NAVIGATOR: Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT03347279
Collaborator
Amgen (Industry)
1,061
289
2
35.6
3.7
0.1
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1061 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-Blind
Primary Purpose:
Treatment
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)
Actual Study Start Date
:
Nov 23, 2017
Actual Primary Completion Date
:
Sep 8, 2020
Actual Study Completion Date
:
Nov 12, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tezepelumab Tezepelumab: Tezepelumab subcutaneous injection |
Biological: Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Other Names:
|
| Placebo Comparator: Placebo Placebo: Placebo subcutaneous injection |
Other: Placebo
Placebo subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma [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)
- Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL [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
Secondary Outcome Measures
- 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) [From randomisation to Study Week 52]
Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
- Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint) [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).
- Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) [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.
- Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) [From randomisation to Study Week 52]
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 to First Asthma Exacerbation [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.
- Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) [From randomisation to Study Week 52]
Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site
- Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 [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.
- Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 [From randomisation to Study 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.
- Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 [From randomisation to Study 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.
- Activity Impairment at Week 52 [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.
- Pharmacokinetics of Tezepelumab [Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64]
Mean serum trough PK concentrations taken pre-dose at each visit
- Mean Change From Baseline at Week 52 in EQ-5D-5L VAS [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.
- Clinicians Global Impression of Change at Week 52 [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)
- Patients Global Impression of Change at Week 52 [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).
- Patients Global Impression of Severity at Week 52 [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
- Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) [From randomisation to Study Week 52]
Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)
- Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) [From randomisation to Study Week 52]
Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)
- Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks [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
- Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) [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.
- Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) [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.
- Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 [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.
- Immunogenecity of Tezepelumab [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.
- Proportion of Subjects Who Had no Asthma Exacerbations [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.
- Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation [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)
- Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation [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.
- Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation [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.
Other Outcome Measures
- Annual Asthma Exacerbation Rate Associated With Hospitalisations [From randomisation to Study Week 52]
The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with hospitalization
- Annual Asthma Exacerbation Rate Using Adjudicated Data [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.
- Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Dothan | Alabama | United States | 36303 |
| 2 | Research Site | Foley | Alabama | United States | 36535 |
| 3 | Research Site | Gilbert | Arizona | United States | 85234 |
| 4 | Research Site | Tucson | Arizona | United States | 85724 |
| 5 | Research Site | Bakersfield | California | United States | 93301 |
| 6 | Research Site | Encinitas | California | United States | 92024 |
| 7 | Research Site | Huntington Beach | California | United States | 92647 |
| 8 | Research Site | Long Beach | California | United States | 90808 |
| 9 | Research Site | Los Angeles | California | United States | 90025 |
| 10 | Research Site | Mission Viejo | California | United States | 92691 |
