Clinical trial NCT03688074: Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Keywords: Asthma
Uncontrolled asthma
Severe uncontrolled asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2018-09-28
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary purpose: TREATMENT

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. 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.

Eligibility 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.

Primary outcomes:
measure: Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT.
timeFrame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Secondary outcomes:
measure: Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT.
timeFrame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
measure: Percent (%) Airway Epithelial Integrity Ratio Change From Baseline to EOT.
timeFrame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
Other outcomes:
Locations:
city: Denver
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Galveston
country: United States
facility: Research Site
state: Texas
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Aarhus N
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Naestved
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Landsberg
country: Germany
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Headington
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Wythenshawe
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of Leicester, United Kingdom
name: Chris Brightling
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pham 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.
citation: Diver 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.
citation: Emson 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.