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AsthmaPhase 3NCT05280418

Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma

A Phase 3 study testing Tezepelumab in people with Asthma, run by McMaster University at 1 site in Canada.

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

In adult patients with uncontrolled moderate-to-severe asthma, blocking TSLP with tezepelumab will improve ventilation heterogeneity (evaluated by hyperpolarized 129Xe MRI), and this will be associated with reduced airway inflammation (evaluated by sputum composition), luminal narrowing and plugging (evaluated by CT). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Asthma
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
27 participants
Where
1 siteCanada
Study dates
8 Nov 2022to 17 Dec 2025
Phase
Phase 3
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General
  • Able and willing to provide written informed consent.
  • Able and willing to comply with the study protocol.
  • Males and females ≥ 18 years of age.
  • Asthma-related
  • Asthma diagnosed by a respiratory physician ≥12 months prior to study enrolment based on the Global Initiative for Asthma (GINA) 2021 guidelines.
Show all 11Show fewer
  • ACQ ≥1.5 at screening.
  • Methacholine PC20 ≤ 4 mg/mL OR ≥15% decrease in FEV1 during saline inhalation for sputum induction OR ≥15% improvement in FEV1 after bronchodilator during the screening period.
  • Criteria met for moderate or severe asthma defined by GINA 2021 guidelines, i.e. treatment with low, medium or high dose ICS (<250 mcg, 251 - 500 mcg, >500 mcg of fluticasone equivalent/day respectively) plus another controller. Patients on prednisone would not be excluded, as long as they meet the rest of the inclusion criteria.
  • FeNO >25 ppb OR ≥3% sputum eosinophils (preferred) OR blood eos ≥300/µL during the screening period.
  • History of ≥1 exacerbation in the previous year.

Who cannot join

  • General
  • -- Participation in any clinical trial of an investigational agent or procedure within six months prior to screening or during the study.
  • Medical conditions and treatment history
  • History of anaphylaxis to any previous biologic therapy received.
  • Receipt of live attenuated vaccine within 30 days, receipt of COVID vaccine within 28 days, known or suspected COVID infection at the time of enrollment.
  • Acute or chronic parasitic, bacterial, fungal or viral infections that required, or currently requires, hospitalization or antimicrobial treatment during the last four weeks.
Show all 16Show fewer
  • Acute asthma exacerbation event treated with increased doses of oral, or any dose of intramuscular (IM) or intravenous (IV) corticosteroids within six weeks prior to screening.
  • Other relevant pulmonary diseases (e.g. chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, tuberculosis) requiring treatment within 12 months prior to screening.
  • Alcohol or substance abuse within 12 months prior to screening.
  • Current smoker defined as having smoked at least one cigarette (or pipe, cigar, or marijuana) per day for ≥ 30 days within the three months prior to screening.
  • Ex-smokers with ≥ 10 pack-year smoking history.
  • Pregnancy.
  • Treatment with anti-IgE, anti-IL-4, anti-IL-5, or anti-IL-13 targeted therapy currently or within three months prior to screening.
  • MRI-related
  • Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist).
  • In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Firestone Institute for Respiratory Health

    Hamilton, Ontario, L8N 4A6

Other trials in Canada

About this study

Official title: A Two-arm, Placebo-controlled, Randomized Clinical Trial to Evaluate the Effect of Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma

In adult patients with uncontrolled moderate-to-severe asthma, blocking TSLP with tezepelumab will improve ventilation heterogeneity (evaluated by hyperpolarized 129Xe MRI), and this will be associated with reduced airway inflammation (evaluated by sputum composition), luminal narrowing and plugging (evaluated by CT).

Read the detailed description

The luminal obstruction in asthma that contributes to symptoms is due to inflammatory cells (usually eosinophils or neutrophils), mucus, smooth muscle constriction, airway wall thickness, or a combination of the above. This obstruction can be regionally visualized and quantified by computed tomography (CT), and its functional consequence can be assessed at high resolution using inhaled hyperpolarized 129Xe gas magnetic resonance imaging (MRI). Thymic stromal lymphopoietin (TSLP), an epithelial cell derived cytokine that is produced in response to environmental and proinflammatory stimuli, may contribute to all of these features of asthma through its downstream effects on a wide variety of immune (e.g. eosinophils, mast cells, group 2 innate lymphoid cells (ILC2s), Th2 cell, and Th17 cells) and structural cells (e.g. smooth muscle cells, and fibroblasts). Of note, TSLP is believed to upregulate multiple downstream inflammatory pathways, including IL-4, IL-5 and IL-13 signalling. It is also believed to mediate structural mechanisms that contribute to airway remodelling and smooth muscle dysfunction.

The consequence of blocking TSLP with tezepelumab on airway structure and function has not been investigated. This study will use CT to quantify airway wall and lumen structure according to previously described methods. CT images will also be evaluated for intraluminal plugging and a visual mucus score will be generated. Ventilation heterogeneity in asthmatics, the functional consequence of luminal obstruction, can be regionally measured with high temporal and spatial resolution using inhaled hyperpolarized gas MRI. In asthmatics, focal ventilation defects are observed and these have been shown to be spatially related to airway abnormalities and to respond to bronchoconstriction, bronchodilation, and anti-T2 biologics.