| 11 | Research Site | Newport Beach | California | United States | 92663 |
| 12 | Research Site | Northridge | California | United States | 91324 |
| 13 | Research Site | Palm Desert | California | United States | 92260 |
| 14 | Research Site | Rolling Hills Estates | California | United States | 90274 |
| 15 | Research Site | Walnut Creek | California | United States | 94598 |
| 16 | Research Site | Westminster | California | United States | 92683 |
| 17 | Research Site | Denver | Colorado | United States | 80206 |
| 18 | Research Site | New Haven | Connecticut | United States | 06520 |
| 19 | Research Site | Celebration | Florida | United States | 34747 |
| 20 | Research Site | Kissimmee | Florida | United States | 34741 |
| 21 | Research Site | Kissimmee | Florida | United States | 34744 |
| 22 | Research Site | Orlando | Florida | United States | 32803 |
| 23 | Research Site | Orlando | Florida | United States | 32825 |
| 24 | Research Site | Panama City | Florida | United States | 32405 |
| 25 | Research Site | Port Charlotte | Florida | United States | 33952 |
| 26 | Research Site | Saint Petersburg | Florida | United States | 33704 |
| 27 | Research Site | Saint Petersburg | Florida | United States | 33710 |
| 28 | Research Site | Saint Petersburg | Florida | United States | 33713 |
| 29 | Research Site | Sarasota | Florida | United States | 34239 |
| 30 | Research Site | Sebring | Florida | United States | 33870 |
| 31 | Research Site | Tampa | Florida | United States | 33607 |
| 32 | Research Site | Winter Park | Florida | United States | 32789 |
| 33 | Research Site | Fayetteville | Georgia | United States | 30214 |
| 34 | Research Site | Gainesville | Georgia | United States | 30501 |
| 35 | Research Site | Savannah | Georgia | United States | 31406 |
| 36 | Research Site | Stockbridge | Georgia | United States | 30281 |
| 37 | Research Site | Boise | Idaho | United States | 83706 |
| 38 | Research Site | Michigan City | Indiana | United States | 46360 |
| 39 | Research Site | Fort Mitchell | Kentucky | United States | 41017 |
| 40 | Research Site | Louisville | Kentucky | United States | 40215 |
| 41 | Research Site | Lake Charles | Louisiana | United States | 70601 |
| 42 | Research Site | Zachary | Louisiana | United States | 70791 |
| 43 | Research Site | White Marsh | Maryland | United States | 21162 |
| 44 | Research Site | Boston | Massachusetts | United States | 02115 |
| 45 | Research Site | Fall River | Massachusetts | United States | 02721 |
| 46 | Research Site | Ann Arbor | Michigan | United States | 48109 |
| 47 | Research Site | Flint | Michigan | United States | 48504 |
| 48 | Research Site | Novi | Michigan | United States | 48375 |
| 49 | Research Site | Port Huron | Michigan | United States | 48060 |
| 50 | Research Site | Troy | Michigan | United States | 48085 |
| 51 | Research Site | Saint Louis | Missouri | United States | 63108 |
| 52 | Research Site | Saint Louis | Missouri | United States | 63141 |
| 53 | Research Site | Lincoln | Nebraska | United States | 68505 |
| 54 | Research Site | Las Vegas | Nevada | United States | 89106 |
| 55 | Research Site | Las Vegas | Nevada | United States | 89119 |
| 56 | Research Site | Northfield | New Jersey | United States | 08225 |
| 57 | Research Site | Toms River | New Jersey | United States | 08755 |
| 58 | Research Site | Bronx | New York | United States | 10459 |
| 59 | Research Site | Bronx | New York | United States | 10465 |
| 60 | Research Site | Brooklyn | New York | United States | 11235 |
| 61 | Research Site | New York | New York | United States | 10016 |
| 62 | Research Site | New York | New York | United States | 10022 |
| 63 | Research Site | New York | New York | United States | 10029 |
| 64 | Research Site | New York | New York | United States | 10032 |
| 65 | Research Site | Valhalla | New York | United States | 10595 |
| 66 | Research Site | Charlotte | North Carolina | United States | 28277 |
| 67 | Research Site | Gastonia | North Carolina | United States | 28054 |
| 68 | Research Site | Winston-Salem | North Carolina | United States | 27104 |
| 69 | Research Site | Cincinnati | Ohio | United States | 45229 |
| 70 | Research Site | Cincinnati | Ohio | United States | 45231 |
| 71 | Research Site | Mayfield Heights | Ohio | United States | 44124 |
| 72 | Research Site | Toledo | Ohio | United States | 43608 |
| 73 | Research Site | Edmond | Oklahoma | United States | 73034 |
| 74 | Research Site | Oklahoma City | Oklahoma | United States | 73120 |
| 75 | Research Site | Tulsa | Oklahoma | United States | 74136 |
| 76 | Research Site | Medford | Oregon | United States | 97504 |
| 77 | Research Site | Pittsburgh | Pennsylvania | United States | 15243 |
| 78 | Research Site | Warwick | Rhode Island | United States | 02886 |
| 79 | Research Site | Anderson | South Carolina | United States | 29621 |
| 80 | Research Site | Columbia | South Carolina | United States | 29204 |
| 81 | Research Site | Greenville | South Carolina | United States | 29607 |
| 82 | Research Site | Allen | Texas | United States | 75013 |
| 83 | Research Site | Amarillo | Texas | United States | 79106 |
| 84 | Research Site | Boerne | Texas | United States | 78006 |
| 85 | Research Site | Dallas | Texas | United States | 75225 |
| 86 | Research Site | Dallas | Texas | United States | 75230 |
| 87 | Research Site | Lampasas | Texas | United States | 76550 |
| 88 | Research Site | McAllen | Texas | United States | 78504 |
| 89 | Research Site | Plano | Texas | United States | 75093 |
| 90 | Research Site | San Antonio | Texas | United States | 78251 |
| 91 | Research Site | Manassas | Virginia | United States | 20110 |
| 92 | Research Site | Richmond | Virginia | United States | 23220 |
| 93 | Research Site | Richmond | Virginia | United States | 23235 |
| 94 | Research Site | Cudahy | Wisconsin | United States | 53110 |
| 95 | Research Site | Madison | Wisconsin | United States | 53792 |
| 96 | Research Site | Buenos Aires | Argentina | C1414AIF | |
| 97 | Research Site | Caba | Argentina | C1056ABJ | |
| 98 | Research Site | Caba | Argentina | C1425BEN | |
| 99 | Research Site | Ciudad de Buenos Aires | Argentina | 1425 | |
| 100 | Research Site | Córdoba | Argentina | X5003DCE | |
| 101 | Research Site | Mendoza | Argentina | 5500 | |
| 102 | Research Site | Nueve de julio | Argentina | B6500EZL | |
| 103 | Research Site | Quilmes | Argentina | B1878FNR | |
| 104 | Research Site | Campbelltown | Australia | 2560 | |
| 105 | Research Site | Kent Town | Australia | 5067 | |
| 106 | Research Site | Melbourne | Australia | 3004 | |
| 107 | Research Site | Nedlands | Australia | 6009 | |
| 108 | Research Site | New Lambton | Australia | 2310 | |
| 109 | Research Site | Spearwood | Australia | 6163 | |
| 110 | Research Site | Westmead | Australia | 2145 | |
| 111 | Research Site | Woolloongabba | Australia | 4102 | |
| 112 | Research Site | Klagenfurt | Austria | 9020 | |
| 113 | Research Site | Linz | Austria | 4020 | |
| 114 | Research Site | Salzburg | Austria | 5020 | |
| 115 | Research Site | Wien | Austria | 1090 | |
| 116 | Research Site | Wien | Austria | 1130 | |
| 117 | Research Site | Blumenau | Brazil | 89030-101 | |
| 118 | Research Site | Botucatu | Brazil | 18618-970 | |
| 119 | Research Site | Curitiba | Brazil | 80060-900 | |
| 120 | Research Site | Porto Alegre | Brazil | 9002-060 | |
| 121 | Research Site | Porto Alegre | Brazil | 90035-074 | |
| 122 | Research Site | Porto Alegre | Brazil | 90610-000 | |
| 123 | Research Site | Porto Alegre | Brazil | 90619-900 | |
| 124 | Research Site | Porto Alegre | Brazil | 91350-200 | |
| 125 | Research Site | Recife | Brazil | 50070-550 | |
| 126 | Research Site | Salvador | Brazil | 41940-455 | |
| 127 | Research Site | Santo Andre | Brazil | 09080-110 | |
| 128 | Research Site | Sao Bernardo do Campo | Brazil | 09750-420 | |
| 129 | Research Site | Sorocaba | Brazil | 18040-425 | |
| 130 | Research Site | Vitória | Brazil | 29055-450 | |
| 131 | Research Site | Calgary | Alberta | Canada | T2N 4Z6 |
| 132 | Research Site | Sherwood Park | Alberta | Canada | T8L 0N2 |
| 133 | Research Site | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 134 | Research Site | Ajax | Ontario | Canada | L1S 2J5 |
| 135 | Research Site | Burlington | Ontario | Canada | L7N 3V2 |
| 136 | Research Site | Mississauga | Ontario | Canada | L5A 3V4 |
| 137 | Research Site | Ottawa | Ontario | Canada | K1G 6C6 |
| 138 | Research Site | Windsor | Ontario | Canada | N8X 1T3 |
| 139 | Research Site | Montreal | Quebec | Canada | H4J 1C5 |
| 140 | Research Site | St Charles Borromee | Quebec | Canada | J6E 2B4 |
| 141 | Research Site | Trois-Rivières | Quebec | Canada | G8T 7A1 |
| 142 | Research Site | Quebec | Canada | G1G 3Y8 | |
| 143 | Research Site | Brest Cedex | France | 29609 | |
| 144 | Research Site | GRENOBLE Cedex 9 | France | 38043 | |
| 145 | Research Site | Le Kremlin Bicêtre | France | 94275 | |
| 146 | Research Site | Lille Cedex | France | 59037 | |
| 147 | Research Site | Lyon Cedex 04 | France | 69317 | |
| 148 | Research Site | MARSEILLE Cedex 20 | France | 13015 | |
| 149 | Research Site | Montpellier Cedex 5 | France | 34295 | |
| 150 | Research Site | Nantes Cedex 1 | France | 44093 | |
| 151 | Research Site | PARIS Cedex 12 | France | 75571 | |
| 152 | Research Site | Paris Cedex 18 | France | 75877 | |
| 153 | Research Site | Paris | France | 75015 | |
| 154 | Research Site | Pessac | France | 33604 | |
| 155 | Research Site | Strasbourg Cedex | France | 67091 | |
| 156 | Research Site | Toulouse CEDEX 09 | France | 31059 | |
| 157 | Research Site | Bamberg | Germany | 96049 | |
| 158 | Research Site | Berlin | Germany | 10367 | |
| 159 | Research Site | Berlin | Germany | 10717 | |
| 160 | Research Site | Frankfurt am Main | Germany | 60596 | |
| 161 | Research Site | Frankfurt | Germany | 60596 | |
| 162 | Research Site | Hamburg | Germany | 20354 | |
| 163 | Research Site | Hamburg | Germany | 22299 | |
| 164 | Research Site | Hannover | Germany | 30625 | |
| 165 | Research Site | Hannover | Germany | D-30173 | |
| 166 | Research Site | Landsberg | Germany | 86899 | |
| 167 | Research Site | Leipzig | Germany | 04103 | |
| 168 | Research Site | Leipzig | Germany | 04357 | |
| 169 | Research Site | Lübeck | Germany | 23552 | |
| 170 | Research Site | Mainz | Germany | 55131 | |
