Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma

A Phase 2 Multi-centre Randomized Double-blind Placebo-controlled Parallel Group Study to Examine the Effects of 24 Weeks Tezepelumab 210 mg sc q4wks on Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma

Asthma is a condition where small inhaled particles can cause inflammation in the lung leading to constriction of airways and wheeze. Mast cells are immune cells in airways that can release chemical causing constriction of the airways and wheeze. Tezepelumab is an injectable medication that improves asthma by stopping inflammation, but the effect on mast cells is not known. Tezepelumab was approved in Canada July 2022 for treatment of severe asthma. Tezepelumab is not approved for treatment of mild asthma by any health authority, except for use in research studies like this. This study will examine the effect of tezepelumab on mast cells and airway constriction to understand the mechanisms of asthma, and which patients will benefit most from drugs like tezepelumab.

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma, Allergic
• Intervention / Treatment: Drug: Tezepelumab; Drug: Placebo

Detailed Description

The proposed study will address whether tezepelumab has the unique ability to improve AHR in participants with mild allergic asthma.

This is a phase 2 multi-centre randomized double-blind placebo-controlled parallel-group study to examine the effects of 24 weeks tezepelumab 210 mg sc q4wks on methacholine airway hyperresponsiveness in participants with mild allergic asthma, stratified for sex and sensitivity to seasonal allergens.

There are 9 study visits over a period of 27 weeks (Figure 1). Study procedures performed at Weeks -1, 8, 16 and 24 will be divided across 2 visits at least 48 hours apart for measurement of AHR to methacholine first, and mannitol at least 48 hours later.

The screening period at Week -1 will determine eligibility. At Week -1, eligible allergic mild asthmatic participants will be randomized 1:1 to placebo or tezepelumab 210 mg subcutaneous administered monthly for a total of 24 weeks. AHR will be measured by methacholine and mannitol challenges at baseline (Week -1) performed at least 48 hours apart. Changes in AHR response will be measured by repeat methacholine and mannitol challenges at Weeks 8, 16 and 24.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gail M Gauvreau, PhD; Phone Number: 22791 9055259140; Email: gauvreau@mcmaster.ca
• Study Contact Backup: Name: Paul M O'Byrne, MB; Phone Number: 22100 9055259140; Email: obyrnep@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
      • Contact: Gail M Gauvreau, PhD; Phone Number: 22791 9055259140; Email: gauvreau@mcmaster.ca
      • Contact: Paul M O'Byrne, MB; Phone Number: 22100 9055259140; Email: obyrne@mcmaster.ca
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • University of Saskatchewan
      • Contact: Beth Davis, PhD; Phone Number: (306) 844-1444; Email: beth.davis@usask.ca
      • Contact: Donald Cockcroft, MD; Phone Number: (306) 844-1444; Email: don.cockcroft@usask.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Male and female 18 through 65 years of age
3. Positive skin-prick test to a common aeroallergen
4. Methacholine PD20 ≤ 200mcg
5. Mannitol DRR ≤ 42.3mg/FEV1 %f all (equivalent to PD15 ≤ 635mg)
6. Baseline FEV1 ≥ 70% of the predicted value
7. Negative pregnancy test (urine) for female participants of childbearing potential.

Exclusion Criteria:

1. Current or former smoker with >10-pack-year history
2. Current or previous history of lung disease other than mild stable allergic asthma
3. Significant systemic disease, including history of current malignancy or autoimmune disease
4. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
5. Previous randomisation in the present study. Re-screening (Week -1) for FEV1 and AHR is permitted once for each test.
6. Participation in another clinical study with an investigational product during the last 30 days or 5 half-lives of the drug (whichever is longer)
7. Use of any medications for treatment of asthma other than prophylactic short-acting β2-agonists, or use of short-acting β2-agonists for relief of symptoms less than once weekly.
8. Participants with known hypersensitivity to tezepelumab or any of the excipients of the product.
9. Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening
10. Known to have tested positive for human immunodeficiency virus
11. Known history of drug or alcohol abuse within 1 year of screening
12. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding.
13. Unwillingness or inability to comply with the study protocol for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tezepelumab; tezepelumab 210 mg sc q4wks 20 weeks treatment	Drug: Tezepelumab; tezepelumab 210 mg sc q4wks for 20 weeks
Placebo Comparator: Placebo; placebo sc q4wks 20 weeks treatment	Drug: Placebo; placebo sc q4wks for 20 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methacholine PD20	The provocative dose of methacholine causing 20% fall in FEV1	Week -1 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose response ratio to mannitol	The mannitol dose response ratio calculated by dividing the total cumulative dose by the % fall in FEV1 at that dose.	Week -1 to Week 24
Mast cell tryptase levels.	Level of mast cell-derived tryptase in blood and urine at Week 24.	Week -1 to Week 24

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: asthma; tezepelumab; mast cell; airway hyperresponsiveness; Thymic stromal lymphopoietin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Hypersensitivity; Asthma; Respiratory Hypersensitivity
• Other Study ID Numbers: ESR-22-21828

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No