Due to the potential effect of tezepelumab on luminal inflammation, smooth muscle dysfunction and mucus hypersecretion, it is believed that MRI-detectable improvements in ventilation heterogeneity will be observed in asthmatics.

Conditions
Asthma
Being tested
Tezepelumab, Placebo
Medical subject headings
Asthma

What participants receive

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

  • TezepelumabBiological

    Monoclonal antibody designed for the treatment asthma.

  • PlaceboBiological

    Matched placebo.

Study groups in NCT05280418
Study groupRoleWhat they receive
TezepelumabActive comparatorTezepelumab 210 mg subcutaneous injections every 4 weeks as an investigational drug. Sterile tezepelumab will be provided 110 mg/mL pre-filled vial, with a dose of 210 mg delivered by pre-filled syringe.
Receives: Biological: Tezepelumab
Matched placeboPlacebo comparatorSterile placebo for tezepelumab will be provided in identically matched pre-filled syringes.
Receives: Biological: Placebo

What is being measured

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

  1. Change in pre-bronchodilator 129Xe MRI ventilation defect percent (VDP).

    Change from baseline to week 16 in the pre-bronchodilator 129Xe MRI ventilation defect percent (VDP).

    Measured: 16 weeks from randomization (week 0) to endpoint assessment (week 16)

Secondary outcomes (8)

  1. Change in the post-bronchodilator 129Xe MRI ventilation defect percent (VDP).

    Change in the post-bronchodilator 129Xe MRI ventilation defect percent (VDP) measured as percent of total ventilation.

    Measured: From baseline (week 0) to endpoint (week 16)

  2. Change in the CT mucus score (i.e. intraluminal plugging).

    Change in the CT mucus score (i.e. intraluminal plugging) measured using a mucus score.

    Measured: From baseline (week 0) to endpoint (week 16)

  3. Change in the CT airway lumen area.

    Change in the CT airway lumen area measured in mm^2.

    Measured: From baseline (week 0) to endpoint (week 16)

  4. Change in the CT airway wall area.

    Change in the CT airway wall area measured in mm^2.

    Measured: From baseline (week 0) to endpoint (week 16)

  5. Change in the CT airway wall area percentage.

    Change in the CT airway wall area percentage measured as a percentage of total airway area (wall area + airway lumen).

    Measured: From baseline (week 0) to endpoint (week 16)

  6. Change in the CT total airway count.

    Change in the CT total airway count

    Measured: From baseline (week 0) to endpoint (week 16)

  7. Change in the CT gas trapping.

    Change in the CT gas trapping

    Measured: From baseline (week 0) to endpoint (week 16)

  8. Change in the post-bronchodilator reversibility of 129Xe MRI VDP.

    Change in the post-bronchodilator reversibility of 129Xe MRI VDP measured by ventilation defect percentage of total ventilation

    Measured: From baseline (week 0) to endpoint (week 16)

Timeline

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

  1. First posted15 Mar 2022
  2. Study start8 Nov 2022
  3. Primary completion5 Nov 2025
  4. Study completion17 Dec 2025

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05280418
Sponsor's protocol ID
ESR-20-210000
Status last verified
Dec 2025
First submitted
11 Feb 2022
Last updated
7 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020 Aug;24(8):777-792. doi: 10.1080/14728222.2020.1783242. Epub 2020 Jun 27.

    PubMed 32567399

  • Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, Raymond WW, Lachowicz-Scroggins ME, Di Maio S, Hoffman EA, Castro M, Fain SB, Jarjour NN, Israel E, Levy BD, Erzurum SC, Wenzel SE, Meyers DA, Bleecker ER, Phillips BR, Mauger DT, Gordon ED, Woodruff PG, Peters MC, Fahy JV; National Heart Lung and Blood Institute (NHLBI) Severe Asthma Research Program (SARP). Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018 Mar 1;128(3):997-1009. doi: 10.1172/JCI95693. Epub 2018 Feb 5.

    PubMed 29400693

  • Svenningsen S, Haider E, Boylan C, Mukherjee M, Eddy RL, Capaldi DPI, Parraga G, Nair P. CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma. Chest. 2019 Jun;155(6):1178-1189. doi: 10.1016/j.chest.2019.02.403. Epub 2019 Mar 23.

    PubMed 30910637

  • Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, Brightling CE, Griffiths JM, Hellqvist A, Bowen K, Kaur P, Almqvist G, Ponnarambil S, Colice G. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021 May 13;384(19):1800-1809. doi: 10.1056/NEJMoa2034975.

    PubMed 33979488

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tezepelumab in people with Asthma, run by McMaster University at 1 site in Canada.

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

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. 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 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change in pre-bronchodilator 129Xe MRI ventilation defect percent (VDP). (time frame: 16 weeks from randomization (week 0) to endpoint assessment (week 16)). 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 NCT05280418, 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 7 Jan 2026.

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