Biomarkers of asthma remission after dupilumab treatment
| ISRCTN | ISRCTN68147929 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68147929 |
| IRAS number | 320731 |
| Secondary identifying numbers | UoL0870, IRAS 320731, CPMS 55224 |
- Submission date
- 09/05/2023
- Registration date
- 12/05/2023
- Last edited
- 28/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Asthma affects over 350 million people in the world. Approximately 5-10% of people with asthma have severe disease. Asthma is a lung disease associated with inflammation (swelling) of the airways. Certain proteins made by the body, called interleukins, can make this inflammation worse. One of these interleukin proteins is called interleukin- 4Rα (IL4Rα). Interleukin-4Rα appears to play an important role in asthma. It plays a role by helping white blood cells (called eosinophils) stay alive. Eosinophils are involved in the inflammation of the airways. Dupilumab is a medicine that blocks the effect of Interleukin-4Rα on eosinophils (and therefore reduces inflammation). It is given as an injection under the skin and may help reduce inflammation in the airways of people with asthma. Previous research studies in people with severe asthma have shown an improvement in asthma control in those who received dupilumab, and it is now approved for the treatment of severe asthma in the UK. Research studies have shown that people who received dupilumab experienced about half as many asthma exacerbations (severe episodes of asthma or attacks) as those given placebo (dummy) injections. In addition, it also improved their lung function and asthma control. This research study will observe all participants having dupilumab injections as part of their normal clinical care. This will help to understand what might be causing the high levels of disease control, including the absence of symptoms and exacerbations. By doing this, it is hoped that information will be obtained to help improve asthma treatment in the future. The study team will investigate the effect of dupilumab on all aspects of asthma such as changes in quality of life, symptoms, inflammation and breathing tests.
Who can participate?
Adults (≥18 years old) following a clinical decision to initiate dupilumab for severe asthma after meeting licensing, local and national guidelines.
What does the study involve?
Every participant taking part in the study will be receiving dupilumab injections as part of their normal clinical care. Participants will be asked to attend a total of 5 scheduled visits at the study centre. Visit 0 and Visit 1 can be combined where feasible to do so. In between study visits, participants will be asked to complete some breathing tests at home. They will be asked to monitor their peak flow (maximum rate a person can breathe out) and a test for exhaled nitric oxide (FeNO) every day for the first 4 weeks of the study and then once a week afterwards. This is to monitor the usual variation in their asthma symptoms and airway function, and how this might change if they become unwell.
What are the possible benefits and risks of participating?
There is no guarantee that participants will receive any benefit from this study, and taking part in this study may or may not improve their asthma. Information from this study may help asthma treatment in the future. There are possible risks, disadvantages and inconveniences with any research study. The individual risks of each procedure and investigation are described fully in the participant information sheet. Participants will potentially have more tests and procedures if they take part in the study, compared to standard hospital visits. Study visits could take more time than standard hospital visits and you will have more blood taken. Each study visit can last approximately 1-3 hours. Participants will have to do additional monitoring of their asthma at home as the study requires them to keep track of their peak flow reading and lung inflammation with FeNO (approximately 10 minutes).
Where is the study run from?
This is a research project organised by the NIHR Leicester Biomedical Research Centre – Respiratory, at Glenfield Hospital. This study is part of a larger programme of studies, called 3TR. 3TR is a European research group aimed at improving the treatment of asthma and chronic obstructive pulmonary disease (COPD). This study is being conducted by a group of clinical and academic experts from UK universities and Europe, together with pharmaceutical companies who have an interest in asthma. The sponsor of the study is the University of Leicester, UK. The sponsor is the organisation responsible for ensuring that the study is carried out correctly.
Who is funding the study?
Sanofi, the pharmaceutical company that makes dupilumab, is supporting the research by providing funding to the research units to carry out the study tests.
When is the study starting and how long is it expected to run for?
March 2023 to August 2026
Who is the main contact?
