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

Asthma Clinical Trial

— CASCADE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03688074
• Other study ID #: D5180C00013
• Status: Completed
• Phase: Phase 2
• Start date: November 2, 2018
• Est. completion date: November 16, 2020

Study information

• Verified date: February 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: November 16, 2020
• Est. primary completion date: November 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Bronchial Diseases
• Hypersensitivity
• Hypersensitivity, Immediate
• Immune System Diseases
• Inflammation
• Lung Diseases
• Lung Diseases, Obstructive
• Respiratory Hypersensitivity
• Respiratory Tract Diseases

Intervention

Biological:
• Tezepelumab
Tezepelumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	Aarhus N
Denmark	Research Site	Ålborg
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Naestved
Denmark	Research Site	Odense C
Denmark	Research Site	Vejle
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Grosshansdorf
Germany	Research Site	Landsberg
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Headington
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Wythenshawe
United States	Research Site	Boston	Massachusetts
United States	Research Site	Denver	Colorado
United States	Research Site	Galveston	Texas
United States	Research Site	New Haven	Connecticut
United States	Research Site	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT.	The 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.	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Secondary	Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT.	The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Secondary	Percent (%) Airway Epithelial Integrity Ratio Change From Baseline to EOT.	The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.	First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

External Links

•   CSP
•   Statistical Analysis Plan (SAP)