis  1  19/528 (3.60%)  22 40/531 (7.53%)  56
Upper respiratory tract infection  1  58/528 (10.98%)  94 88/531 (16.57%)  129
Musculoskeletal and connective tissue disorders     
Arthralgia  1  20/528 (3.79%)  25 13/531 (2.45%)  14
Back pain  1  21/528 (3.98%)  26 15/531 (2.82%)  16
Nervous system disorders     
Headache  1  43/528 (8.14%)  96 45/531 (8.47%)  68
Respiratory, thoracic and mediastinal disorders     
Asthma  1  14/528 (2.65%)  17 23/531 (4.33%)  25
Rhinitis allergic  1  16/528 (3.03%)  19 17/531 (3.20%)  25
Vascular disorders     
Hypertension  1  23/528 (4.36%)  27 22/531 (4.14%)  29
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Head
Organization: AstraZeneca
Phone: +1 302 885 1180
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03347279    
Other Study ID Numbers: D5180C00007
First Submitted: November 9, 2017
First Posted: November 20, 2017
Results First Submitted: September 7, 2021
Results First Posted: November 26, 2021
Last Update Posted: November 26, 2021