A Phase 2 Study to Evaluate the Effect of Tezepelumab on Airway Inflammation in Adults with uncontrolled asthma

Phase 1

Active, not recruiting

• Conditions: Severe Asthma; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2018-002069-21-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-25
• Last Update Posted: 15 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

- Subject must be 18 to 75 years of age
- Documented physician-diagnosed asthma for at least 12 months
- Subjects who have received a physician- prescribed asthma controller medication with medium or high dose ICS for at least 12 months; must be stable for at least 3 months prior to screening visit
- At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months
-At enrolment, the subject must have a predicted normal value for the morning pre-bronchodilator FEV1>50% and more than 1L
- Evidence of asthma as documented by reversibility of FEV1 =12% and =200 mL in the previous 12 months prior to screening, or during the screening period prior to randomization
- ACQ-6 score = 1.5 during the screening period prior to randomization
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

- Any clinically important pulmonary disease other than asthma
- History of cancer
-Hospitalization or required OCS for asthma exacerbation within 6 weeks of enrolment or >3 exacerbations requiring OCS or hospitalization in the year prior to visit 1 or who had been intubated or admitted to ICU for asthma exacerbation in the year prior to enrolment
- History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with
antibiotics or antiviral medications finalized <2 weeks before visit 1 or during the run-in period.
- Current smokers or subjects with smoking history =10 pack-yrs, including e-cigarettes. Former smokers with a smoking history of <10
pack-yrs must have stopped for at least 6 months prior to visit 1, including e-cigarette use.
- History of chronic alcohol or drug abuse within 12 months prior to visit 1.
-Tuberculosis requiring treatment within 12 months prior to visit 1.
-History of known immunodeficiency disorder including a positive HIV test at visit 1, or the subject is taking antiretroviral medications as
determined by medical history and/or subject's verbal report
- History of anaphylaxis or documented immune complex disease (type III hypersensitivity reactions) following any biologic therapy.
- Subject randomized in a previous Tezepelumab study or in a current study with another investigational product.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1. To explore the effect of tezepelumab on reticular basement membrane (RBM) thickening<br>2. To explore the effect of tezepelumab on airway epithelial integrity<br>3. To explore the airway anti-inflammatory effect of tezepelumab across the spectrum of T2 status by three gene mean derived from epithelial brushing RNA transcriptomics;Main Objective: To explore the airway anti-inflammatory effect of tezepelumab;Primary end point(s): The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.;Timepoint(s) of evaluation of this end point: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies<br> <br>2. The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies <br><br>3. The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies;Timepoint(s) of evaluation of this end point: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.