UK project management team, abc-3tr@leicester.ac.uk
Chief Investigator, Prof Chris Brightling, abc-3tr@leicester.ac.uk
Contact information
Public
Department of Respiratory Sciences
University of Leicester
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
| Phone | +44 (0)116 252 2893 |
|---|---|
| abc-3tr@leicester.ac.uk |
Principal Investigator
Department of Respiratory Sciences
University of Leicester
NIHR Leicester Biomedical Research Centre – Respiratory
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
 ORCID ID |
0000-0002-9345-4903 |
|---|---|
| Phone | +44 116 250 2704 |
| abc-3tr@leicester.ac.uk |
Study information
| Study design | Multi-centre, multi-national observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Biomarkers and mechanisms of asthma remission following treatment with dupilumab in adults with severe asthma – 3TR ABC |
| Study acronym | DUPIBIO – 3TR ABC |
| Study hypothesis | Asthma remission following treatment with dupilumab is related to baseline phenotype and biomarker(s) or early changes in biomarkers. |
| Ethics approval(s) |
Approved 13/04/2023, East Midlands – Nottingham 1 (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 207 104 8089; nottingham1.rec@hra.nhs.uk), ref: 23/EM/0031 |
| Ethics approval additional information | Approved 13/04/2023, East Midlands - Nottingham Research Ethics Committee 1 (Health Research Authority, 2nd Floor, Equinox House, City link, Nottingham, NG2 4LA, UK; +44(0)2078115; nottingham1.rec@hra.nhs.uk), ref: 23/EM/0031 |
| Condition | Severe asthma |
| Intervention | DUPIBIO – 3TR ABC is a multi-centre observational study of patients with severe asthma following initiation of treatment with dupilumab (anti-IL4Rα) as part of their standard of care. Participants will be extensively characterised at baseline; reviewed throughout the year with formal clinical and biological assessment at 4, 16 and 52 weeks. Asthma remission will be defined for each domain: asthma control, lung function, and exacerbations as a composite measure and independently. Biomarkers and multi-omic analysis will be undertaken in the biosamples to determine biological pathways and bio-signatures associated with asthma remission. This study is one of three arms aligned to the 3TR (taxonomy, treatment, targets and remission) EU-IMI consortium asthma biologics consortium (3TR-ABC). The primary objective is to determine baseline biomarkers of remission after 1 year of biological therapy, with remission defined as ACQ-5 <1.5, post-bronchodilator FEV1 percent predicted ≥80% OR >10% improvement, as well as no exacerbations. The secondary objectives are to determine baseline and short-term biomarkers of long-term remission after 1 year of biological therapy. Additionally: 1. Change in biomarker profiles in remission versus non-remission groups 2. Baseline and change in biomarker profile for 2.1. Each response outcome individually 2.2. Global evaluation treatment efficacy (GETE), Patient and physician-rated response-defined response 2.3. The 3TR agreed composite assessment of response 2.4. Change in profiles from baseline to 4 and 16 weeks as a predictor of remission 3. Determine the change in all response variables against baseline biomarker data and change in biomarkers as continuous variables. |
| Intervention type | Other |
| Primary outcome measure | Primary outcome measures are assessed at 1 year: 1. Asthma control measured using the Asthma Control Questionnaire 5 Questions (ACQ5) <1.5 2. Lung function post-bronchodilator (post-BD) Forced Expiratory Volume in 1 Second (FEV1) percent predicted measured using spirometry 3. Exacerbations history measured using the patient's medical notes |
| Secondary outcome measures | Current secondary outcome measures as of 30/07/2024: 1. Patient-reported outcomes: 1.1. Asthma Control Questionnaire 5 Questions (ACQ5), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.2. The Asthma Quality of Life Questionnaire (AQLQ), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.3. Self-Assessment Questionnaire (SAQ), assessed at visit 1 (week 0), Visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.4. EQ5D5L health status questionnaire, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.5. Work Productivity and Activity Impairment Questionnaire General Health (WPAI:GH), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.6. Sino-Nasal Outcome Test-22 Questionnaire (SNOT22), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.7. Nijmegen Questionnaire (NQ), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.8. Epworth Sleepiness Scale (ESS), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.9. Hospital Anxiety and Depression Scale (HADS), assessed visit 1 (week 0), visit 2 (week 2), visit 3 (week 16), visit 4 (week 52). 1.10. Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.11. Cognitive Failures Questionnaire, Screen for Cognitive Impairment in Psychiatry (SCIP), Trail Making test (TMT) part B (specific sites), assessed at visit 1 (week 0), visit 3 (week 16) and visit 4 (week 52). 1.12. Global evaluation treatment efficacy (GETE), patient and physician-related response, assessed at visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.13. Visual analogue scale (VAS) scale 3TR question (patient and physician perceived), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.14. Symptoms VAS, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52) and unscheduled exacerbation visit at sites where feasible/applicable. 