AsthmaPhase 2CASCADENCT03688074

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

A Phase 2 study testing Tezepelumab in people with Asthma and Bronchial Diseases, run by AstraZeneca at 28 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Asthma, Bronchial Diseases, Respiratory Tract Diseases
What is being tested?: Tezepelumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 116 participants
Where: 28 sitesin 5 countries
Study dates: 2 Nov 2018to 16 Nov 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

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.

Trial locations and contacts

28 sites in 5 countries.

Country

City, postcode or hospital

28 sites in 5 countries

Denmark7 sites

Research Site
Aalborg, 9000
Research Site
Aarhus N, 8200
Research Site
Hvidovre, 2650
Research Site
København NV, 2400
Research Site
Næstved, 4700
Research Site
Odense C, 5000
Research Site
Vejle, 7100

Other trials in Denmark

Canada6 sites

Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Hamilton, Ontario, L8N 3Z5
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Québec, Quebec, G1V 4G5
Research Site
Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

United Kingdom6 sites

Research Site
Cambridge, CB2 0QQ
Research Site
Headington, OX3 9DU
Research Site
Leicester, LE3 9QP
Research Site
London, W1G 8HU
Research Site
Nottingham, NG5 1PB
Research Site
Wythenshawe, M23 9QZ

Other trials in United Kingdom

United States5 sites

Research Site
Boston, Massachusetts, 02115
Research Site
Denver, Colorado, 80206
Research Site
Galveston, Texas, 77555
Research Site
New Haven, Connecticut, 06510
Research Site
Pittsburgh, Pennsylvania, 15213

Other trials in United States

Germany4 sites

Research Site
Frankfurt, 60596
Research Site
Frankfurt am Main, 60389
Research Site
Großhansdorf, 22927
Research Site
Landsberg, 86899

Other trials in Germany

About this study

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)

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.

Read the 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.

Conditions: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity
Being tested: Tezepelumab, Placebo
Keywords: Asthma, Uncontrolled asthma, Severe uncontrolled asthma
Medical subject headings: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Hypersensitivity, Immediate, Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TezepelumabBiological
Tezepelumab subcutaneous injection
PlaceboOther
Placebo subcutaneous injection

Study groups in NCT03688074
Study group	Role	What they receive
Tezepelumab	Experimental	Tezepelumab subcutaneous injection Receives: Biological: Tezepelumab
Placebo	Placebo comparator	Placebo subcutaneous injection Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in RBM thickness, determined by microscopic evaluation of bronchoscopic biopsies.
Measured: 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.
The change from baseline to EOT expressed as a ratio i.e. (EOT/baseline) in % airway epithelial, determined by microscopic evaluation of bronchoscopic biopsies.
Measured: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Nov 201816 Nov 2020

First posted28 Sep 2018
Study start2 Nov 2018
Primary completion16 Nov 2020
Study completion16 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 116 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03688074
Sponsor's protocol ID: D5180C00013
Acronym: CASCADE
Status last verified: Feb 2022
First submitted: 26 Sep 2018
Last updated: 21 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 38320181
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.
PubMed 34403803
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.
PubMed 34256031
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.
PubMed 33050900

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03688074
Acronym / sponsor ID: CASCADE / D5180C00013
Conditions: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity
Keywords: Asthma, Uncontrolled asthma, Severe uncontrolled asthma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 116 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Amgen
Study start: 2 Nov 2018 (actual)
Primary completion: 16 Nov 2020 (actual)
Study completion: 16 Nov 2020 (actual)
First posted: 28 Sep 2018 (actual)
Results: Posted 21 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.

Arm	Type	Receives
Tezepelumab	Experimental	Biological: TezepelumabTezepelumab subcutaneous injection
Placebo	Placebo comparator	Other: PlaceboPlacebo subcutaneous injection

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TezepelumabTezepelumab subcutaneous injection	Biological	Tezepelumab
PlaceboPlacebo subcutaneous injection	Other	Placebo

Primary outcome

Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT.
Time frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).
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.

2 secondary outcomes

Reticular Basement Membrane (RBM) Thickness Ratio Change From Baseline to EOT.
Time frame: 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.
Time frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).

Results and safety

Results posted to the registry on 21 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Teze 210 mg Q4W	59	58
Placebo	57	56

Primary outcome: Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT.

Time frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).. Geometric least squares mean (90% Confidence Interval). Unit: Ratio

Measure	Teze 210 mg Q4W n = 54	Placebo n = 56
Eosinophils	0.11 (0.06 to 0.21)	0.75 (0.41 to 1.38)
Neutrophils	1.11 (0.88 to 1.39)	0.81 (0.66 to 1.01)
T cells CD3+	0.91 (0.78 to 1.07)	0.81 (0.70 to 0.95)
T cells CD4+	0.96 (0.82 to 1.14)	0.81 (0.70 to 0.95)
Mast cells Tryptase+	0.84 (0.70 to 1.02)	1.01 (0.84 to 1.22)
Mast cells Chymase+	1.07 (0.76 to 1.52)	0.90 (0.65 to 1.26)

Teze 210 mg Q4W vs Placebo: Ratio of Geometric LSMeans: 0.15 (90% CI 0.06 to 0.35), p <0.001, ANCOVA
Teze 210 mg Q4W vs Placebo: Ratio of Geometric LSMeans: 1.36 (90% CI 0.99 to 1.86), p = 0.106, ANCOVA
Teze 210 mg Q4W vs Placebo: Ratio of Geometric LSMeans: 1.12 (90% CI 0.90 to 1.40), p = 0.389, ANCOVA

Population analysed: Number of Participants Analyzed are all subjects randomized to study treatment who completed at least 20 weeks of study treatment and had an EOT visit not greater than 8 weeks after date of last dose of IP. In order to be included in analysis, the participants also had to have a non-missing baseline as well as a non-missing EOT assessment for the respective variable.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	7 of 57 (12.3%)	45 of 57 (78.9%)	0 of 57
Teze 210 mg Q4W	3 of 59 (5.1%)	48 of 59 (81.4%)	0 of 59

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38320181Nordenmark 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.
Derived from this study: PubMed 34403803Pham 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.
Derived from this study: PubMed 34256031Diver 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.
Derived from this study: PubMed 33050900Emson 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.
Statistical Analysis Plan (SAP)Link provided by the sponsor.
CSPLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Chris Brightling principal investigator

University of Leicester, United Kingdom

28 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tezepelumab in people with Asthma and Bronchial Diseases, run by AstraZeneca at 28 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Denmark, Canada, United Kingdom, United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Airway Submucosal Inflammatory Cells Ratio Change From Baseline to EOT. (time frame: First dose of investigational product to end of treatment (EOT) at Week 28 (or up to Week 48 due to COVID19 pandemic).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03688074, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2022.