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

NCT05280418 | Completed Phase 3

• 1 other identifier: ESR-20-210000
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Asthma

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (8)

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

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

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

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

• Change in the CT airway lumen area.

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

• Change in the CT airway wall area.

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

• Change in the CT airway wall area percentage.

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

Other Outcomes (15)

• Change in ACQ-5 score.

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

• Change in AQLQ score.

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

• Change in the pre-bronchodilator and post-bronchodilator FEV1.

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

Study Arms (2)

Tezepelumab

ACTIVE COMPARATOR

Tezepelumab 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.

Biological: Tezepelumab

Matched placebo

PLACEBO COMPARATOR

Sterile placebo for tezepelumab will be provided in identically matched pre-filled syringes.

Biological: Placebo

Interventions

Tezepelumab BIOLOGICAL

Monoclonal antibody designed for the treatment asthma.

Tezepelumab

Placebo BIOLOGICAL

Matched placebo.

Matched placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

Firestone Institute for Respiratory Health

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (4)

• 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.

  PMID: 32567399 BACKGROUND

• 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.

  PMID: 29400693 BACKGROUND

• 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.

  PMID: 30910637 BACKGROUND

• 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.

  PMID: 33979488 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: March 15, 2022
• Study Start: November 8, 2022
• Primary Completion: November 5, 2025
• Study Completion: December 17, 2025
• Last Updated: January 7, 2026

Record last verified: 2025-12

Locations

CA (1)