Study to Evaluate Tezepelumab on Airway Inflammation in Adults with Uncontrolled Asthma (CASCADE)  (CASCADE)

Recruitment Status:
Completed

Sponsor:
AstraZeneca

Collaborator:
Amgen

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT03688074

Verification:
Verified 01 February 2022   by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled asthma.

Official Title:A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Tezepelumab on Airway Inflammation in Adults with Inadequately Controlled Asthma on Inhaled Corticosteroids and at least one additional asthma controller (CASCADE)
Study Type:Interventional
Overall Recruitment Status:Completed
Study Start Date:02 November 2018
Study Start Date Type:Actual
Primary Completion Date:16 November 2020
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking Description: Double-blind
Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
ConditionInterventionPhase
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Biological/Vaccine: Tezepelumab
Other: Placebo
Phase 2
Ages Eligible for Study: 18 Years  to 75 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
- Subject must be 18 to 75 years of age.
- 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; must be stable for at least 3 months prior to screening visit.
- 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.
-At enrolment, the subject must have a predicted normal value for the morning pre-bronchodilator FEV1>50% and more than 1L.
- Evidence of asthma as documented by reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months prior to screening, or during the screening period prior to randomization.
- ACQ-6 score ≥ 1.5 during the screening period prior to randomization.

Principal Exclusion Criteria:
- Any clinically important pulmonary disease other than asthma.
- History of cancer.
- Hospitalization or required OCS for asthma exacerbation within 6 weeks of enrolment or >3 exacerbations requiring OCS or hospitalization in the year prior to visit 1 or who had been intubated or admitted to ICU for asthma exacerbation in the year prior to enrolment.
- History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalized <2 weeks before visit 1 or during the run-in period.
- Current smokers or subjects with smoking history ≥10 pack-yrs, including e-cigarettes. Former smokers with a smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit 1, including e-cigarette use.
- History of chronic alcohol or drug abuse within 12 months prior to visit 1.
-Tuberculosis requiring treatment within 12 months prior to visit 1.
- History of known immunodeficiency disorder including a positive HIV test at visit 1, or the subject is taking antiretroviral medications as determined by medical history and/or subject's verbal report.
- History of anaphylaxis or documented immune complex disease (type III hypersensitivity reactions) following any biologic therapy
Subject randomized in a previous Tezepelumab study or in a current study with another investigational product.
-Pregnant, breastfeeding or lactating women.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca
Amgen

Investigators

Principal Investigator: Chris  Brightling   University of Leicester, United Kingdom

Locations

CountryLocationFacilityContactStatus
Canada , ABResearch Site Calgary, AB, Canada, T2N 4Z6Completed
Canada , BCResearch Site Vancouver, BC, Canada, V5Z 1M9Completed
United States of America , TXResearch Site Galveston, TX, United States of America, 77555Completed
United States of America , MAResearch Site Boston, MA, United States of America, 02115Completed
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Completed
GermanyResearch Site Frankfurt, Germany, 60596Completed
GermanyResearch Site Frankfurt/Main, Germany, 60389Completed
GermanyResearch Site Grosshansdorf, Germany, 22927Completed
GermanyResearch Site Landsberg, Germany, 86899Completed
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQCompleted
United KingdomResearch Site Headington, United Kingdom, OX3 9DUCompleted
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPCompleted
United KingdomResearch Site Liverpool, United Kingdom, L7 8XPWithdrawn
United KingdomResearch Site London, United Kingdom, W1G 8HUCompleted
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBCompleted
United KingdomResearch Site Wythenshawe, United Kingdom, M23 9QZCompleted
United States of America , COResearch Site Denver, CO, United States of America, 80206Completed
United States of America , CTResearch Site New Haven, CT, United States of America, 06510Completed
Canada , QCResearch Site Montreal, QC, Canada, H4A 3J1Completed
Canada , QCResearch Site Quebec, QC, Canada, G1V 4G5Completed
DenmarkResearch Site Aarhus N, Denmark, 8200Completed
DenmarkResearch Site Ålborg, Denmark, 9000Completed
DenmarkResearch Site Hvidovre, Denmark, 2650Completed
DenmarkResearch Site København NV, Denmark, 2400Completed
DenmarkResearch Site Naestved, Denmark, 4700Completed
DenmarkResearch Site Odense C, Denmark, 5000Completed
DenmarkResearch Site Vejle, Denmark, 7100Completed
Canada , ONResearch Site Hamilton, ON, Canada, L8N 3Z5Completed
Canada , ONResearch Site Ottawa, ON, Canada, K1H 8L6Completed

