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

NCT ID: NCT03688074

Last Updated: 2022-02-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-02

Study Completion Date

2020-11-16

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double-blind

Study Groups

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Tezepelumab

Tezepelumab subcutaneous injection

Group Type EXPERIMENTAL

Tezepelumab

Intervention Type BIOLOGICAL

Tezepelumab subcutaneous injection

Placebo

Placebo subcutaneous injection

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo subcutaneous injection

Interventions

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Tezepelumab

Tezepelumab subcutaneous injection

Intervention Type BIOLOGICAL

Placebo

Placebo subcutaneous injection

Intervention Type OTHER

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chris Brightling

Role: PRINCIPAL_INVESTIGATOR

University of Leicester, United Kingdom

Locations

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Research Site

Denver, Colorado, United States

Site Status

Research Site

New Haven, Connecticut, United States

Site Status

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Boston, Massachusetts, United States

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Pittsburgh, Pennsylvania, United States

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Galveston, Texas, United States

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Aalborg, , Denmark

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Aarhus N, , Denmark

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Hvidovre, , Denmark

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København NV, , Denmark

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Næstved, , Denmark

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Odense C, , Denmark

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Vejle, , Denmark

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Frankfurt, , Germany

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Frankfurt am Main, , Germany

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Großhansdorf, , Germany

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Landsberg, , Germany

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Cambridge, , United Kingdom

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Headington, , United Kingdom

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Leicester, , United Kingdom

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London, , United Kingdom

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Nottingham, , United Kingdom

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Research Site

Wythenshawe, , United Kingdom

Site Status

Countries

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United States Canada Denmark Germany United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38320181 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34403803 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34256031 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33050900 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D5180C00013

Identifier Type: -

Identifier Source: org_study_id

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