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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 : November 27, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Biological: Tezepelumab Other: Placebo Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 110 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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blind
Primary Purpose: Treatment
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)
Actual Study Start Date : November 2, 2018
Estimated Primary Completion Date : January 11, 2021
Estimated Study Completion Date : January 11, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Biological: Tezepelumab
Tezepelumab subcutaneous injection

Placebo Comparator: Placebo
Placebo subcutaneous injection
Other: Placebo
Placebo subcutaneous injection




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03688074


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 28 Study Locations
Sponsors and Collaborators
AstraZeneca
Amgen
Investigators
Principal Investigator: Chris Brightling University of Leicester, United Kingdom

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03688074     History of Changes
Other Study ID Numbers: D5180C00013
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018

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

Keywords provided by AstraZeneca:
Asthma
Uncontrolled asthma
Severe uncontrolled asthma

Additional relevant MeSH terms:
Asthma
Inflammation
Lung Diseases
Hypersensitivity
Respiratory Tract Diseases
Immune System Diseases
Lung Diseases, Obstructive
Bronchial Diseases
Hypersensitivity, Immediate
Respiratory Hypersensitivity
Pathologic Processes