| 171 | Research Site | Ashkelon | Israel | 7830604 | |
| 172 | Research Site | Haifa | Israel | 34362 | |
| 173 | Research Site | Jerusalem | Israel | 91031 | |
| 174 | Research Site | Jerusalem | Israel | 91120 | |
| 175 | Research Site | Kfar Saba | Israel | 49281 | |
| 176 | Research Site | Rehovot | Israel | 7661041 | |
| 177 | Research Site | Bunkyo-ku | Japan | 113-8431 | |
| 178 | Research Site | Chuo-ku | Japan | 103-0022 | |
| 179 | Research Site | Chuo-ku | Japan | 103-0028 | |
| 180 | Research Site | Chuo-ku | Japan | 104-0031 | |
| 181 | Research Site | Edogawa-ku | Japan | 134-0083 | |
| 182 | Research Site | Fujieda-shi | Japan | 426-8677 | |
| 183 | Research Site | Fukuoka-shi | Japan | 810-0001 | |
| 184 | Research Site | Fukuoka-shi | Japan | 811-1394 | |
| 185 | Research Site | Fukuoka-shi | Japan | 815-8588 | |
| 186 | Research Site | Habikino-shi | Japan | 583-8588 | |
| 187 | Research Site | Hamamatsu-shi | Japan | 431-3192 | |
| 188 | Research Site | Higashiibaraki-gun | Japan | 311-3193 | |
| 189 | Research Site | Himeji-shi | Japan | 672-8064 | |
| 190 | Research Site | Hitachi-shi | Japan | 317-0077 | |
| 191 | Research Site | Itabashi-ku | Japan | 173-0003 | |
| 192 | Research Site | Itabashi-ku | Japan | 173-8610 | |
| 193 | Research Site | Kagoshima-shi | Japan | 890-0073 | |
| 194 | Research Site | Kagoshima-shi | Japan | 890-8520 | |
| 195 | Research Site | Kanazawa-shi | Japan | 920-8530 | |
| 196 | Research Site | Kanazawa-shi | Japan | 920-8641 | |
| 197 | Research Site | Kasuga-shi | Japan | 816-0813 | |
| 198 | Research Site | Kishiwada-shi | Japan | 596-8501 | |
| 199 | Research Site | Kitakyusyu | Japan | 802-0052 | |
| 200 | Research Site | Koga-shi | Japan | 811-3195 | |
| 201 | Research Site | Matsusaka-shi | Japan | 515-8544 | |
| 202 | Research Site | Meguro-ku | Japan | 152-0021 | |
| 203 | Research Site | Meguro-ku | Japan | 152-8621 | |
| 204 | Research Site | Minato-ku | Japan | 105-0003 | |
| 205 | Research Site | Minato-ku | Japan | 105-0004 | |
| 206 | Research Site | Minato-ku | Japan | 108-0014 | |
| 207 | Research Site | Mizunami-shi | Japan | 509-6134 | |
| 208 | Research Site | Nagaoka-shi | Japan | 940-2085 | |
| 209 | Research Site | Niigata-shi | Japan | 951-8520 | |
| 210 | Research Site | Ogaki-shi | Japan | 503-8502 | |
| 211 | Research Site | Ohota-ku | Japan | 145-0063 | |
| 212 | Research Site | Omuta-shi | Japan | 837-0911 | |
| 213 | Research Site | Sagamihara-shi | Japan | 228-0815 | |
| 214 | Research Site | Sapporo-shi | Japan | 001-0901 | |
| 215 | Research Site | Sapporo-shi | Japan | 064-0804 | |
| 216 | Research Site | Setagaya-ku | Japan | 157-0072 | |
| 217 | Research Site | Shibuya-ku | Japan | 150-0013 | |
| 218 | Research Site | Shinagawa-ku | Japan | 140-8522 | |
| 219 | Research Site | Shinagawa-ku | Japan | 142-8666 | |
| 220 | Research Site | Shinjuku-ku | Japan | 162-8655 | |
| 221 | Research Site | Shinjuku-ku | Japan | 162-8666 | |
| 222 | Research Site | Sumida-ku | Japan | 130-0015 | |
| 223 | Research Site | Takamatsu-shi | Japan | 761-8073 | |
| 224 | Research Site | Toshima-ku | Japan | 170-0003 | |
| 225 | Research Site | Toshima-ku | Japan | 171-0014 | |
| 226 | Research Site | Ube | Japan | 755-8505 | |
| 227 | Research Site | Yokkaichi-shi | Japan | 510-8567 | |
| 228 | Research Site | Yokohama-shi | Japan | 223-0059 | |
| 229 | Research Site | Yokohama-shi | Japan | 236-0004 | |
| 230 | Research Site | Yokohama-shi | Japan | 236-0024 | |
| 231 | Research Site | Yoshida-gun | Japan | 910-1193 | |
| 232 | Research Site | Bucheon-si | Korea, Republic of | 14584 | |
| 233 | Research Site | Cheongju-si | Korea, Republic of | 28644 | |
| 234 | Research Site | Daegu | Korea, Republic of | 41404 | |
| 235 | Research Site | Daegu | Korea, Republic of | 42415 | |
| 236 | Research Site | Jeju-si | Korea, Republic of | 690-767 | |
| 237 | Research Site | Jeonju-si | Korea, Republic of | 54907 | |
| 238 | Research Site | Seongnam-si | Korea, Republic of | 13620 | |
| 239 | Research Site | Seoul | Korea, Republic of | 02447 | |
| 240 | Research Site | Seoul | Korea, Republic of | 03080 | |
| 241 | Research Site | Seoul | Korea, Republic of | 03312 | |
| 242 | Research Site | Seoul | Korea, Republic of | 03722 | |
| 243 | Research Site | Seoul | Korea, Republic of | 05505 | |
| 244 | Research Site | Seoul | Korea, Republic of | 06351 | |
| 245 | Research Site | Seoul | Korea, Republic of | 06591 | |
| 246 | Research Site | Seoul | Korea, Republic of | 07985 | |
| 247 | Research Site | Seoul | Korea, Republic of | 08308 | |
| 248 | Research Site | Seoul | Korea, Republic of | 150-713 | |
| 249 | Research Site | Suwon-si | Korea, Republic of | 16499 | |
| 250 | Research Site | Izhevsk | Russian Federation | 426035 | |
| 251 | Research Site | Moscow | Russian Federation | 115093 | |
| 252 | Research Site | Moscow | Russian Federation | 115522 | |
| 253 | Research Site | St-Petersburg | Russian Federation | 193231 | |
| 254 | Research Site | Jeddah | Saudi Arabia | 21423 | |
| 255 | Research Site | Jeddah | Saudi Arabia | 22252 | |
| 256 | Research Site | Bellville | South Africa | 7530 | |
