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

Asthma Clinical Trial

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Official title:

A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03347279
• Other study ID #: D5180C00007
• Status: Completed
• Phase: Phase 3
• Start date: November 23, 2017
• Est. completion date: November 12, 2020

Study information

• Verified date: October 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma

Description:

This is a multicentre, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 1060 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1061
• Est. completion date: November 12, 2020
• Est. primary completion date: September 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age. 12-80
• Documented physician-diagnosed asthma for at least 12 months
• Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months.
• Documented treatment with a total daily dose of either medium or high dose ICS (= 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months.
• At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
• Morning pre-BD FEV1 <80% predicted normal (<90% for subjects 12-17 yrs)
• Evidence of asthma as documented by either: Documented historical reversibility of FEV1 =12% and =200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 =12% and =200 mL during screening.
• Documented history of at least 2 asthma exacerbation events within 12 months.
• ACQ-6 score =1.5 at screening and on day of randomization

Exclusion Criteria:

• Pulmonary disease other than asthma.
• History of cancer.
• History of a clinically significant infection.
• Current smokers or subjects with smoking history =10 pack-years and subjects using vaping products, including electronic cigarettes.
• History of chronic alcohol or drug abuse within 12 months.
• Hepatitis B, C or HIV.
• Pregnant or breastfeeding.
• History of anaphylaxis following any biologic therapy.
• Subject randomized in the current study or previous tezepelumab studies.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Experimental: Tezepelumab
Tezepelumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Mendoza
Argentina	Research Site	Nueve de julio
Argentina	Research Site	Quilmes
Australia	Research Site	Campbelltown
Australia	Research Site	Kent Town
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	New Lambton
Australia	Research Site	Spearwood
Australia	Research Site	Westmead
Australia	Research Site	Woolloongabba
Austria	Research Site	Klagenfurt
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Austria	Research Site	Wien
Brazil	Research Site	Blumenau
Brazil	Research Site	Botucatu
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Salvador
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sorocaba
Brazil	Research Site	Vitória
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Windsor	Ontario
France	Research Site	Brest Cedex
France	Research Site	GRENOBLE Cedex 9
France	Research Site	Le Kremlin Bicêtre
France	Research Site	Lille Cedex
France	Research Site	Lyon Cedex 04
France	Research Site	MARSEILLE Cedex 20
France	Research Site	Montpellier Cedex 5
France	Research Site	Nantes Cedex 1
France	Research Site	Paris
France	Research Site	PARIS Cedex 12
France	Research Site	Paris Cedex 18
France	Research Site	Pessac
France	Research Site	Strasbourg Cedex
France	Research Site	Toulouse CEDEX 09
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Landsberg
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Mainz
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Rehovot
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Edogawa-ku
Japan	Research Site	Fujieda-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Habikino-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Higashiibaraki-gun
Japan	Research Site	Himeji-shi
Japan	Research Site	Hitachi-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kasuga-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kitakyusyu
Japan	Research Site	Koga-shi
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Meguro-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Mizunami-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Ogaki-shi
Japan	Research Site	Ohota-ku
Japan	Research Site	Omuta-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Setagaya-ku
Japan	Research Site	Shibuya-ku
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sumida-ku
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Ube
Japan	Research Site	Yokkaichi-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yoshida-gun
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Jeju-si
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	St-Petersburg
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
South Africa	Research Site	Bellville
South Africa	Research Site	Boksburg North
South Africa	Research Site	Cape Town
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Lenasia Ext8
South Africa	Research Site	Middelburg
South Africa	Research Site	Mowbray
South Africa	Research Site	Parow
South Africa	Research Site	Pretoria
South Africa	Research Site	Umkomaas
South Africa	Research Site	Witbank
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Kaohsiung Hsien
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Yilan
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv Region
United Kingdom	Research Site	London
United States	Research Site	Allen	Texas
United States	Research Site	Amarillo	Texas
United States	Research Site	Anderson	South Carolina
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Bakersfield	California
United States	Research Site	Boerne	Texas
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Celebration	Florida
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	South Carolina
United States	Research Site	Cudahy	Wisconsin
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Dothan	Alabama
United States	Research Site	Edmond	Oklahoma
United States	Research Site	Encinitas	California
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Fayetteville	Georgia
United States	Research Site	Flint	Michigan
United States	Research Site	Foley	Alabama
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Gainesville	Georgia
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Gilbert	Arizona
United States	Research Site	Greenville	South Carolina
United States	Research Site	Huntington Beach	California
United States	Research Site	Kissimmee	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lake Charles	Louisiana
United States	Research Site	Lampasas	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Manassas	Virginia
United States	Research Site	Mayfield Heights	Ohio
