Trial Outcomes & Findings for Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NCT NCT03347279)

Last Updated: 2021-11-26

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1061 participants

Primary outcome timeframe

From randomisation to Study Week 52.

Results posted on

2021-11-26

Participant Flow

A total of 1061 subjects were randomised at 231 centres in 17 countries to receive treatment with tezepelumab 210mg Q4W or placebo,

Of the 1061 randomised, 1059 (99.8%) subjects received treatment. 82 (7.7%) of the subjects randomised and treated were adolescents.

Participant milestones

Participant milestones
Measure	Tezepelumab 210mg Q4W Tezepelumab administered every 4 weeks subcutaneously	Placebo Placebo administered subcutaneously
Overall Study STARTED	529	532
Overall Study Received Treatment	528	531
Overall Study COMPLETED	513	509
Overall Study NOT COMPLETED	16	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Tezepelumab 210mg Q4W Tezepelumab administered every 4 weeks subcutaneously	Placebo Placebo administered subcutaneously
Overall Study Withdrawal by Subject	8	15
Overall Study Death	0	2
Overall Study Lost to Follow-up	5	2
Overall Study Did not receive treatment / Non-compliance with protocol / did not complete safety follow-up visits	3	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously	Total n=1059 Participants Total of all reporting groups
Age, Categorical <=18 years	41 Participants n=5 Participants	41 Participants n=7 Participants	82 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	391 Participants n=5 Participants	416 Participants n=7 Participants	807 Participants n=5 Participants
Age, Categorical >=65 years	96 Participants n=5 Participants	74 Participants n=7 Participants	170 Participants n=5 Participants
Age, Continuous	49.9 Years STANDARD_DEVIATION 16.3 • n=5 Participants	49.0 Years STANDARD_DEVIATION 15.9 • n=7 Participants	49.5 Years STANDARD_DEVIATION 16.1 • n=5 Participants
Sex: Female, Male Female	335 Participants n=5 Participants	337 Participants n=7 Participants	672 Participants n=5 Participants
Sex: Female, Male Male	193 Participants n=5 Participants	194 Participants n=7 Participants	387 Participants n=5 Participants
Race/Ethnicity, Customized White	332 Participants n=5 Participants	327 Participants n=7 Participants	659 Participants n=5 Participants
Race/Ethnicity, Customized Black of African American	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Asian	146 Participants n=5 Participants	149 Participants n=7 Participants	295 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	19 Participants n=5 Participants	23 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	83 Participants n=5 Participants	81 Participants n=7 Participants	164 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	445 Participants n=5 Participants	450 Participants n=7 Participants	895 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomisation to Study Week 52.

The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set)

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma	0.93 events per year Interval 0.8 to 1.07	2.10 events per year Interval 1.84 to 2.39

PRIMARY outcome

Timeframe: From randomisation to Study Week 52.

The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils \< 300 cells/uL

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=309 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=309 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL	1.02 events per year Interval 0.84 to 1.23	1.73 events per year Interval 1.46 to 2.05

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Population: Number of participants analyzed is the number of subjects with an observation at Week 52. All subjects from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

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.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=471 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=453 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint)	0.23 Litre Standard Error 0.018	0.10 Litre Standard Error 0.018

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=480 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=467 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint)	1.48 Scale of score Standard Error 0.049	1.14 Scale of score Standard Error 0.049

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=485 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=472 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint)	-1.53 Scale of score Standard Error 0.045	-1.20 Scale of score Standard Error 0.046

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Population: Number of participants analyzed is the number of subjects with a weekly mean at Week 52. All subjects from the Full Analysis Set with at least one change from baseline weekly mean at any post-baseline week contributes to the analyses.

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.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=374 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=355 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint)	-0.70 Scale of score Standard Error 0.027	-0.59 Scale of score Standard Error 0.027

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Time to First Asthma Exacerbation	231 Participants	319 Participants

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=440 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=426 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb)	-17.29 ppb Standard Error 1.156	-3.46 ppb Standard Error 1.165

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x \[number of night nebulizer times\] + number of daytime inhaler puffs + 2 x \[number of day nebulizer times\]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=439 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=428 Participants Placebo administered subcutaneously
Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52	-2.53 weekly mean rescue medication use Standard Error 0.137	-2.36 weekly mean rescue medication use Standard Error 0.137

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Population: The work productivity loss is only applicable to subjects who were employed, which is a subset of the study population.