 File nameDescription
Statistical Analysis Plan (SAP)Statistical Analysis Plan (SAP)
CSPCSP

Participant Flow


Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
116 subjects randomized to Tezepelumab 210 mg Q4W or Placebo in 1:1 treatment allocation. All randomized subjects were treated.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study randomized subjects across the spectrum of T2 status. Randomization was stratified by screening blood eosinophil level (<150 , 150 - <300, >=300 cells/µL).

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Participant Flow:   Overall Study

 Teze 210 mg Q4WPlacebo
 STARTED 5957
 COMPLETED 5856
 NOT COMPLETED 11
  Adverse Event  01
  Other  10

Baseline Characteristics


Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
Full Analysis Set - Include all subjects randomised to study treatment who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Baseline Measures

 Teze 210 mg Q4WPlaceboTotal
Number of Participants
[units: Participants]
5957116
Age Continuous  [1]
[units: Years]
Mean ± Standard Deviation
50.4 ± 12.750.4 ± 13.950.4 ± 13.2
Age Categorical  [2]
[units: Participants]
   
<=18 years000
Between 18 and 65 years5149100
>=65 years8816
Sex: Female, Male  [3]
[units: Participants]
   
Female392665
Male203151
Race/Ethnicity, Customized  [4]
[units: Participants]
   
White5455109
Black or African American213
Asian213
Other (includes Native Hawaiian or Other Pacific Islander and American Indian or Alaska Native)101
Race/Ethnicity, Customized  [5]
[units: Participants]
   
Hispanic or Latino000
Not Hispanic or Latino5957116

Outcome Measures


1. Primary Outcome Measure: Airway submucosal inflammatory cells ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypePrimary
Measure NameAirway submucosal inflammatory cells ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to end of treatment (EOT) expressed as a ratio i.e. (EOT/baseline) in numbers of each of the airway submucosal inflammatory cells, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
5456
Airway submucosal inflammatory cells ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
  
Eosinophils0.11 (0.06 to 0.21) 0.75 (0.41 to 1.38)
Neutrophils1.11 (0.88 to 1.39) 0.81 (0.66 to 1.01)
T cells CD3+0.91 (0.78 to 1.07) 0.81 (0.70 to 0.95)
T cells CD4+0.96 (0.82 to 1.14) 0.81 (0.70 to 0.95)
Mast cells Tryptase+0.84 (0.70 to 1.02) 1.01 (0.84 to 1.22)
Mast cells Chymase+1.07 (0.76 to 1.52) 0.90 (0.65 to 1.26)

Statistical Analysis 1 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] <0.001
Other  [5] 0.15
90% Confidence Interval( 0.06 to 0.35 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter : Eosinophils (cells/mm^2)

Statistical Analysis 2 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.106
Other  [5] 1.36
90% Confidence Interval( 0.99 to 1.86 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Neutrophils (cells/mm^2)

Statistical Analysis 3 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.389
Other  [5] 1.12
90% Confidence Interval( 0.90 to 1.40 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: T cells CD3+ (cells/mm^2)

Statistical Analysis 4 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.216
Other  [5] 1.18
90% Confidence Interval( 0.94 to 1.48 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: T cells CD4+ (cells/mm^2)

Statistical Analysis 5 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.260
Other  [5] 0.83
90% Confidence Interval( 0.64 to 1.09 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Mast cells Tryptase+ (cells/mm^2)

Statistical Analysis 6 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.546
Other  [5] 1.19
90% Confidence Interval( 0.74 to 1.92 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Mast cells Chymase+ (cells/mm^2)

2. Secondary Outcome Measure: Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypeSecondary
Measure NameReticular basement membrane (RBM) thickness ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects randomised to study treatment who completed at least 20 weeks of study treatment and had a baseline assessment and an EOT assessment not greater than 8 weeks after date of last dose of IP.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
4240
Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
0.87 (0.79 to 0.95) 0.90 (0.81 to 0.99)

No statistical analysis provided for Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.

