Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)
CASCADE
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)
1 other identifier
interventional
116
5 countries
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 asthma
Started Nov 2018
Typical duration for phase_2 asthma
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2018
CompletedFirst Posted
Study publicly available on registry
September 28, 2018
CompletedStudy Start
First participant enrolled
November 2, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 16, 2020
CompletedResults Posted
Study results publicly available
February 21, 2022
CompletedFebruary 21, 2022
February 1, 2022
2 years
September 26, 2018
November 12, 2021
February 18, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT.
First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Percent (%) Airway Epithelial Integrity Ratio Change From Baseline to EOT.
First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Study Arms (2)
Tezepelumab
EXPERIMENTALTezepelumab subcutaneous injection
Placebo
PLACEBO COMPARATORPlacebo subcutaneous injection
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Amgencollaborator
Study Sites (28)
Research Site
Denver, Colorado, 80206, United States
Research Site
New Haven, Connecticut, 06510, United States
Research Site
Boston, Massachusetts, 02115, United States
Research Site
Pittsburgh, Pennsylvania, 15213, United States
Research Site
Galveston, Texas, 77555, United States
Research Site
Calgary, Alberta, T2N 4Z6, Canada
Research Site
Vancouver, British Columbia, V5Z 1M9, Canada
Research Site
Hamilton, Ontario, L8N 3Z5, Canada
Research Site
Ottawa, Ontario, K1H 8L6, Canada
Research Site
Montreal, Quebec, H4A 3J1, Canada
Research Site
Québec, Quebec, G1V 4G5, Canada
Research Site
Aalborg, 9000, Denmark
Research Site
Aarhus N, 8200, Denmark
Research Site
Hvidovre, 2650, Denmark
Research Site
København NV, 2400, Denmark
Research Site
Næstved, 4700, Denmark
Research Site
Odense C, 5000, Denmark
Research Site
Vejle, 7100, Denmark
Research Site
Frankfurt, 60596, Germany
Research Site
Frankfurt am Main, 60389, Germany
Research Site
Großhansdorf, 22927, Germany
Research Site
Landsberg, 86899, Germany
Research Site
Cambridge, CB2 0QQ, United Kingdom
Research Site
Headington, OX3 9DU, United Kingdom
Research Site
Leicester, LE3 9QP, United Kingdom
Research Site
London, W1G 8HU, United Kingdom
Research Site
Nottingham, NG5 1PB, United Kingdom
Research Site
Wythenshawe, M23 9QZ, United Kingdom
Related Publications (4)
Nordenmark LH, Hellqvist A, Emson C, Diver S, Porsbjerg C, Griffiths JM, Newell JD, Peterson S, Pawlikowska B, Parnes JR, Megally A, Colice G, Brightling CE. Tezepelumab and Mucus Plugs in Patients with Moderate-to-Severe Asthma. NEJM Evid. 2023 Oct;2(10):EVIDoa2300135. doi: 10.1056/EVIDoa2300135. Epub 2023 Sep 20.
PMID: 38320181DERIVEDPham TH, Chen C, Colice G, Parnes JR, Griffiths JM, Cook B. Tezepelumab normalizes serum interleukin-5 and -13 levels in patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2021 Dec;127(6):689-691. doi: 10.1016/j.anai.2021.08.008. Epub 2021 Aug 14. No abstract available.
PMID: 34403803DERIVEDDiver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, Johnston J, Molfino N, Parnes JR, Megally A, Colice G, Brightling CE; CASCADE study investigators. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021 Nov;9(11):1299-1312. doi: 10.1016/S2213-2600(21)00226-5. Epub 2021 Jul 10.
PMID: 34256031DERIVEDEmson C, Diver S, Chachi L, Megally A, Small C, Downie J, Parnes JR, Bowen K, Colice G, Brightling CE. CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma. Respir Res. 2020 Oct 13;21(1):265. doi: 10.1186/s12931-020-01513-x.
PMID: 33050900DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Results Point of Contact
- Title
- Globall Clinical Head
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Chris Brightling
University of Leicester, United Kingdom
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2018
First Posted
September 28, 2018
Study Start
November 2, 2018
Primary Completion
November 16, 2020
Study Completion
November 16, 2020
Last Updated
February 21, 2022
Results First Posted
February 21, 2022
Record last verified: 2022-02