The Inflammatory Profile of Exacerbations in Patients With Severe Asthma Receiving Tezepelumab: The TezEx Study

NCT06666504 | Not Yet Recruiting

• 1 other identifier: 343080 TeZeX
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Tezepelumab is a treatment that is approved by NICE (National Institute for Health and Care Excellence, https://www.nice.org.uk/) for patients with severe asthma, that remains poorly controlled despite high dose inhaled glucocorticosteroid medication. The goal of this observational study is to learn why some patients with severe asthma continue to have asthma flare ups despite being on tezepelumab.

Conditions

Severe Asthma

Keywords

Tezepelumab; Anti-Asthmatic Agents; Respiratory System Agents; Pathologic Processes; Inflammation

Outcome Measures

Primary Outcomes (1)

• Change in blood and airway (sputum and nasosorption) levels of T1, T2, T17, or other pro-inflammatory mediators, biomarkers and/or cells including EPX (eosinophil peroxidase) measurements in patients with severe asthma treated with tezepelumab

  To investigate the changes in the number of inflammatory cells (in blood and airway) in patients with severe asthma treated with tezepelumab who experience an acute severe asthma exacerbation compared to stable state levels at one year post-initiation.

  From enrolment to one year post initiation of tezepelumab

Secondary Outcomes (7)

• Change in lung function parameters measured by spirometry (FEV1, FVC, FEV1/FVC)

  52 weeks

• Asthma control measured by Asthma Control Questionnaire (ACQ)-6

  52 weeks

• Change in exacerbation frequency at 4 weeks and 1 year compared to baseline

  52 weeks

• Oral steroid reduction at 4 weeks and 1 year compared to baseline

  52 weeks

• Change in routine full blood counts including eosinophil and serum total IgE at 4 weeks and 1 year compared to baseline

  52 weeks

Other Outcomes (5)

• To investigate blood transcriptomic differences between patients who achieve clinical and/or biological remission at one year compared to those who do not achieve remission on tezepelumab.

  1 year since tezepelumab initiation

• To investigate the differences in inflammatory mediators in nasal mucosal lining fluid at 1 year between patients in clinical and/or biologic remission and those not in remission on tezepelumab

  1 year since tezepelumab initiation

• To determine the change in number of immune cells at 1 year between patients in clinical and/or biologic remission and those not in remission on tezepelumab

  1 year since tezepelumab initiation

Study Arms (1)

All participants

All eligible participants will be consented and enrolled into the study.

Other: Combined Retrospective and Prospective Data Analysis

Interventions

Combined Retrospective and Prospective Data Analysis OTHER

Collection of both retrospective and prospective data all ready available for participant

All participants

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with poorly-controlled severe asthma who meet NICE criteria to commence/on biologic therapy with tezepelumab.

You may qualify if:

• Patients who qualify for tezepelumab according to NICE eligibility criteria and yet to begin treatment or those patients within 36 weeks (+/-8 weeks) since their first dose of tezepelumab at the Guy's severe asthma centre.
• Age ≥ 18 and ≤ 80 years at tezepelumab initiation.
• Able and willing to provide written informed consent and to comply with the study protocol, including being able to attend for assessment during a symptomatic deterioration.

You may not qualify if:

• Other clinically significant medical disease that is likely, in the opinion of the investigator, to require a change in biologic therapy or impact the ability to participate in the study.
• History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
• Other severe eosinophilic lung disease including EGPA, chronic eosinophilic pneumonia and ABPA
• Severe bronchiectasis on CT causing daily sputum production
• Maintenance therapy with an antibiotic including azithromycin or doxycycline
• Inability to give written informed consent

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator

Study Sites (1)

Guys & St Thomas NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Menzies-Gow A, Colice G, Griffiths JM, Almqvist G, Ponnarambil S, Kaur P, Ruberto G, Bowen K, Hellqvist A, Mo M, Garcia Gil E. NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020 Oct 13;21(1):266. doi: 10.1186/s12931-020-01526-6.

  PMID: 33050934 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum/ plasma/ cells (blood), sputum and nasal samples (airway)

MeSH Terms

Conditions

Asthma; Pathologic Processes; Inflammation

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathological Conditions, Signs and Symptoms

Study Officials

• David Jackson, PhD

  Guys & St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathew Clinical Trial Coordinator, MSc

CONTACT

+44 207 188 7188; mathew.furtado@gstt.nhs.uk

Gillian Radcliffe, MRes

CONTACT

+442071888070; gillian.radcliffe@gstt.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: October 30, 2024
• Study Start: December 1, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 30, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)