3. Secondary Outcome Measure: Percent (%) airway epithelial integrity ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypeSecondary
Measure NamePercent (%) airway epithelial integrity ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
5456
Percent (%) airway epithelial integrity ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
  
Intact epithelium0.87 (0.61 to 1.23) 0.84 (0.59 to 1.19)
Damaged epithelium1.01 (0.92 to 1.12) 0.95 (0.86 to 1.04)
Denuded epithelium1.05 (0.83 to 1.31) 1.34 (1.07 to 1.68)

No statistical analysis provided for Percent (%) airway epithelial integrity ratio change from baseline to EOT.

Serious Adverse Events


Time FrameFrom first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Additional DescriptionNo text entered.

Reporting Groups

 Description
PlaceboPlacebo subcutaneous injection
Teze 210 mg Q4WTezepelumab subcutaneous injection

Serious Adverse Events

 PlaceboTeze 210 mg Q4W
Total, serious adverse events   
# participants affected / at risk 7/57 (12.28%)3/59 (5.08%)
Cardiac disorders  
Myocarditis1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Gastrointestinal disorders  
Abdominal pain1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Gastrointestinal disorders  
Gastrooesophageal reflux disease1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Gastrointestinal disorders  
Hiatus hernia1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Infections and infestations  
Influenza1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Injury, poisoning and procedural complications  
Post procedural complication1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Meningioma1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Pancreatic carcinoma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Squamous cell carcinoma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Renal and urinary disorders  
Urinary retention1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Respiratory, thoracic and mediastinal disorders  
Asthma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA 23.1

Other Adverse Events


Time FrameFrom first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Additional DescriptionNo text entered.

Frequency Threshold

Threshold above which other adverse events are reported 3%

Reporting Groups

 Description
PlaceboPlacebo subcutaneous injection
Teze 210 mg Q4WTezepelumab subcutaneous injection