| 257 | Research Site | Boksburg North | South Africa | 1460 | |
| 258 | Research Site | Cape Town | South Africa | 7570 | |
| 259 | Research Site | Cape Town | South Africa | 7764 | |
| 260 | Research Site | Durban | South Africa | 4001 | |
| 261 | Research Site | Durban | South Africa | 4091 | |
| 262 | Research Site | Durban | South Africa | 4092 | |
| 263 | Research Site | Durban | South Africa | 4450 | |
| 264 | Research Site | Johannesburg | South Africa | 1724 | |
| 265 | Research Site | Johannesburg | South Africa | 1829 | |
| 266 | Research Site | Johannesburg | South Africa | 2113 | |
| 267 | Research Site | Lenasia Ext8 | South Africa | 1820 | |
| 268 | Research Site | Middelburg | South Africa | 1055 | |
| 269 | Research Site | Mowbray | South Africa | 7700 | |
| 270 | Research Site | Parow | South Africa | 7505 | |
| 271 | Research Site | Pretoria | South Africa | 0157 | |
| 272 | Research Site | Umkomaas | South Africa | 4170 | |
| 273 | Research Site | Witbank | South Africa | 1035 | |
| 274 | Research Site | Hsinchu | Taiwan | 300 | |
| 275 | Research Site | Kaohsiung City | Taiwan | 82445 | |
| 276 | Research Site | Kaohsiung Hsien | Taiwan | TAIWAN | |
| 277 | Research Site | Kaohsiung | Taiwan | 80756 | |
| 278 | Research Site | Taichung | Taiwan | 40443 | |
| 279 | Research Site | Tainan City | Taiwan | 70403 | |
| 280 | Research Site | Taipei | Taiwan | 220216 | |
| 281 | Research Site | Taipei | Taiwan | 235 | |
| 282 | Research Site | Yilan | Taiwan | 260 | |
| 283 | Research Site | Ivano-Frankivsk | Ukraine | 76018 | |
| 284 | Research Site | Kharkiv Region | Ukraine | 61075 | |
| 285 | Research Site | London | United Kingdom | SW3 6NP | |
| 286 | Research Site | Ha Noi | Vietnam | 100000 | |
| 287 | Research Site | Hanoi | Vietnam | 100000 | |
| 288 | Research Site | Hanoi | Vietnam | 10000 | |
| 289 | Research Site | Ho Chi Minh | Vietnam | 70000 |
Sponsors and Collaborators
- AstraZeneca
- Amgen
Investigators
- Principal Investigator: Andrew Menzies-Gow, MD, Royal Brompton Hospital, United Kingdom
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03347279
Other Study ID Numbers:
- D5180C00007
First Posted:
Nov 20, 2017
Last Update Posted:
Nov 26, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously | Total of all reporting groups |
| Overall Participants | 528 | 531 | 1059 |
| Age (Count of 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 (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
49.9
(16.3)
|
49.0
(15.9)
|
49.5
(16.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
335
63.4%
|
337
63.5%
|
672
63.5%
|
| Male |
193
36.6%
|
194
36.5%
|
387
36.5%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White |
332
62.9%
|
327
61.6%
|
659
62.2%
|
| Black of African American |
30
5.7%
|
31
5.8%
|
61
5.8%
|
| Asian |
146
27.7%
|
149
28.1%
|
295
27.9%
|
| Native Hawaiian or Other Pacific Islander |
1
0.2%
|
0
0%
|
1
0.1%
|
| American Indian or Alaska Native |
0
0%
|
1
0.2%
|
1
0.1%
|
| Other |
19
3.6%
|
23
4.3%
|
42
4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Hispanic or Latino |
83
15.7%
|
81
15.3%
|
164
15.5%
|
| Not Hispanic or Latino |
445
84.3%
|
450
84.7%
|
895
84.5%
|
Outcome Measures
| Title | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
0.93
|
2.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Negative Binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.37 to 0.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 309 | 309 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
1.02
|
1.73
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Negative Binomial | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Rate Ratio |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 0.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 471 | 453 |
| Least Squares Mean (Standard Error) [Litre] |
0.23
(0.018)
|
0.10
(0.018)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 0.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 480 | 467 |
| Least Squares Mean (Standard Error) [Scale of score] |
1.48
(0.049)
|
1.14
(0.049)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means Difference |
| Estimated Value | 0.33 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 0.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 485 | 472 |
| Least Squares Mean (Standard Error) [Scale of score] |
-1.53
(0.045)
|
-1.20
(0.046)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means Difference |
| Estimated Value | -0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to -0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 374 | 355 |
| Least Squares Mean (Standard Error) [Scale of score] |
-0.70
(0.027)
|
-0.59
(0.027)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tezepelumab 210mg Q4W, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Means Difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to -0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Asthma Exacerbation |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Count of Participants [Participants] |
231
43.8%
|
319
60.1%
|
| Title | Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) |
|---|---|
| Description | Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site |