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.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=185 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=177 Participants Placebo administered subcutaneously
Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52	-20.16 Percentage of work productivity loss Standard Deviation 30.31	-16.58 Percentage of work productivity loss Standard Deviation 29.46

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Population: The class productivity loss is only applicable to subjects attending school, which is a subset of the study population.

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.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=15 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=19 Participants Placebo administered subcutaneously
Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52	-14.03 Percentage of class productivity loss Standard Deviation 33.00	-24.72 Percentage of class productivity loss Standard Deviation 26.48

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=401 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=393 Participants Placebo administered subcutaneously
Activity Impairment at Week 52	-20.0 Percentage of activity impairment Standard Deviation 28.6	-17.9 Percentage of activity impairment Standard Deviation 27.1

SECONDARY outcome

Timeframe: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64

Population: Number of subjects who received at least one dose of IP. Number analysed at each timepoint is a subset of this based on subjects who had sample results available at that timepoint. The placebo arm is not applicable since it is not the experimental product.

Mean serum trough PK concentrations taken pre-dose at each visit

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo Placebo administered subcutaneously
Pharmacokinetics of Tezepelumab Baseline	0 ug/mL Geometric Coefficient of Variation 0	—
Pharmacokinetics of Tezepelumab Week 4	10.1573 ug/mL Geometric Coefficient of Variation 74.51	—
Pharmacokinetics of Tezepelumab Week 12	18.7396 ug/mL Geometric Coefficient of Variation 48.53	—
Pharmacokinetics of Tezepelumab Week 24	20.1924 ug/mL Geometric Coefficient of Variation 51.77	—
Pharmacokinetics of Tezepelumab Week 36	19.5246 ug/mL Geometric Coefficient of Variation 55.58	—
Pharmacokinetics of Tezepelumab Week 52	19.8894 ug/mL Geometric Coefficient of Variation 70.04	—
Pharmacokinetics of Tezepelumab Week 64	1.7675 ug/mL Geometric Coefficient of Variation 171.86	—

SECONDARY outcome

Timeframe: At Study Week 52

Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=448 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=435 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in EQ-5D-5L VAS	14.64 scale of score Standard Error 0.708	11.86 scale of score Standard Error 0.712

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse)

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=483 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=477 Participants Placebo administered subcutaneously
Clinicians Global Impression of Change at Week 52 Very much improved	96 Participants	60 Participants
Clinicians Global Impression of Change at Week 52 Much improved	199 Participants	132 Participants
Clinicians Global Impression of Change at Week 52 Minimally improved	98 Participants	131 Participants
Clinicians Global Impression of Change at Week 52 No change	77 Participants	130 Participants
Clinicians Global Impression of Change at Week 52 Minimally worse	11 Participants	19 Participants
Clinicians Global Impression of Change at Week 52 Much worse	2 Participants	4 Participants
Clinicians Global Impression of Change at Week 52 Very much worse	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=479 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=466 Participants Placebo administered subcutaneously
Patients Global Impression of Change at Week 52 Very much improved	255 Participants	182 Participants
Patients Global Impression of Change at Week 52 Much Improved	103 Participants	94 Participants
Patients Global Impression of Change at Week 52 Minimally improved	71 Participants	76 Participants
Patients Global Impression of Change at Week 52 No change	39 Participants	99 Participants
Patients Global Impression of Change at Week 52 Minimally worse	6 Participants	8 Participants
Patients Global Impression of Change at Week 52 Much worse	4 Participants	6 Participants
Patients Global Impression of Change at Week 52 Very much worse	1 Participants	1 Participants