Other Adverse Events

 PlaceboTeze 210 mg Q4W
Total, other (not including serious) adverse events   
# participants affected / at risk 45/57 (78.95%)48/59 (81.36%)
Eye disorders  
Dry eye1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Gastrointestinal disorders  
Diarrhoea1, †  
# participants affected / at risk 0/57 (0.00%)5/59 (8.47%)
# events06
Gastrointestinal disorders  
Nausea1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Gastrointestinal disorders  
Vomiting1, †  
# participants affected / at risk 3/57 (5.26%)2/59 (3.39%)
# events32
General disorders and administration site conditions  
Influenza like illness1, †  
# participants affected / at risk 3/57 (5.26%)3/59 (5.08%)
# events33
General disorders and administration site conditions  
Injection site erythema1, †  
# participants affected / at risk 2/57 (3.51%)5/59 (8.47%)
# events1214
General disorders and administration site conditions  
Injection site granuloma1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
General disorders and administration site conditions  
Injection site pruritus1, †  
# participants affected / at risk 1/57 (1.75%)4/59 (6.78%)
# events15
General disorders and administration site conditions  
Oedema peripheral1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
General disorders and administration site conditions  
Pyrexia1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
Infections and infestations  
Bronchitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Candida infection1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Chronic sinusitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Infections and infestations  
Conjunctivitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Gastroenteritis1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Lower respiratory tract infection1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events12
Infections and infestations  
Lower respiratory tract infection bacterial1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Nasopharyngitis1, †  
# participants affected / at risk 21/57 (36.84%)22/59 (37.29%)
# events2228
Infections and infestations  
Oral candidiasis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events04
Infections and infestations  
Pneumonia1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events12
Infections and infestations  
Rhinitis1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Sinusitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Infections and infestations  
Tonsillitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Upper respiratory tract infection1, †  
# participants affected / at risk 4/57 (7.02%)3/59 (5.08%)
# events43
Infections and infestations  
Urinary tract infection1, †  
# participants affected / at risk 2/57 (3.51%)3/59 (5.08%)
# events54
Injury, poisoning and procedural complications  
Contusion1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events05
Injury, poisoning and procedural complications  
Fall1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events14
Injury, poisoning and procedural complications  
Post procedural complication1, †  
# participants affected / at risk 10/57 (17.54%)11/59 (18.64%)
# events1211
Injury, poisoning and procedural complications  
Post procedural fever1, †  
# participants affected / at risk 2/57 (3.51%)4/59 (6.78%)
# events24
Injury, poisoning and procedural complications  
Procedural pain1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
Musculoskeletal and connective tissue disorders  
Arthralgia1, †  
# participants affected / at risk 3/57 (5.26%)3/59 (5.08%)
# events43
Musculoskeletal and connective tissue disorders  
Back pain1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Musculoskeletal and connective tissue disorders  
Bursitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Musculoskeletal and connective tissue disorders  
Musculoskeletal chest pain1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events31
Musculoskeletal and connective tissue disorders  
Myalgia1, †  
# participants affected / at risk 1/57 (1.75%)3/59 (5.08%)
# events13
Nervous system disorders  
Headache1, †  
# participants affected / at risk 8/57 (14.04%)6/59 (10.17%)
# events89
Respiratory, thoracic and mediastinal disorders  
Cough1, †  
# participants affected / at risk 4/57 (7.02%)6/59 (10.17%)
# events59
Respiratory, thoracic and mediastinal disorders  
Dysphonia1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Respiratory, thoracic and mediastinal disorders  
Nasal congestion1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Respiratory, thoracic and mediastinal disorders  
Oropharyngeal pain1, †  
# participants affected / at risk 2/57 (3.51%)6/59 (10.17%)
# events26
Vascular disorders  
Hypertension1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA 23.1

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description: 

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:Globall Clinical Head
Organization:AstraZeneca
Phone+1 877-240-9479 
E-mail:[email protected]
.

Purpose

A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled asthma.

Official Title:A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Tezepelumab on Airway Inflammation in Adults with Inadequately Controlled Asthma on Inhaled Corticosteroids and at least one additional asthma controller (CASCADE)
Study Type:Interventional
Overall Recruitment Status:Completed
Study Start Date:02 November 2018
Study Start Date Type:Actual
Primary Completion Date:16 November 2020
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking Description: Double-blind
Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
ConditionInterventionPhase
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Biological/Vaccine: Tezepelumab
Other: Placebo
Phase 2
Ages Eligible for Study: 18 Years  to 75 Years
Genders Eligible for Study: Both
Gender Based: No
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:
- Subject must be 18 to 75 years of age.
- 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; must be stable for at least 3 months prior to screening visit.
- 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.
-At enrolment, the subject must have a predicted normal value for the morning pre-bronchodilator FEV1>50% and more than 1L.
- Evidence of asthma as documented by reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months prior to screening, or during the screening period prior to randomization.
- ACQ-6 score ≥ 1.5 during the screening period prior to randomization.

Principal Exclusion Criteria:
- Any clinically important pulmonary disease other than asthma.
- History of cancer.
- Hospitalization or required OCS for asthma exacerbation within 6 weeks of enrolment or >3 exacerbations requiring OCS or hospitalization in the year prior to visit 1 or who had been intubated or admitted to ICU for asthma exacerbation in the year prior to enrolment.
- History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalized <2 weeks before visit 1 or during the run-in period.
- Current smokers or subjects with smoking history ≥10 pack-yrs, including e-cigarettes. Former smokers with a smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit 1, including e-cigarette use.
- History of chronic alcohol or drug abuse within 12 months prior to visit 1.
-Tuberculosis requiring treatment within 12 months prior to visit 1.
- History of known immunodeficiency disorder including a positive HIV test at visit 1, or the subject is taking antiretroviral medications as determined by medical history and/or subject's verbal report.
- History of anaphylaxis or documented immune complex disease (type III hypersensitivity reactions) following any biologic therapy
Subject randomized in a previous Tezepelumab study or in a current study with another investigational product.
-Pregnant, breastfeeding or lactating women.