| Time Frame | From randomisation to Study Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 440 | 426 |
| Least Squares Mean (Standard Error) [ppb] |
-17.29
(1.156)
|
-3.46
(1.165)
|
| Title | Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 439 | 428 |
| Least Squares Mean (Standard Error) [weekly mean rescue medication use] |
-2.53
(0.137)
|
-2.36
(0.137)
|
| Title | Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 185 | 177 |
| Mean (Standard Deviation) [Percentage of work productivity loss] |
-20.16
(30.31)
|
-16.58
(29.46)
|
| Title | Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 15 | 19 |
| Mean (Standard Deviation) [Percentage of class productivity loss] |
-14.03
(33.00)
|
-24.72
(26.48)
|
| Title | Activity Impairment at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 401 | 393 |
| Mean (Standard Deviation) [Percentage of activity impairment] |
-20.0
(28.6)
|
-17.9
(27.1)
|
| Title | Pharmacokinetics of Tezepelumab |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 0 |
| Baseline |
0
(0)
|
|
| Week 4 |
10.1573
(74.51)
|
|
| Week 12 |
18.7396
(48.53)
|
|
| Week 24 |
20.1924
(51.77)
|
|
| Week 36 |
19.5246
(55.58)
|
|
| Week 52 |
19.8894
(70.04)
|
|
| Week 64 |
1.7675
(171.86)
|
| Title | Mean Change From Baseline at Week 52 in EQ-5D-5L VAS |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 448 | 435 |
| Least Squares Mean (Standard Error) [scale of score] |
14.64
(0.708)
|
11.86
(0.712)
|
| Title | Clinicians Global Impression of Change at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 483 | 477 |
| Very much improved |
96
18.2%
|
60
11.3%
|
| Much improved |
199
37.7%
|
132
24.9%
|
| Minimally improved |
98
18.6%
|
131
24.7%
|
| No change |
77
14.6%
|
130
24.5%
|
| Minimally worse |
11
2.1%
|
19
3.6%
|
| Much worse |
2
0.4%
|
4
0.8%
|
| Very much worse |
0
0%
|
1
0.2%
|
| Title | Patients Global Impression of Change at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 479 | 466 |
| Very much improved |
255
48.3%
|
182
34.3%
|
| Much Improved |
103
19.5%
|
94
17.7%
|
| Minimally improved |
71
13.4%
|
76
14.3%
|
| No change |
39
7.4%
|
99
18.6%
|
| Minimally worse |
6
1.1%
|
8
1.5%
|
| Much worse |
4
0.8%
|
6
1.1%
|
| Very much worse |
1
0.2%
|
1
0.2%
|
| Title | Patients Global Impression of Severity at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 479 | 466 |
| No symptoms |
118
22.3%
|
78
14.7%
|
| Very mild symptoms |
138
26.1%
|
128
24.1%
|
| Mild symptoms |
110
20.8%
|
128
24.1%
|
| Moderate symptoms |
99
18.8%
|
111
20.9%
|
| Severe symptoms |
14
2.7%
|
19
3.6%
|
| Very severe symptoms |
0
0%
|
2
0.4%
|
| Title | Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) |
|---|---|
| Description | Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL) |
| Time Frame | From randomisation to Study Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 458 | 451 |
| Least Squares Mean (Standard Error) [cells/uL] |
-170.02
(9.222)
|
-40.15
(9.254)
|
| Title | Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) |
|---|---|
| Description | Mean change from baseline at Study Week 52 in total serum IgE (IU/mL) |
| Time Frame | From randomisation to Study Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 482 | 471 |
| Least Squares Mean (Standard Error) [IU/mL] |
-164.38
(34.414)
|
43.61
(34.542)
|
| Title | Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Hospitalisation |
17
3.2%
|
37
7%
|
| Emergency Room visit |
23
4.4%
|
50
9.4%
|
| Unscheduled visit to specialist |
187
35.4%
|
231
43.5%
|
| Home visit |
9
1.7%
|
10
1.9%
|
| Telephone call |
101
19.1%
|
133
25%
|
| Ambulance transport |
4
0.8%
|
12
2.3%
|
| Title | Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 414 | 391 |
| Least Squares Mean (Standard Error) [L/min] |
34.57
(3.051)
|
18.01
(3.074)
|
| Title | Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 405 | 390 |
| Least Squares Mean (Standard Error) [L/min] |
23.87
(3.075)
|
9.01
(3.094)
|
| Title | Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 418 | 395 |
| Least Squares Mean (Standard Error) [percentage of nights with awakenings] |
-33.51
(1.381)
|
-30.22
(1.387)
|
| Title | Immunogenecity of Tezepelumab |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 527 | 530 |
| ADA positive at baseline and/or post-baseline |
26
4.9%
|
44
8.3%
|
| Any baseline ADA positive |
17
3.2%
|
25
4.7%
|
| Only baseline ADA positive |
14
2.7%
|
8
1.5%
|
| Any post-baseline ADA positive |
12
2.3%
|
36
6.8%
|
| Both baseline and >= 1 post-baseline ADA positive |
3
0.6%
|
17
3.2%
|
| Treatment induced ADA positive |
9
1.7%
|
18
3.4%
|
| Treatment boosted ADA positive |
1
0.2%
|
2
0.4%
|
| Treatment emergent ADA positive |
10
1.9%
|
20
3.8%
|
| ADA persistently positive |
4
0.8%
|
18
3.4%
|
| ADA transiently positive |
8
1.5%
|
18
3.4%
|
| Title | Proportion of Subjects Who Had no Asthma Exacerbations |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Number [Percentage] |
54.2
|
38.6
|
| Title | Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
0.06
|
0.28
|
| Title | Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Number [Percentage] |
4.7
|
12.2
|
| Title | Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Number [Percentage] |
