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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 : Active, not recruiting
First Posted : September 28, 2018
Last Update Posted : August 12, 2020
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. Although, due to the Covid-19 pandemic this may be an extended time frame for some subject visits. The study also includes a post-treatment follow-up period of 12 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 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 : November 16, 2020
Estimated Study Completion Date : November 16, 2020

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: 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. ]
    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: 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. ]
    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: 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. ]
    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: 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. ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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, 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.

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


Locations
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United States, Colorado
Research Site
Denver, Colorado, United States, 80206
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Research Site
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Research Site
Galveston, Texas, United States, 77555
Canada, Alberta
Research Site
Calgary, Alberta, Canada, T2N 4Z6
Canada, British Columbia
Research Site
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Research Site
Hamilton, Ontario, Canada, L8N 3Z5
Research Site
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H4A 3J1
Canada
Research Site
Quebec, Canada, G1V 4G5
Denmark
Research Site
Aarhus N, Denmark, 8200
Research Site
Hvidovre, Denmark, 2650
Research Site
København NV, Denmark, 2400
Research Site
Naestved, Denmark, 4700
Research Site
Odense C, Denmark, 5000
Research Site
Vejle, Denmark, 7100
Research Site
Ålborg, Denmark, 9000
Germany
Research Site
Frankfurt/Main, Germany, 60389
Research Site
Frankfurt, Germany, 60596
Research Site
Grosshansdorf, Germany, 22927
Research Site
Landsberg, Germany, 86899
United Kingdom
Research Site
Cambridge, United Kingdom, CB2 0QQ
Research Site
Leicester, United Kingdom, LE3 9QP
Research Site
London, United Kingdom, W1G 8HU
Research Site
Manchester, United Kingdom, M23 9QZ
Research Site
Nottingham, United Kingdom, NG5 1PB
Research Site
Oxford, United Kingdom, OX3 7FZ
Sponsors and Collaborators
AstraZeneca
Amgen
Investigators
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Principal Investigator: Chris Brightling University of Leicester, United Kingdom
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03688074    
Other Study ID Numbers: D5180C00013
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: August 12, 2020
Last Verified: August 2020

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