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

Recruitment Status:
Active, not recruiting

Sponsor:
AstraZeneca

Collaborator:
Amgen

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT03688074

Verification:
Verified 01 May 2020   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:Active, not recruiting
Study Start Date:02 November 2018
Study Start Date Type:Actual
Primary Completion Date:16 September 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    information.center@astrazeneca.com  

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 1M9Active, not recruiting
United States of America , TXResearch Site Galveston, TX, United States of America, 77555Active, not recruiting
United States of America , MAResearch Site Boston, MA, United States of America, 02115Active, not recruiting
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Active, not recruiting
GermanyResearch Site Frankfurt, Germany, 60596Completed
GermanyResearch Site Frankfurt/Main, Germany, 60389Active, not recruiting
GermanyResearch Site Grosshansdorf, Germany, 22927Active, not recruiting
GermanyResearch Site Landsberg, Germany, 86899Active, not recruiting
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQActive, not recruiting
United KingdomResearch Site Headington, United Kingdom, OX3 9DUActive, not recruiting
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPActive, not recruiting
United KingdomResearch Site London, United Kingdom, W1G 8HUActive, not recruiting
United KingdomResearch Site Manchester, United Kingdom, M23 9QZActive, not recruiting
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBActive, not recruiting
United States of America , COResearch Site Denver, CO, United States of America, 80206Active, not recruiting
United States of America , FLResearch Site Clearwater, FL, United States of America, 33765Withdrawn
United States of America , CTResearch Site New Haven, CT, United States of America, 06520Withdrawn
United States of America , CAResearch Site Newport Beach, CA, United States of America, 92663Withdrawn
Canada , QCResearch Site Montreal, QC, Canada, H4A 3J1Active, not recruiting
Canada , QCResearch Site Quebec, QC, Canada, G1V 4G5Active, not recruiting
DenmarkResearch Site Aarhus N, Denmark, 8200Active, not recruiting
DenmarkResearch Site Ålborg, Denmark, 9000Active, not recruiting
DenmarkResearch Site Hvidovre, Denmark, 2650Active, not recruiting
DenmarkResearch Site København NV, Denmark, 2400Active, not recruiting
DenmarkResearch Site Naestved, Denmark, 4700Active, not recruiting
DenmarkResearch Site Odense C, Denmark, 5000Active, not recruiting
DenmarkResearch Site Vejle, Denmark, 7100Active, not recruiting
Canada , ONResearch Site Hamilton, ON, Canada, L8N 3Z5Active, not recruiting
Canada , ONResearch Site Ottawa, ON, Canada, K1H 8L6Completed

No attachments posted.

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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:Active, not recruiting
Study Start Date:02 November 2018
Study Start Date Type:Actual
Primary Completion Date:16 September 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    information.center@astrazeneca.com  

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 1M9Active, not recruiting
United States of America , TXResearch Site Galveston, TX, United States of America, 77555Active, not recruiting
United States of America , MAResearch Site Boston, MA, United States of America, 02115Active, not recruiting
United States of America , PAResearch Site Pittsburgh, PA, United States of America, 15213Active, not recruiting
GermanyResearch Site Frankfurt, Germany, 60596Completed
GermanyResearch Site Frankfurt/Main, Germany, 60389Active, not recruiting
GermanyResearch Site Grosshansdorf, Germany, 22927Active, not recruiting
GermanyResearch Site Landsberg, Germany, 86899Active, not recruiting
United KingdomResearch Site Cambridge, United Kingdom, CB2 0QQActive, not recruiting
United KingdomResearch Site Headington, United Kingdom, OX3 9DUActive, not recruiting
United KingdomResearch Site Leicester, United Kingdom, LE3 9QPActive, not recruiting
United KingdomResearch Site London, United Kingdom, W1G 8HUActive, not recruiting
United KingdomResearch Site Manchester, United Kingdom, M23 9QZActive, not recruiting
United KingdomResearch Site Nottingham, United Kingdom, NG5 1PBActive, not recruiting
United States of America , COResearch Site Denver, CO, United States of America, 80206Active, not recruiting
United States of America , FLResearch Site Clearwater, FL, United States of America, 33765Withdrawn
United States of America , CTResearch Site New Haven, CT, United States of America, 06520Withdrawn
United States of America , CAResearch Site Newport Beach, CA, United States of America, 92663Withdrawn
Canada , QCResearch Site Montreal, QC, Canada, H4A 3J1Active, not recruiting
Canada , QCResearch Site Quebec, QC, Canada, G1V 4G5Active, not recruiting
DenmarkResearch Site Aarhus N, Denmark, 8200Active, not recruiting
DenmarkResearch Site Ålborg, Denmark, 9000Active, not recruiting
DenmarkResearch Site Hvidovre, Denmark, 2650Active, not recruiting
DenmarkResearch Site København NV, Denmark, 2400Active, not recruiting
DenmarkResearch Site Naestved, Denmark, 4700Active, not recruiting
DenmarkResearch Site Odense C, Denmark, 5000Active, not recruiting
DenmarkResearch Site Vejle, Denmark, 7100Active, not recruiting
Canada , ONResearch Site Hamilton, ON, Canada, L8N 3Z5Active, not recruiting
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


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

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