United States	Research Site	McAllen	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Michigan City	Indiana
United States	Research Site	Mission Viejo	California
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newport Beach	California
United States	Research Site	Northfield	New Jersey
United States	Research Site	Northridge	California
United States	Research Site	Novi	Michigan
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Palm Desert	California
United States	Research Site	Panama City	Florida
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Plano	Texas
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Port Huron	Michigan
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Rolling Hills Estates	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Sarasota	Florida
United States	Research Site	Savannah	Georgia
United States	Research Site	Sebring	Florida
United States	Research Site	Stockbridge	Georgia
United States	Research Site	Tampa	Florida
United States	Research Site	Toledo	Ohio
United States	Research Site	Toms River	New Jersey
United States	Research Site	Troy	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Valhalla	New York
United States	Research Site	Walnut Creek	California
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Westminster	California
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Zachary	Louisiana
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Brazil,  Canada,  France,  Germany,  Israel,  Japan,  Korea, Republic of,  Russian Federation,  Saudi Arabia,  South Africa,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Annual Asthma Exacerbation Rate Associated With Hospitalisations	The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization	From randomisation to Study Week 52
Other	Annual Asthma Exacerbation Rate Using Adjudicated Data	The annualized exacerbation rate is based on exacerbations as defined for the primary endpoint, but any hospitalisation and ER visits which are adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.	From randomisation to Study Week 52
Other	Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data	The annualized exacerbation rate is based on exacerbations associated with hospitalisations or ER visits, where hospitalisation and ER visits adjudicated to be asthma related are added, and those adjudicated to not be asthma related are removed from analyses.	From randomisation to Study Week 52
Primary	Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma	The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set)	From randomisation to Study Week 52.
Primary	Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL	The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils < 300 cells/uL	From randomisation to Study Week 52.
Secondary	Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint)	Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint)	Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).	From randomisation to Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint)	Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting ß2-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.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint)	Mean change from baseline at Week 52 in Asthma Symptom Diary. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4, where 0 indicates no asthma symptoms.	From randomisation to Study Week 52
Secondary	Time to First Asthma Exacerbation	Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb)	Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52	Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of daytime inhaler puffs + 2 x [number of day nebulizer times]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52	WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52	WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Class productivity loss is derived by sum of percentage of missed class hours due to asthma and product of percentage of actual hours in class times degree of asthma affecting productivity while in class. Percentage of missed hours in class due to asthma is calculated by number of hours in class missed due to asthma divided by total number of hours in class missed plus number of hours actually in class.	From randomisation to Study Week 52
Secondary	Activity Impairment at Week 52	WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.	From randomisation to Study Week 52
Secondary	Pharmacokinetics of Tezepelumab	Mean serum trough PK concentrations taken pre-dose at each visit	Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64
Secondary	Mean Change From Baseline at Week 52 in EQ-5D-5L VAS	Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.	At Study Week 52
Secondary	Clinicians Global Impression of Change at Week 52	CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse)	From randomisation to Study Week 52
Secondary	Patients Global Impression of Change at Week 52	PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse).	From randomisation to Study Week 52
Secondary	Patients Global Impression of Severity at Week 52	PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms	At Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL)	Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)	From randomisation to Study Week 52
Secondary	Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL)	Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)	From randomisation to Study Week 52
Secondary	Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks	Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)	Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)	Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.	From randomisation to Study Week 52
Secondary	Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52	Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.	From randomisation to Study Week 52
Secondary	Immunogenecity of Tezepelumab	Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.	Baseline, and from time of first dose at Week 0 to end of study at Week 64.
Secondary	Proportion of Subjects Who Had no Asthma Exacerbations	The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.	From randomisation to Study Week 52
Secondary	Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation	The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF)	From randomisation to Study Week 52
Secondary	Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation	Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation.	From randomisation to Study Week 52
Secondary	Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation	The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period.	From randomisation to Study Week 52

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