Contacts

Contact: AstraZeneca Clinical  Study Information Center   1-877-240-9479    [email protected]  

Sponsors and Collaborators

AstraZeneca
Amgen

Investigators

Principal Investigator: Chris  Brightling   University of Leicester, United Kingdom

Locations

CountryLocationFacilityContactStatus
Canada , ABResearch Site Calgary, AB, Canada, T2N 4Z6Completed
Canada , BCResearch Site Vancouver, BC, Canada, V5Z 1M9Completed
United States of America , TXResearch Site Galveston, TX, United States of America, 77555Completed
United States of America , MAResearch Site Boston, MA, United States of America, 02115Completed
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Completed
GermanyResearch Site Frankfurt, Germany, 60596Completed
GermanyResearch Site Frankfurt/Main, Germany, 60389Completed
GermanyResearch Site Grosshansdorf, Germany, 22927Completed
GermanyResearch Site Landsberg, Germany, 86899Completed
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQCompleted
United KingdomResearch Site Headington, United Kingdom, OX3 9DUCompleted
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPCompleted
United KingdomResearch Site Liverpool, United Kingdom, L7 8XPWithdrawn
United KingdomResearch Site London, United Kingdom, W1G 8HUCompleted
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBCompleted
United KingdomResearch Site Wythenshawe, United Kingdom, M23 9QZCompleted
United States of America , COResearch Site Denver, CO, United States of America, 80206Completed
United States of America , CTResearch Site New Haven, CT, United States of America, 06510Completed
Canada , QCResearch Site Montreal, QC, Canada, H4A 3J1Completed
Canada , QCResearch Site Quebec, QC, Canada, G1V 4G5Completed
DenmarkResearch Site Aarhus N, Denmark, 8200Completed
DenmarkResearch Site Ålborg, Denmark, 9000Completed
DenmarkResearch Site Hvidovre, Denmark, 2650Completed
DenmarkResearch Site København NV, Denmark, 2400Completed
DenmarkResearch Site Naestved, Denmark, 4700Completed
DenmarkResearch Site Odense C, Denmark, 5000Completed
DenmarkResearch Site Vejle, Denmark, 7100Completed
Canada , ONResearch Site Hamilton, ON, Canada, L8N 3Z5Completed
Canada , ONResearch Site Ottawa, ON, Canada, K1H 8L6Completed

Oversight


Is IND/IDE protocol: Yes 
IND/IDE Grantor: CDER 
IND/IDE Number: 103031 
IND/IDE Serial Number: 0124 
Has Expanded Access: Unknown 
U.S. FDA-regulated Drug: Yes 
U.S. FDA-regulated Device: No 
Product Exported From U.S.: Yes 

More Information


Statistical Analysis Plan (SAP)

CSP

No publications provided

Responsible Party:AstraZeneca
ClinicalTrials.gov Identifier:NCT03688074
Other Study ID Numbers:D5180C00013

Keywords provided by AstraZeneca
Asthma
Uncontrolled asthma
Severe uncontrolled asthma

Additional Relevant MeSH terms:
AsthmaBronchial Diseases
Respiratory Tract DiseasesLung Diseases, Obstructive
Lung DiseasesRespiratory Hypersensitivity
Hypersensitivity, ImmediateHypersensitivity
Immune System Diseases

Participant Flow


Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
116 subjects randomized to Tezepelumab 210 mg Q4W or Placebo in 1:1 treatment allocation. All randomized subjects were treated.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study randomized subjects across the spectrum of T2 status. Randomization was stratified by screening blood eosinophil level (<150 , 150 - <300, >=300 cells/µL).