92.4
|
85.1
|
| Title | Annual Asthma Exacerbation Rate Associated With Hospitalisations |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
0.03
|
0.19
|
| Title | Annual Asthma Exacerbation Rate Using Adjudicated Data |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
0.94
|
2.14
|
| Title | Annual Asthma Exacerbation Rate Associated With Emergency Room (ER) Visit or Hospitalisation Using Adjudicated Data |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo |
|---|---|---|
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously |
| Measure Participants | 528 | 531 |
| Least Squares Mean (95% Confidence Interval) [events per year] |
0.08
|
0.31
|
Adverse Events
| Time Frame | From first dose of study drug until end of study at Week 64. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Tezepelumab 210mg Q4W | Placebo | ||
| Arm/Group Description | Tezepelumab administered every 4 weeks subcutaneously | Placebo administered subcutaneously | ||
All Cause Mortality |
||||
| Tezepelumab 210mg Q4W | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/528 (0%) | 2/531 (0.4%) | ||
Serious Adverse Events |
||||
| Tezepelumab 210mg Q4W | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/528 (9.8%) | 73/531 (13.7%) | ||
| Cardiac disorders | ||||
| Aortic valve stenosis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Cardiac failure | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Cardiac failure congestive | 2/528 (0.4%) | 2 | 0/531 (0%) | 0 |
| Coronary artery disease | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Coronary artery occlusion | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Ventricular extrasystoles | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Hypertrophic cardiomyopathy | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo positional | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Eye disorders | ||||
| Cataract | 1/528 (0.2%) | 2 | 1/531 (0.2%) | 1 |
| Uveitis | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Colitis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Colitis ischaemic | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Diverticular perforation | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Inguinal hernia | 0/528 (0%) | 0 | 1/531 (0.2%) | 2 |
| Obstruction gastric | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Oesophageal achalasia | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pancreatitis acute | 0/528 (0%) | 0 | 1/531 (0.2%) | 3 |
| Pancreatitis necrotising | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Rectal haemorrhage | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Umbilical hernia | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 1 |
| General disorders | ||||
| Death | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Non-cardiac chest pain | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis chronic | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Cholelithiasis | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 1 |
| Immune system disorders | ||||
| Anaphylactic reaction | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Infections and infestations | ||||
| Anal abscess | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Atypical pneumonia | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Breast abscess | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Cellulitis | 0/528 (0%) | 0 | 2/531 (0.4%) | 2 |
| Diverticulitis | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 1 |
| Gastroenteritis | 0/528 (0%) | 0 | 2/531 (0.4%) | 2 |
| Gastroenteritis salmonella | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Gastroenteritis viral | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Herpes zoster oticus | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Influenza | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Lower respiratory tract infection | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Lower respiratory tract infection bacterial | 0/528 (0%) | 0 | 2/531 (0.4%) | 4 |
| Lung abscess | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pneumonia bacterial | 2/528 (0.4%) | 2 | 2/531 (0.4%) | 2 |
| Pneumonia klebsiella | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pneumonia streptococcal | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pneumonia viral | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Upper respiratory tract infection | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Viral upper respiratory tract infection | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Covid-19 | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Osteomyelitis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Pneumonia | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 1 |
| Septic shock | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Hip fracture | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Incisional hernia | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Ligament rupture | 2/528 (0.4%) | 2 | 0/531 (0%) | 0 |
