Clinical trial NCT06705764: Tezepelumab in the Treatment of Emergency Room Asthma in Adults (TERAA)
Official title: Tezepelumab in the Treatment of Emergency Room Asthma in Adults (TERAA): A Phase 4 Double-Blinded, Parallel-Group, Randomized Control Trial With an Open Label Extension
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Severe Asthma
Keywords: Asthma
Severe Asthma
Asthma Exacerbation
Tezepelumab
Emergency deparment visits for asthma
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2024-11-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Adults with severe asthma may have sudden worsening shortness of breath that results in their going to Emergency Department for urgent care. Emergency Room visits for asthma management across Alberta have been reviewed and it has been found that adults frequently need to return for repeated worsening. This is a large drain on health care resources as well as being very distressing for individuals with asthma. Occasionally this results in admission to hospital and rarely may lead to death. People are often treated with steroids to try to prevent the need for Emergency Room visits even though steroid medications have many long term bad side effects.

A new medication for patients considered to have severe asthma has been recently approved by Health Canada. This medication, Tezepelumab, is a monthly injection and it helps control asthma in adults regardless of the underlying cause. The study will examine if starting Tezepelumab, compared with a placebo, in the Emergency Room will help settle symptoms of asthma and prevent future worsening requiring repeated Emergency Room visits or the need for courses of outpatient steroid medications.

Detailed description: All patients with a physician-diagnosed history of asthma and a history of a moderate or severe exacerbation of asthma presenting to the Emergency Department (ED) with an acute exacerbation of asthma will be reviewed by a study coordinator. From this population, subjects with at least 3-month history of prescription for a high dose inhaled corticosteroid (ICS) plus a reliever medication such as a long-acting beta2 agonist (LABA), long-acting muscarinic antagonist (LAMA) or a leukotriene receptor antagonist (LRTA) will be approached for study enrolment while still within the ED. Following informed consent, subject will be randomized in a 1:1 ratio to either Tezepelumab 210 mg S/Q Q4W or to a marching placebo. The proportion of subjects returning to ED for an exacerbation of asthma by Day-90 will serve as the primary study outcome. After Day-90 subjects will be entered into an open-label study with all receiving Tezepelumab 210 mg S/Q Q4W. A key secondary outcome will be the proportion of subjects returning to ED for an exacerbation of asthma by Day-180. Other secondary outcomes will include Alarmin expression, ACQ-5, FEV1 as well as study drug safety and tolerability

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male aged 18 to 55 years
3. History of physician-diagnosed asthma
4. All subjects will have been prescribed high dose inhaled corticosteroid (\> 500 ug fluticasone propionate dry powder formulation equivalents total daily dose. See Appendix C) plus at least one second controller (LABA, LAMA or LTRA) for at least 3 months prior to enrolment.
5. Documented history of at least one moderate or severe asthma exacerbation in the past 12 months
6. Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
7. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of study drug/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
8. Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of study drug.
9. Subject willing and able to comply with study procedures

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Participation in another clinical study with an investigational product during the last 6 months
4. Patients with a known hypersensitivity to Tezepelumab or any of the excipients of the product.
5. Patients who are admitted to hospital at screening.
6. Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening.
7. Known to have tested positive for human immunodeficiency virus
8. Current smokers with a smoking history of \> 10 pack-years. Current smokers with a smoking history of \< 10 pack-years are permitted . Ex-smokers should not have a smoking history \> 10 pack-years at screening. Participants who use e-cigarettes will also be excluded from the study.
9. Known history of drug or alcohol abuse within 1 year of screening
10. Any concomitant medications that are known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4).
11. History of QT prolongation associated with other medications that required discontinuation of that medication.
12. Congenital long QT syndrome.
13. Creatinine clearance \<50 ml/min (calculated by Cockcroft-Gault formula, reference Appendix G).
14. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding.
15. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.

Primary outcomes:
measure: Proportion of patients who have moderate and severe exacerbations of asthma
timeFrame: 90 Days post-treatment
Secondary outcomes:
measure: Numbers of subjects returning to ED
timeFrame: 90 Days post-treatment
measure: Proportion of subjects returning to ED
timeFrame: 60 Days post-treatment
measure: Asthma control Questionnaire (ACQ-5)
timeFrame: 90 Days post-treatment
measure: TSLP levels
timeFrame: Day 1
measure: IL-25 levels
timeFrame: Day 1
measure: Il-33 levels
timeFrame: Day 1
Other outcomes:
measure: Number of participants with treatment-related adverse events as assessed by an intensity rating scale
timeFrame: Through study completion, an average of 180 days
measure: Nasal brushing expressions of TSLP(Exploratory Outcome)
timeFrame: Day-30, 90 and 180 post ED visit
measure: Measure ACQ-5 at selected time-points (Exploratory Outcome)
timeFrame: Day-30, 90 and 180 post ED visit
measure: Measure pre-bronchodilator FEV1 at selected time points (exploratory outcome)
timeFrame: Day 30, 90 and 180 days post ED visit
measure: Measure TSLP expression at various time points Peripheral blood eosinophil counts FeNO Serum IgE (Exploratory Outcome)
timeFrame: Day 1
measure: FeNO will be tested at selected time-points (Exploratory Outcome)
timeFrame: Day 30, 90 and 180 post ED visit
measure: Nasal brushing expressions of IL-33 (Exploratory Outcome)
timeFrame: Day-30, 90 and 180 post ED visit
measure: Nasal brushing expressions of IL-25 (Exploratory Outcome)
timeFrame: Day-30, 90 and 180 post ED visit
measure: Measure pre-bronchodilator PEF at selected time points (exploratory outcome)
timeFrame: Day-30, 90 and 180 post ED visit
Locations:
city: St. Albert
country: Canada
facility: Sturgeon Community Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Ca-ab
Study officials:
affiliation: University of Alberta
name: Irvin Mayers, MD
role: PRINCIPAL_INVESTIGATOR
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