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Participant Flow:   Overall Study

 Teze 210 mg Q4WPlacebo
 STARTED 5957
 COMPLETED 5856
 NOT COMPLETED 11
  Adverse Event  01
  Other  10

Baseline Characteristics


Analysis Population Description -- Explanation of how the number of participants for analysis was determined.
Full Analysis Set - Include all subjects randomised to study treatment who received at least one dose of IP, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Baseline Measures

 Teze 210 mg Q4WPlaceboTotal
Number of Participants
[units: Participants]
5957116
Age Continuous  [1]
[units: Years]
Mean ± Standard Deviation
50.4 ± 12.750.4 ± 13.950.4 ± 13.2
Age Categorical  [2]
[units: Participants]
   
<=18 years000
Between 18 and 65 years5149100
>=65 years8816
Sex: Female, Male  [3]
[units: Participants]
   
Female392665
Male203151
Race/Ethnicity, Customized  [4]
[units: Participants]
   
White5455109
Black or African American213
Asian213
Other (includes Native Hawaiian or Other Pacific Islander and American Indian or Alaska Native)101
Race/Ethnicity, Customized  [5]
[units: Participants]
   
Hispanic or Latino000
Not Hispanic or Latino5957116

Outcome Measures


1. Primary Outcome Measure: Airway submucosal inflammatory cells ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypePrimary
Measure NameAirway submucosal inflammatory cells ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to end of treatment (EOT) expressed as a ratio i.e. (EOT/baseline) in numbers of each of the airway submucosal inflammatory cells, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
5456
Airway submucosal inflammatory cells ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
  
Eosinophils0.11 (0.06 to 0.21) 0.75 (0.41 to 1.38)
Neutrophils1.11 (0.88 to 1.39) 0.81 (0.66 to 1.01)
T cells CD3+0.91 (0.78 to 1.07) 0.81 (0.70 to 0.95)
T cells CD4+0.96 (0.82 to 1.14) 0.81 (0.70 to 0.95)
Mast cells Tryptase+0.84 (0.70 to 1.02) 1.01 (0.84 to 1.22)
Mast cells Chymase+1.07 (0.76 to 1.52) 0.90 (0.65 to 1.26)

Statistical Analysis 1 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] <0.001
Other  [5] 0.15
90% Confidence Interval( 0.06 to 0.35 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter : Eosinophils (cells/mm^2)

Statistical Analysis 2 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.106
Other  [5] 1.36
90% Confidence Interval( 0.99 to 1.86 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Neutrophils (cells/mm^2)

Statistical Analysis 3 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.389
Other  [5] 1.12
90% Confidence Interval( 0.90 to 1.40 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: T cells CD3+ (cells/mm^2)

Statistical Analysis 4 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.216
Other  [5] 1.18
90% Confidence Interval( 0.94 to 1.48 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: T cells CD4+ (cells/mm^2)

Statistical Analysis 5 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.260
Other  [5] 0.83
90% Confidence Interval( 0.64 to 1.09 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Mast cells Tryptase+ (cells/mm^2)

Statistical Analysis 6 for Airway submucosal inflammatory cells ratio change from baseline to EOT.

Groups  [1] All groups
Method  [3] ANCOVA
P-Value  [4] 0.546
Other  [5] 1.19
90% Confidence Interval( 0.74 to 1.92 )
[1]  Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[3]  Other relevant information, such as adjustments or degrees of freedom:
 Model includes treatment+log transformed baseline value+stratification factor (screening eos count [<150, 150-<300, >=300 cells/uL])
[4]  Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
 Nominal p-values were reported. No adjustment of multiplicity was performed.
[5]  Other relevant estimation information:
 Parameter: Mast cells Chymase+ (cells/mm^2)

2. Secondary Outcome Measure: Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypeSecondary
Measure NameReticular basement membrane (RBM) thickness ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects randomised to study treatment who completed at least 20 weeks of study treatment and had a baseline assessment and an EOT assessment not greater than 8 weeks after date of last dose of IP.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
4240
Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
0.87 (0.79 to 0.95) 0.90 (0.81 to 0.99)

No statistical analysis provided for Reticular basement membrane (RBM) thickness ratio change from baseline to EOT.