2. Lung function: 2.1. Pre and post BD spirometry, assessed at visit 1 (week 0). 2.2. Post BD Forced Expiratory Volume in 1 Second (FEV1) assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3. Biomarkers: 3.1. Blood: differential cell count, total IgE and transcriptome (and in a subgroup scRNA), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). Specific IgE if not done with skin prick tests (cat dander, dog dander, house dust mite, grass pollen and Aspergillus IgE) and immunophenotyping, methylome (DNA collected for possible later eQTL analyses depending upon transcriptome data), assessed at visit 1 (week 0). 3.2. Nasal sampling: nasal brushings, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.3. Breath: 3.3.1. FeNO is assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit. 3.3.2. Breathomics is assessed at visit 1 (week 0), visit 2 (week 4), and visit 4 (week 52). 3.4. Sputum: cell differential, transcriptome, micro/metagenomics and proteomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.5. Saliva: Microbiome analysis and DNA, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.6. Urine: Urinary lipid mediators and metabolomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.7. Stool (optional): micro/metagenomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.8. Bronchoscopy (optional): brush biopsy, bronchial biopsies and broncho-alveolar lavage (BAL) for transcriptome, protein, micro/metagenomics, cellular and structural analyses, assessed at visit 1 (week 0) and visit 4 (week 52). 3.9. Mucosal biopsies: histological analysis of cells and inflammatory mediators, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). _____ Previous secondary outcome measures as of 19/01/2024: 1. Patient-reported outcomes: 1.1. Asthma Control Questionnaire 5 Questions (ACQ5), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.2. The Asthma Quality of Life Questionnaire (AQLQ), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.3. Self-Assessment Questionnaire (SAQ), assessed at visit 1 (week 0), Visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.4. EQ5D5L health status questionnaire, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.5. Work Productivity and Activity Impairment Questionnaire General Health (WPAI:GH), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.6. Sino-Nasal Outcome Test-22 Questionnaire (SNOT22), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.7. Nijmegen Questionnaire (NQ), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.8. Epworth Sleepiness Scale (ESS), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.9. Hospital Anxiety and Depression Scale (HADS), assessed visit 1 (week 0), visit 2 (week 2), visit 3 (week 16), visit 4 (week 52). 1.10. Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.11. Cognitive Failures Questionnaire, Screen for Cognitive Impairment in Psychiatry (SCIP), Trail Making test (TMT) part B (specific sites), assessed at visit 1 (week 0), visit 3 (week 16) and visit 4 (week 52). 1.12. Global evaluation treatment efficacy (GETE), patient and physician-related response, assessed at visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.13. Visual analogue scale (VAS) scale 3TR question (patient and physician perceived), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.14. Symptoms VAS, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52) and unscheduled exacerbation visit at sites where feasible/applicable. 2. Lung function: 2.1. Pre and post BD spirometry, assessed at visit 1 (week 0). 2.2. Post BD Forced Expiratory Volume in 1 Second (FEV1) assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3. Biomarkers: 3.1. Blood: differential cell count, total IgE and transcriptome (and in a subgroup scRNA), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). Specific IgE if not done with skin prick tests (cat dander, dog dander, house dust mite, grass pollen and Aspergillus IgE) and immunophenotyping, methylome (DNA collected for possible later eQTL analyses depending upon transcriptome data), assessed at visit 1 (week 0). 3.2. Nasal sampling: nasal brushings, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.3. Breath: Fractional exhaled nitric oxide (FeNO) and breathomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.4. Sputum: cell differential, transcriptome, micro/metagenomics and proteomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.5. Saliva: Microbiome analysis and DNA, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.6. Urine: Urinary lipid mediators and metabolomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.7. Stool (optional): micro/metagenomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.8. Bronchoscopy (optional): brush biopsy, bronchial biopsies and broncho-alveolar lavage (BAL) for transcriptome, protein, micro/metagenomics, cellular and structural analyses, assessed at visit 1 (week 0) and visit 4 (week 52). 