| Ligament sprain | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Lumbar vertebral fracture | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Radius fracture | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Road traffic accident | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Skin laceration | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Tendon rupture | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Tibia fracture | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Ulna fracture | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Head injury | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Investigations | ||||
| Blood creatine phosphokinase increased | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus inadequate control | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Diabetic ketoacidosis | 0/528 (0%) | 0 | 1/531 (0.2%) | 2 |
| Gout | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Type 1 diabetes mellitus | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Type 2 diabetes mellitus | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Bone cyst | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Myositis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Osteoarthritis | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 1 |
| Polyarthritis | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Spinal stenosis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Lumbar spinal stenosis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Muscle necrosis | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/528 (0.2%) | 1 | 2/531 (0.4%) | 2 |
| Benign neoplasm of thyroid gland | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Colon adenoma | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Endometrial cancer | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Malignant melanoma in situ | 2/528 (0.4%) | 2 | 0/531 (0%) | 0 |
| Prostate cancer | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Squamous cell carcinoma | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Squamous cell carcinoma of the oral cavity | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Nervous system disorders | ||||
| Cubital tunnel syndrome | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Haemorrhagic stroke | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Idiopathic generalised epilepsy | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Migraine | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Myelopathy | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Transient ischaemic attack | 1/528 (0.2%) | 1 | 1/531 (0.2%) | 2 |
| Seizure | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 2/528 (0.4%) | 2 | 0/531 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Ureterolithiasis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Ovarian cyst | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 14/528 (2.7%) | 15 | 39/531 (7.3%) | 81 |
| Eosinophilic pneumonia | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Epistaxis | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Nasal polyps | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Pulmonary embolism | 0/528 (0%) | 0 | 1/531 (0.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis contact | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Vascular disorders | ||||
| Cyanosis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
| Thrombosis | 1/528 (0.2%) | 1 | 0/531 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Tezepelumab 210mg Q4W | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 306/528 (58%) | 331/531 (62.3%) | ||
| General disorders | ||||
| Influenza like illness | 19/528 (3.6%) | 21 | 22/531 (4.1%) | 26 |
| Infections and infestations | ||||
| Bronchitis bacterial | 24/528 (4.5%) | 26 | 17/531 (3.2%) | 20 |
| Urinary tract infection | 22/528 (4.2%) | 33 | 22/531 (4.1%) | 24 |
| Viral upper respiratory tract infection | 17/528 (3.2%) | 21 | 13/531 (2.4%) | 18 |
| Bronchitis | 25/528 (4.7%) | 39 | 33/531 (6.2%) | 36 |
| Gastroenteritis | 17/528 (3.2%) | 18 | 14/531 (2.6%) | 15 |
| Nasopharyngitis | 113/528 (21.4%) | 172 | 114/531 (21.5%) | 188 |
| Pharyngitis | 17/528 (3.2%) | 18 | 15/531 (2.8%) | 17 |
| Rhinitis | 14/528 (2.7%) | 18 | 17/531 (3.2%) | 37 |
| Sinusitis | 19/528 (3.6%) | 22 | 40/531 (7.5%) | 56 |
| Upper respiratory tract infection | 58/528 (11%) | 94 | 88/531 (16.6%) | 129 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 20/528 (3.8%) | 25 | 13/531 (2.4%) | 14 |
| Back pain | 21/528 (4%) | 26 | 15/531 (2.8%) | 16 |
| Nervous system disorders | ||||
| Headache | 43/528 (8.1%) | 96 | 45/531 (8.5%) | 68 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 14/528 (2.7%) | 17 | 23/531 (4.3%) | 25 |
| Rhinitis allergic | 16/528 (3%) | 19 | 17/531 (3.2%) | 25 |
| Vascular disorders | ||||
| Hypertension | 23/528 (4.4%) | 27 | 22/531 (4.1%) | 29 |
Limitations/Caveats
[Not Specified]
More Information
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
| Name/Title | Global Clinical Head |
|---|---|
| Organization | AstraZeneca |
| Phone | +1 302 885 1180 |
| information.center@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03347279
Other Study ID Numbers:
- D5180C00007
First Posted:
Nov 20, 2017
Last Update Posted:
Nov 26, 2021
Last Verified:
Oct 1, 2021