SECONDARY outcome

Timeframe: At Study Week 52

PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=479 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=466 Participants Placebo administered subcutaneously
Patients Global Impression of Severity at Week 52 No symptoms	118 Participants	78 Participants
Patients Global Impression of Severity at Week 52 Very mild symptoms	138 Participants	128 Participants
Patients Global Impression of Severity at Week 52 Mild symptoms	110 Participants	128 Participants
Patients Global Impression of Severity at Week 52 Moderate symptoms	99 Participants	111 Participants
Patients Global Impression of Severity at Week 52 Severe symptoms	14 Participants	19 Participants
Patients Global Impression of Severity at Week 52 Very severe symptoms	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=458 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=451 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL)	-170.02 cells/uL Standard Error 9.222	-40.15 cells/uL Standard Error 9.254

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=482 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=471 Participants Placebo administered subcutaneously
Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL)	-164.38 IU/mL Standard Error 34.414	43.61 IU/mL Standard Error 34.542

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Hospitalisation	17 Participants	37 Participants
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Emergency Room visit	23 Participants	50 Participants
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Unscheduled visit to specialist	187 Participants	231 Participants
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Home visit	9 Participants	10 Participants
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Telephone call	101 Participants	133 Participants
Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks Ambulance transport	4 Participants	12 Participants

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=414 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=391 Participants Placebo administered subcutaneously
Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)	34.57 L/min Standard Error 3.051	18.01 L/min Standard Error 3.074

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=405 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=390 Participants Placebo administered subcutaneously
Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)	23.87 L/min Standard Error 3.075	9.01 L/min Standard Error 3.094

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=418 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=395 Participants Placebo administered subcutaneously
Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52	-33.51 percentage of nights with awakenings Standard Error 1.381	-30.22 percentage of nights with awakenings Standard Error 1.387

SECONDARY outcome

Timeframe: Baseline, and from time of first dose at Week 0 to end of study at Week 64.

Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post baseline assessments (with \>=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=527 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=530 Participants Placebo administered subcutaneously
Immunogenecity of Tezepelumab Treatment boosted ADA positive	1 Participants	2 Participants
Immunogenecity of Tezepelumab Treatment emergent ADA positive	10 Participants	20 Participants
Immunogenecity of Tezepelumab ADA persistently positive	4 Participants	18 Participants
Immunogenecity of Tezepelumab ADA transiently positive	8 Participants	18 Participants
Immunogenecity of Tezepelumab ADA positive at baseline and/or post-baseline	26 Participants	44 Participants
Immunogenecity of Tezepelumab Any baseline ADA positive	17 Participants	25 Participants
Immunogenecity of Tezepelumab Only baseline ADA positive	14 Participants	8 Participants
Immunogenecity of Tezepelumab Any post-baseline ADA positive	12 Participants	36 Participants
Immunogenecity of Tezepelumab Both baseline and >= 1 post-baseline ADA positive	3 Participants	17 Participants
Immunogenecity of Tezepelumab Treatment induced ADA positive	9 Participants	18 Participants

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Proportion of Subjects Who Had no Asthma Exacerbations	54.2 Percentage	38.6 Percentage

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF)

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation	0.06 events per year Interval 0.04 to 0.09	0.28 events per year Interval 0.2 to 0.39

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation	4.7 Percentage	12.2 Percentage

SECONDARY outcome

Timeframe: From randomisation to Study Week 52

The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation	92.4 Percentage	85.1 Percentage

OTHER_PRE_SPECIFIED outcome

Timeframe: From randomisation to Study Week 52

The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate Associated With Hospitalisations	0.03 events per year Interval 0.01 to 0.06	0.19 events per year Interval 0.12 to 0.3

OTHER_PRE_SPECIFIED outcome

Timeframe: From randomisation to Study Week 52

The annualized exacerbation rate is based on exacerbations as defined for the primary endpoint, but any hospitalisation and ER visits which are adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate Using Adjudicated Data	0.94 events per year Interval 0.81 to 1.09	2.14 events per year Interval 1.88 to 2.44

OTHER_PRE_SPECIFIED outcome

Timeframe: From randomisation to Study Week 52

The annualized exacerbation rate is based on exacerbations associated with hospitalisations or ER visits, where hospitalisation and ER visits adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.