3. Secondary Outcome Measure: Percent (%) airway epithelial integrity ratio change from baseline to EOT.   [ Time Frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic). ]

Measure TypeSecondary
Measure NamePercent (%) airway epithelial integrity ratio change from baseline to EOT.
Measure DescriptionThe change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.
Time FrameFirst dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Safety Issue?No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

Reporting Groups

 Description
Teze 210 mg Q4WTezepelumab subcutaneous injection
PlaceboPlacebo subcutaneous injection

Measured Values

 Teze 210 mg Q4WPlacebo
Number of Participants Analyzed
[units:participants]
5456
Percent (%) airway epithelial integrity ratio change from baseline to EOT.
[units: Ratio]
Geometric Least Squares Mean (90% Confidence Interval)
  
Intact epithelium0.87 (0.61 to 1.23) 0.84 (0.59 to 1.19)
Damaged epithelium1.01 (0.92 to 1.12) 0.95 (0.86 to 1.04)
Denuded epithelium1.05 (0.83 to 1.31) 1.34 (1.07 to 1.68)

No statistical analysis provided for Percent (%) airway epithelial integrity ratio change from baseline to EOT.

Serious Adverse Events


Time FrameFrom first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Additional DescriptionNo text entered.

Reporting Groups

 Description
PlaceboPlacebo subcutaneous injection
Teze 210 mg Q4WTezepelumab subcutaneous injection

Serious Adverse Events

 PlaceboTeze 210 mg Q4W
Total, serious adverse events   
# participants affected / at risk 7/57 (12.28%)3/59 (5.08%)
Cardiac disorders  
Myocarditis1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Gastrointestinal disorders  
Abdominal pain1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Gastrointestinal disorders  
Gastrooesophageal reflux disease1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Gastrointestinal disorders  
Hiatus hernia1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Infections and infestations  
Influenza1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Injury, poisoning and procedural complications  
Post procedural complication1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Meningioma1, †  
# participants affected / at risk 0/57 (0.00%)1/59 (1.69%)
# events01
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Pancreatic carcinoma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  
Squamous cell carcinoma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Renal and urinary disorders  
Urinary retention1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Respiratory, thoracic and mediastinal disorders  
Asthma1, †  
# participants affected / at risk 1/57 (1.75%)0/59 (0.00%)
# events10
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA 23.1

Other Adverse Events


Time FrameFrom first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Additional DescriptionNo text entered.

Frequency Threshold

Threshold above which other adverse events are reported 3%

Reporting Groups

 Description
PlaceboPlacebo subcutaneous injection
Teze 210 mg Q4WTezepelumab subcutaneous injection

