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

Phase 1

• 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-DK
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-23
• Last Update Posted: 14 December 2020

Recruitment & Eligibility

• Status: ot Recruiting
• 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
Main Objective: To explore the airway anti-inflammatory effect of tezepelumab;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;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<br>for the majority of subjects but may be performed at later timepoints for<br>some subjects (Week 32, etc.) due to up to 6 additional doses added<br>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<br>for the majority of subjects but may be performed at later timepoints for<br>some subjects (Week 32, etc.) due to up to 6 additional doses added<br>during the Covid-19 pandemic.