An observational study in Severe Asthma, sponsored by Guy's and St Thomas' NHS Foundation Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-06-29.
Sponsored by Guy's and St Thomas' NHS Foundation Trust · Observational
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.
Asthma is one of the most common chronic respiratory conditions in the world and is characterized by a diverse range of symptoms, including wheezing, shortness of breath, chest tightness, and cough, which vary over time. Among the asthmatic population, 3.6% have severe asthma, enduring persistent symptoms and uncontrolled disease despite adhering to high-dose inhaled therapy. They experience recurrent exacerbations and substantial steroid exposure as well as a poor quality of life, frequently leading to hospital admissions and heightened healthcare utilization.
Recent years have witnessed a concentrated effort to explore various inflammatory pathways implicated in asthma exacerbations. Thymic stromal lymphopoietin (TSLP), identified as an alarmin, plays a crucial role in type 2 immune responses and the promotion of T helper 2 (TH2) cell-mediated diseases, including asthma and atopic dermatitis. Research indicates that TSLP, released in response to airway epithelial stress induced by allergens, viruses, and airborne particles, serves as a key upstream mediator of the inflammatory response, influencing both T2 cytokine expression and asthma severity.
Tezepelumab, a human monoclonal antibody targeting TSLP activity, has demonstrated efficacy in reducing asthma exacerbations, improving asthma control and lung function in controlled studies including the NAVIGATOR and PATHWAY studies. Acting upstream in the inflammatory cascade, tezepelumab exhibits the ability to decrease T2 biomarkers such as FeNO, blood eosinophil, and IgE, suggesting its potential to suppress multiple pathways rather than focusing on a single downstream mediator. The CASCADE trial further supports TSLPs mechanistic roles by revealing a decrease in airway hyperresponsiveness and mucus plugging, suggesting additional benefits beyond the reduction of type 2 airway inflammation.
However, despite reduction eosinophil count and other T2 biomarkers, our real-world experience has shown that certain patients continue to have an exacerbation risk on tezepelumab.
A recent study showed that children established on anti-IL-5 therapy for severe asthma had eosinophil subpopulations to be significantly elevated in the airway that could contribute to exacerbations. It is unclear if the same or other inflammatory pathways continue to remain active in patients on anti-TSLP therapy as studies to explore this have not been conducted on tezepelumab.
This projects primary aim is to investigate the clinical, physiological and inflammatory characteristics of asthma exacerbations that persist despite tezepelumab therapy in patients with severe asthma.
Study Hypothesis:
In patients with severe uncontrolled asthma, who have been established on tezepelumab, asthma exacerbations may reflect both persistent T2 and non-T2 driven events.
Adult patients with poorly-controlled severe asthma who either meet NICE criteria to begin biologic therapy with tezepelumab or within 36 weeks of being established on it will be invited to participate in the study at Guys Severe Asthma Centre. Tezepelumab will be given according to UK NICE severe asthma guidance with 210mg sc dosing every 4 weeks. 150 participants will be recruited and followed up for 48 weeks (until they complete one year on tezepelumab).
These potential participants will receive written information about the study in the form of a patient information sheet (PIS). The patient would be adviced to contact the clinical team when there is a deterioration in their asthma control. These patient will then have further assessments performed alongwith tests when seen in person.
The study is exploratory and will assess deteriorations in asthma control (exacerbations) to characterise the clinical severity of each exacerbation and the airway and systemic inflammatory phenotype associated with these events. Clinical assessment and management of each exacerbation will be in line with standard clinical guidelines.
At all visits unless otherwise stated, the following will be collected (not limited to):
Clinical observations Information regarding their asthma symptoms and adverse events Clinical examination (if required) Asthma control score and quality of life questionnaire (ACQ-6) Blood samples will be collected and breathing tests will be performed (spirometry, fractional exhaled nitric oxide (FeNO)).
In patients who have had deterioration in asthma control, will have blood, nasal and sputum samples collected at their exacerbation visit and stable state at one year. The above samples will also be collected for a group (\~25) of patients who remain in clinical and/or biological remission on tezepelumab at the end of one year.
4,841 studies on the registry are indexed under Asthma; 600 are open to participants now.
This study's enrollment of 150 is close to the median of 158 across 1,250 observational studies indexed under Asthma.
Browse Asthma studies →Guy's and St Thomas' NHS Foundation Trust is the lead sponsor of 295 studies on the registry; 80 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adult patients with poorly-controlled severe asthma who meet NICE criteria to commence/on biologic therapy with tezepelumab.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All eligible participants will be consented and enrolled into the study.
Other: Prospective Data Analysis
Collection of both retrospective and prospective data available for each participant
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.
Time frame: From enrolment to one year post initiation of tezepelumab
Change in lung function parameters measured by spirometry (FEV1, FVC, FEV1/FVC)
Change in lung function parameters at 4 weeks and 1 year compared to baseline of treatment measured by spirometry (FEV1, FVC, FEV1/FVC)
Time frame: 52 weeks
Asthma control measured by Asthma Control Questionnaire (ACQ)-6
Change in asthma control questionnaire at 4 weeks and 1 year compared to baseline of treatment. Total score ranges from 0-6, with 0=no impairment due to asthma, 6 = maximum impairment due to asthma.
Time frame: 52 weeks
Change in exacerbation frequency at 4 weeks and 1 year compared to baseline
Exacerbation frequency (number of exacerbations at baseline / during treatment)
Time frame: 52 weeks
Oral steroid reduction at 4 weeks and 1 year compared to baseline
Proportion of patients who reduce dose/wean off maintenance steroid dose (in milligrams)
Time frame: 52 weeks
Change in routine full blood counts including eosinophil and serum total IgE at 4 weeks and 1 year compared to baseline
Change in routine full blood counts including eosinophil and serum total IgE at 4 weeks and 1 year compared to baseline
Time frame: 52 weeks
Change in FeNO levels at 4 weeks and 1 year compared to baseline
FeNO will be measured in parts per billion (ppb)
Time frame: 52 weeks
Proportion achieving clinical and biologic remission at 1 year
Definition of Clinical Remission: * No asthma exacerbation in the 12 months since commencing tezepelumab * No ongoing maintenance OCS for asthma * ACQ-6 score less than 1.5 Litre * FEV1 (post bronchodilator) - less than 5% decline 1 year after starting tezepelumab Definition of biologic remission: FeNO less than 25ppb AND blood eosinophils less than 150 cells/mcL
Time frame: 1 year since tezepelumab initiation
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.
Gene expression will be measured using RNA sequencing and reported as gene counts
Time frame: 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
Nasosoprtion samples will be collected to assess changes in proinflammatory cytokines/chemokines measured in pg/ml.
Time frame: 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
To determine the change in number of immune cells by using mass cytometry (CyTOF)
Time frame: 1 year since tezepelumab initiation
To determine the activation status of immune cells at 1 year between patients in clinical and/or biologic remission and those not in remission on tezepelumab
To determine the activation status in of immune cells as measured by by using mass cytometry (CyTOF)
Time frame: 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
To determine the change in number of immune cells by using protein analysis (ELISA)
Time frame: 1 year since tezepelumab initiation
Plan to share: No — No individual participant data will be shared or made available to researchers outside of the site research team where the patient is based, and GSTT asthma research team.
This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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