Other Adverse Events

 PlaceboTeze 210 mg Q4W
Total, other (not including serious) adverse events   
# participants affected / at risk 45/57 (78.95%)48/59 (81.36%)
Eye disorders  
Dry eye1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Gastrointestinal disorders  
Diarrhoea1, †  
# participants affected / at risk 0/57 (0.00%)5/59 (8.47%)
# events06
Gastrointestinal disorders  
Nausea1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Gastrointestinal disorders  
Vomiting1, †  
# participants affected / at risk 3/57 (5.26%)2/59 (3.39%)
# events32
General disorders and administration site conditions  
Influenza like illness1, †  
# participants affected / at risk 3/57 (5.26%)3/59 (5.08%)
# events33
General disorders and administration site conditions  
Injection site erythema1, †  
# participants affected / at risk 2/57 (3.51%)5/59 (8.47%)
# events1214
General disorders and administration site conditions  
Injection site granuloma1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
General disorders and administration site conditions  
Injection site pruritus1, †  
# participants affected / at risk 1/57 (1.75%)4/59 (6.78%)
# events15
General disorders and administration site conditions  
Oedema peripheral1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
General disorders and administration site conditions  
Pyrexia1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
Infections and infestations  
Bronchitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Candida infection1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Chronic sinusitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Infections and infestations  
Conjunctivitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Gastroenteritis1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Lower respiratory tract infection1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events12
Infections and infestations  
Lower respiratory tract infection bacterial1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Nasopharyngitis1, †  
# participants affected / at risk 21/57 (36.84%)22/59 (37.29%)
# events2228
Infections and infestations  
Oral candidiasis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events04
Infections and infestations  
Pneumonia1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events12
Infections and infestations  
Rhinitis1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Infections and infestations  
Sinusitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Infections and infestations  
Tonsillitis1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events02
Infections and infestations  
Upper respiratory tract infection1, †  
# participants affected / at risk 4/57 (7.02%)3/59 (5.08%)
# events43
Infections and infestations  
Urinary tract infection1, †  
# participants affected / at risk 2/57 (3.51%)3/59 (5.08%)
# events54
Injury, poisoning and procedural complications  
Contusion1, †  
# participants affected / at risk 0/57 (0.00%)2/59 (3.39%)
# events05
Injury, poisoning and procedural complications  
Fall1, †  
# participants affected / at risk 1/57 (1.75%)2/59 (3.39%)
# events14
Injury, poisoning and procedural complications  
Post procedural complication1, †  
# participants affected / at risk 10/57 (17.54%)11/59 (18.64%)
# events1211
Injury, poisoning and procedural complications  
Post procedural fever1, †  
# participants affected / at risk 2/57 (3.51%)4/59 (6.78%)
# events24
Injury, poisoning and procedural complications  
Procedural pain1, †  
# participants affected / at risk 0/57 (0.00%)3/59 (5.08%)
# events03
Musculoskeletal and connective tissue disorders  
Arthralgia1, †  
# participants affected / at risk 3/57 (5.26%)3/59 (5.08%)
# events43
Musculoskeletal and connective tissue disorders  
Back pain1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Musculoskeletal and connective tissue disorders  
Bursitis1, †  
# participants affected / at risk 2/57 (3.51%)0/59 (0.00%)
# events20
Musculoskeletal and connective tissue disorders  
Musculoskeletal chest pain1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events31
Musculoskeletal and connective tissue disorders  
Myalgia1, †  
# participants affected / at risk 1/57 (1.75%)3/59 (5.08%)
# events13
Nervous system disorders  
Headache1, †  
# participants affected / at risk 8/57 (14.04%)6/59 (10.17%)
# events89
Respiratory, thoracic and mediastinal disorders  
Cough1, †  
# participants affected / at risk 4/57 (7.02%)6/59 (10.17%)
# events59
Respiratory, thoracic and mediastinal disorders  
Dysphonia1, †  
# participants affected / at risk 2/57 (3.51%)2/59 (3.39%)
# events22
Respiratory, thoracic and mediastinal disorders  
Nasal congestion1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Respiratory, thoracic and mediastinal disorders  
Oropharyngeal pain1, †  
# participants affected / at risk 2/57 (3.51%)6/59 (10.17%)
# events26
Vascular disorders  
Hypertension1, †  
# participants affected / at risk 2/57 (3.51%)1/59 (1.69%)
# events21
Events were collected by systematic assessment
1Term from vocabulary,  MedDRA 23.1

Primary Outcome Measures:

  • The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies. [ Time Frame: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic. ] [ Designated as safety issue:  ]
    The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.

Secondary Outcome Measures:

  • The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies [ Time Frame: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic. ] [ Designated as safety issue:  ]
    The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies

  • The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies [ Time Frame: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic. ] [ Designated as safety issue:  ]
    The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies

  • The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies [ Time Frame: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic. ] [ Designated as safety issue:  ]
    The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies

Other Pre-specified Outcome Measures:

  • [ Time Frame:  ] [ Designated as safety issue:  ]

ArmsAssigned Interventions
Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Biological/Vaccine: Tezepelumab
Tezepelumab subcutaneous injection
 
Placebo Comparator: Placebo
Placebo subcutaneous injection
Other: Placebo
Placebo subcutaneous injection
 

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description: 

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:Globall Clinical Head
Organization:AstraZeneca
Phone+1 877-240-9479 
E-mail:[email protected]