3.9. Mucosal biopsies: histological analysis of cells and inflammatory mediators, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). _____ Previous secondary outcome measures as of 09/08/2023: 1. Patient-reported outcomes: 1.1. Asthma Control Questionnaire 5 Questions (ACQ5), assessed at visit 1 (week 0), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 1.2. The Asthma Quality of Life Questionnaire (AQLQ), assessed at visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.3. Self-Assessment Questionnaire (SAQ), assessed at visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.4. EQ5D5L health status questionnaire, assessed at visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.5. Work Productivity and Activity Impairment Questionnaire General Health (WPAI:GH), assessed visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.6. Sino-Nasal Outcome Test-22 Questionnaire (SNOT22), assessed visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.7. Nijmegen Questionnaire (NQ), assessed visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.8. Epworth Sleepiness Scale (ESS), assessed visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.9. Hospital Anxiety and Depression Scale (HADS), assessed visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.10. Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, assessed at visit 1 (week 0), visit 3 (week 16), visit 4 (week 52). 1.11. Cognitive Failures Questionnaire, Screen for Cognitive Impairment in Psychiatry (SCIP), Trail Making test (TMT) (specific sites), assessed at visit 1 (week 0), visit 3 (week 16) and visit 4 (week 52). 1.12. Global evaluation treatment efficacy (GETE), patient and physician-related response, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.13. Visual analogue scale (VAS) scale 3TR question (patient and physician perceived), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 2. Lung function: 2.1. Pre and post BD spirometry, assessed at visit 1 (week 0). 2.2. Post BD Forced Expiratory Volume in 1 Second (FEV1) assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3. Biomarkers: 3.1. Blood: differential cell count, total IgE and transcriptome (and in a subgroup scRNA), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). Specific IgE if not done with skin prick tests (cat dander, dog dander, house dust mite, grass pollen and Aspergillus IgE) and immunophenotyping, methylome (DNA collected for possible later eQTL analyses depending upon transcriptome data), assessed at visit 1 (week 0). 3.2. Nasal sampling: nasal brushings, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.3. Breath: Fractional exhaled nitric oxide (FeNO) and breathomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.4. Sputum: cell differential, transcriptome, micro/metagenomics and proteomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.5. Oral gargle: Microbiome analysis, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.6. Urine: Urinary lipid mediators and metabolomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.7. Stool (optional): micro/metagenomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.8. Bronchoscopy (optional): brush biopsy, bronchial biopsies and broncho-alveolar lavage (BAL) for transcriptome, protein, micro/metagenomics, cellular and structural analyses, assessed at visit 1 (week 0) and visit 4 (week 52). 3.9. Mucosal biopsies: histological analysis of cells and inflammatory mediators, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). _____ Previous secondary outcome measures: 1. Patient-reported outcomes: 1.1. Asthma Control Questionnaire 5 Questions (ACQ5), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 1.2. The Asthma Quality of Life Questionnaire (AQLQ), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.3. Self-Assessment Questionnaire (SAQ), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.4. EQ5D5L health status questionnaire, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.5. Work Productivity and Activity Impairment Questionnaire (WPAI), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.6. Sino-Nasal Outcome Test-22 Questionnaire (SNOT22), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.7. Nijmegen Questionnaire (NQ), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.8. Epworth Sleepiness Scale (ESS), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.9. Hospital Anxiety and Depression Scale (HADS), assessed visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.10. Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.11. Cognitive Failures Questionnaire, Screen for Cognitive Impairment in Psychiatry (SCIP), Trail Making test (TMT) (specific sites), assessed at visit 1 (week 0), visit 3 (week 16) and visit 4 (week 52). 1.12. Global evaluation treatment efficacy (GETE), patient and physician-related response, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 1.13. Visual analogue scale (VAS) scale 3TR question (patient and physician perceived), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 2. Lung function: 2.1. Pre and post BD spirometry, assessed at visit 1 (week 0). 2.2. Post BD Forced Expiratory Volume in 1 Second (FEV1) assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3. Biomarkers: 3.1. Blood: differential cell count, total IgE and transcriptome (and in a subgroup scRNA), assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). Specific IgE if not done with skin prick tests (cat dander, dog dander, house dust mite, grass pollen and Aspergillus IgE) and immunophenotyping, methylome (DNA collected for possible later eQTL analyses depending upon transcriptome data), assessed at visit 1 (week 0). 