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Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma

Primary Purpose

Asthma, Allergic

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Tezepelumab
Placebo
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma, Allergic focused on measuring asthma, airway hyperresponsiveness, mast cell, Thymic stromal lymphopoietin, tezepelumab

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of informed consent prior to any study specific procedures Male and female 18 through 65 years of age Positive skin-prick test to a common aeroallergen Methacholine PD20 ≤ 200mcg Mannitol DRR ≤ 42.3mg/FEV1 %f all (equivalent to PD15 ≤ 635mg) Baseline FEV1 ≥ 70% of the predicted value Negative pregnancy test (urine) for female participants of childbearing potential. Exclusion Criteria: Current or former smoker with >10-pack-year history Current or previous history of lung disease other than mild stable allergic asthma Significant systemic disease, including history of current malignancy or autoimmune disease Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) Previous randomisation in the present study. Re-screening (Week -1) for FEV1 and AHR is permitted once for each test. Participation in another clinical study with an investigational product during the last 30 days or 5 half-lives of the drug (whichever is longer) 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. Participants with known hypersensitivity to tezepelumab or any of the excipients of the product. Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening Known to have tested positive for human immunodeficiency virus Known history of drug or alcohol abuse within 1 year of screening For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding. Unwillingness or inability to comply with the study protocol for any other reason.

Sites / Locations

  • McMaster University
  • University of Saskatchewan

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tezepelumab

Placebo

Arm Description

tezepelumab 210 mg sc q4wks 20 weeks treatment

placebo sc q4wks 20 weeks treatment

Outcomes

Primary Outcome Measures

Methacholine PD20
The provocative dose of methacholine causing 20% fall in FEV1

Secondary Outcome Measures

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.
Mast cell tryptase levels.
Level of mast cell-derived tryptase in blood and urine at Week 24.

Full Information

First Posted
February 6, 2023
Last Updated
February 22, 2023
Sponsor
McMaster University
Collaborators
University of Saskatchewan
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1. Study Identification

Unique Protocol Identification Number
NCT05740748
Brief Title
Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
Collaborators
University of Saskatchewan

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Allergic
Keywords
asthma, airway hyperresponsiveness, mast cell, Thymic stromal lymphopoietin, tezepelumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tezepelumab
Arm Type
Experimental
Arm Description
tezepelumab 210 mg sc q4wks 20 weeks treatment
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo sc q4wks 20 weeks treatment
Intervention Type
Drug
Intervention Name(s)
Tezepelumab
Intervention Description
tezepelumab 210 mg sc q4wks for 20 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo sc q4wks for 20 weeks
Primary Outcome Measure Information:
Title
Methacholine PD20
Description
The provocative dose of methacholine causing 20% fall in FEV1
Time Frame
Week -1 to Week 24
Secondary Outcome Measure Information:
Title
Dose response ratio to mannitol
Description
The mannitol dose response ratio calculated by dividing the total cumulative dose by the % fall in FEV1 at that dose.
Time Frame
Week -1 to Week 24
Title
Mast cell tryptase levels.
Description
Level of mast cell-derived tryptase in blood and urine at Week 24.
Time Frame
Week -1 to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of informed consent prior to any study specific procedures Male and female 18 through 65 years of age Positive skin-prick test to a common aeroallergen Methacholine PD20 ≤ 200mcg Mannitol DRR ≤ 42.3mg/FEV1 %f all (equivalent to PD15 ≤ 635mg) Baseline FEV1 ≥ 70% of the predicted value Negative pregnancy test (urine) for female participants of childbearing potential. Exclusion Criteria: Current or former smoker with >10-pack-year history Current or previous history of lung disease other than mild stable allergic asthma Significant systemic disease, including history of current malignancy or autoimmune disease Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) Previous randomisation in the present study. Re-screening (Week -1) for FEV1 and AHR is permitted once for each test. Participation in another clinical study with an investigational product during the last 30 days or 5 half-lives of the drug (whichever is longer) 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. Participants with known hypersensitivity to tezepelumab or any of the excipients of the product. Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening Known to have tested positive for human immunodeficiency virus Known history of drug or alcohol abuse within 1 year of screening For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding. Unwillingness or inability to comply with the study protocol for any other reason.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gail M Gauvreau, PhD
Phone
9055259140
Ext
22791
Email
gauvreau@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Paul M O'Byrne, MB
Phone
9055259140
Ext
22100
Email
obyrnep@mcmaster.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gail Gauvreau, PhD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gail M Gauvreau, PhD
Phone
9055259140
Ext
22791
Email
gauvreau@mcmaster.ca
First Name & Middle Initial & Last Name & Degree
Paul M O'Byrne, MB
Phone
9055259140
Ext
22100
Email
obyrne@mcmaster.ca
Facility Name
University of Saskatchewan
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beth Davis, PhD
Phone
(306) 844-1444
Email
beth.davis@usask.ca
First Name & Middle Initial & Last Name & Degree
Donald Cockcroft, MD
Phone
(306) 844-1444
Email
don.cockcroft@usask.ca

12. IPD Sharing Statement

Plan to Share IPD
No

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Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma

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