Outcome measures

Outcome measures
Measure	Tezepelumab 210mg Q4W n=528 Participants Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 Participants Placebo administered subcutaneously
Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data	0.08 events per year Interval 0.05 to 0.12	0.31 events per year Interval 0.22 to 0.42

Adverse Events

Tezepelumab 210mg Q4W

Serious events: 52 serious events

Other events: 306 other events

Deaths: 0 deaths

Placebo

Serious events: 73 serious events

Other events: 331 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Head

AstraZeneca

Phone: +1 302 885 1180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tezepelumab 210mg Q4W n=528 participants at risk Tezepelumab administered every 4 weeks subcutaneously	Placebo n=531 participants at risk Placebo administered subcutaneously
Infections and infestations Bronchitis bacterial	4.5% 24/528 • Number of events 26 • From first dose of study drug until end of study at Week 64.	3.2% 17/531 • Number of events 20 • From first dose of study drug until end of study at Week 64.
Infections and infestations Urinary tract infection	4.2% 22/528 • Number of events 33 • From first dose of study drug until end of study at Week 64.	4.1% 22/531 • Number of events 24 • From first dose of study drug until end of study at Week 64.
Infections and infestations Viral upper respiratory tract infection	3.2% 17/528 • Number of events 21 • From first dose of study drug until end of study at Week 64.	2.4% 13/531 • Number of events 18 • From first dose of study drug until end of study at Week 64.
General disorders Influenza like illness	3.6% 19/528 • Number of events 21 • From first dose of study drug until end of study at Week 64.	4.1% 22/531 • Number of events 26 • From first dose of study drug until end of study at Week 64.
Infections and infestations Bronchitis	4.7% 25/528 • Number of events 39 • From first dose of study drug until end of study at Week 64.	6.2% 33/531 • Number of events 36 • From first dose of study drug until end of study at Week 64.
Infections and infestations Gastroenteritis	3.2% 17/528 • Number of events 18 • From first dose of study drug until end of study at Week 64.	2.6% 14/531 • Number of events 15 • From first dose of study drug until end of study at Week 64.
Infections and infestations Nasopharyngitis	21.4% 113/528 • Number of events 172 • From first dose of study drug until end of study at Week 64.	21.5% 114/531 • Number of events 188 • From first dose of study drug until end of study at Week 64.
Infections and infestations Pharyngitis	3.2% 17/528 • Number of events 18 • From first dose of study drug until end of study at Week 64.	2.8% 15/531 • Number of events 17 • From first dose of study drug until end of study at Week 64.
Infections and infestations Rhinitis	2.7% 14/528 • Number of events 18 • From first dose of study drug until end of study at Week 64.	3.2% 17/531 • Number of events 37 • From first dose of study drug until end of study at Week 64.
Infections and infestations Sinusitis	3.6% 19/528 • Number of events 22 • From first dose of study drug until end of study at Week 64.	7.5% 40/531 • Number of events 56 • From first dose of study drug until end of study at Week 64.
Infections and infestations Upper respiratory tract infection	11.0% 58/528 • Number of events 94 • From first dose of study drug until end of study at Week 64.	16.6% 88/531 • Number of events 129 • From first dose of study drug until end of study at Week 64.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 20/528 • Number of events 25 • From first dose of study drug until end of study at Week 64.	2.4% 13/531 • Number of events 14 • From first dose of study drug until end of study at Week 64.
Musculoskeletal and connective tissue disorders Back pain	4.0% 21/528 • Number of events 26 • From first dose of study drug until end of study at Week 64.	2.8% 15/531 • Number of events 16 • From first dose of study drug until end of study at Week 64.
Nervous system disorders Headache	8.1% 43/528 • Number of events 96 • From first dose of study drug until end of study at Week 64.	8.5% 45/531 • Number of events 68 • From first dose of study drug until end of study at Week 64.
Respiratory, thoracic and mediastinal disorders Asthma	2.7% 14/528 • Number of events 17 • From first dose of study drug until end of study at Week 64.	4.3% 23/531 • Number of events 25 • From first dose of study drug until end of study at Week 64.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	3.0% 16/528 • Number of events 19 • From first dose of study drug until end of study at Week 64.	3.2% 17/531 • Number of events 25 • From first dose of study drug until end of study at Week 64.
Vascular disorders Hypertension	4.4% 23/528 • Number of events 27 • From first dose of study drug until end of study at Week 64.	4.1% 22/531 • Number of events 29 • From first dose of study drug until end of study at Week 64.