3.2. Nasal sampling: nasal brushings, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.3. Breath: Fractional exhaled nitric oxide (FeNO) and breathomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.4. Sputum: cell differential, transcriptome, micro/metagenomics and proteomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.5. Oral gargle: Microbiome analysis, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.6. Urine: Urinary lipid mediators and metabolomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52), and unscheduled exacerbation visit at sites where feasible/applicable. 3.7. Stool (optional): micro/metagenomics, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). 3.8. Bronchoscopy (optional): brush biopsy, bronchial biopsies and broncho-alveolar lavage (BAL) for transcriptome, protein, micro/metagenomics, cellular and structural analyses, assessed at visit 1 (week 0) and visit 4 (week 52). 3.9. Mucosal biopsies: histological analysis of cells and inflammatory mediators, assessed at visit 1 (week 0), visit 2 (week 4), visit 3 (week 16), visit 4 (week 52). |
| Overall study start date | 01/03/2023 |
| Overall study end date | 31/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 150 |
| Participant inclusion criteria | 1. Adults (≥18 years old) 2. Clinical decision to initiate dupilumab for severe asthma after meeting licensing, local and national guidelines. 3. Be able to give valid written consent. Participants should have reasonable understanding of the English language (assessed by the research team) 4. Be compliant with study procedures and study visits. |
| Participant exclusion criteria | 1. Known hypersensitivity to the active substance of dupilumab or any of the excipients 2. Participation in an interventional clinical trial within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half-lives. Participation in other observational studies is acceptable if, in the view of the investigator, it will not impact the study outcomes. 3. Other clinically significant medical disease or uncontrolled concomitant disease that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study. 4. Subjects on regular oral corticosteroids (OCS) and whereby the administration of dupilumab for OCS reduction will not be included in the study. |
| Recruitment start date | 31/08/2023 |
| Recruitment end date | 31/05/2025 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
Study participating centres
Groby Rd
Leicester
Leicester
LE3 9QP
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Gartnavel Royal Hospital
1055 Great Western Road Glasgow
Glasgow
G12 0XH
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
London
SW3 6NP
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
University/education
Research & Enterprise Division
Research Governance Office
University of Leicester
University Road
Leicester
LE1 7RH
England
United Kingdom
| Phone | +44 (0)116 373 6508 |
|---|---|
| RGOsponsor@le.ac.uk | |
| Website | https://le.ac.uk/research/regi |
"ROR" |
https://ror.org/04h699437 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- sanofi-aventis, Sanofi US, Sanofi-Aventis U.S. LLC, Sanofi U.S.
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/08/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | A publication plan will be written by the Trial Management Group (TMG) and the Patient and Public Involvement (PPI) group during the study with sponsor and funder approvals. It is envisaged that the results of the study will be published in newsletters and presented in public webinars for participants, lay media and relevant peer-reviewed journals. Individual responses to dupilumab will be provided by the local clinical teams to the participants as part of their standard of care. |
| IPD sharing plan | The datasets generated and/or analysed during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
28/02/2025: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2024 to 31/05/2025.
2. The overall end date was changed from 31/03/2026 to 31/08/2026.
3. The intention to publish date was changed from 31/03/2027 to 31/08/2028.
4. The plain English summary was updated to reflect these changes.
12/08/2024: The recruitment end date was changed from 31/08/2024 to 31/12/2024.
30/07/2024: The following changes were made to the trial record:
1. The secondary outcome measures were changed.
2. The sponsor address was changed.
19/01/2024: The following changes were made to the trial record:
1. The secondary outcome measures were changed.
2. The study participating centre Royal Brompton Hospital was removed and Guy's and St Thomas' NHS Foundation Trust added.
09/08/2023: The following changes were made to the trial record:
1. The secondary outcome measures were changed.
2. The recruitment start date was changed from 01/08/2023 to 31/08/2023.
3. The study participating centres Imperial College Healthcare NHS Trust, Oxford University Hospitals were removed and Cambridge University Hospitals NHS Foundation Trust, Royal Brompton Hospital were added.
05/06/2023: Internal review.
02/06/2023: Contact details updated.
12/05/2023: Trial's existence confirmed by the HRA and Health and Care Research Wales (HCRW) (UK).
