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

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ClinicalTrials.gov Identifier: NCT03688074
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : April 11, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE September 26, 2018
First Posted Date  ICMJE September 28, 2018
Last Update Posted Date April 11, 2019
Actual Study Start Date  ICMJE November 2, 2018
Estimated Primary Completion Date January 11, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies. [ Time Frame: Week 28 ]
The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03688074 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
  • The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies [ Time Frame: Week 28 ]
    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: Week 28 ]
    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: Week 28 ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description This is a multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of tezepelumab on airway inflammation in adults with inadequately controlled moderate-to-severe asthma, taking inhaled corticosteroids and at least one additional asthma controller. Approximately 110 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 28-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-blind
Primary Purpose: Treatment
Condition  ICMJE
  • Asthma
  • Bronchial Diseases
  • Respiratory Tract Diseases
  • Lung Diseases, Obstructive
  • Lung Diseases
  • Respiratory Hypersensitivity
  • Hypersensitivity, Immediate
  • Hypersensitivity
  • Immune System Diseases
Intervention  ICMJE
  • Biological: Tezepelumab
    Tezepelumab subcutaneous injection
  • Other: Placebo
    Placebo subcutaneous injection
Study Arms  ICMJE
  • Experimental: Tezepelumab
    Tezepelumab subcutaneous injection
    Intervention: Biological: Tezepelumab
  • Placebo Comparator: Placebo
    Placebo subcutaneous injection
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 26, 2018)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 11, 2021
Estimated Primary Completion Date January 11, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Principal 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. Former smokers with a smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit 1
  • 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 the current study or previous tezepelumab studies
  • Pregnant, breastfeeding or lactating women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Canada,   Denmark,   Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03688074
Other Study ID Numbers  ICMJE D5180C00013
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Chris Brightling University of Leicester, United Kingdom
PRS Account AstraZeneca
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP