Severe asthma Respiratory Asthma
Conditions
Interventions
Participants will initially be screened and stratified into a severe asthma sub-group (either T2-High or T2-Low) using blood eosinophils levels. Participants will then be randomised into either the T2
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Stage 1 Screening, the trial population will consist of participants that are both: 1. Exacerbation prone (=2 record confirmed severe exacerbations) AND 2. Severe asthma (defined by a hospital specialist or severe asthma Multi-Disciplinary Team (MDT, or non-English equivalent), according to the ATS/ERS consensus criterion 3. Aged = 18 years and < 80 years 4. Capable of giving written informed consent 5. Willing and able to comply with study protocol requirements T2-High and T2-Low Inclusion Criteria: 1. Aged = 18 years and < 80 years 2. Capable of giving written informed consent 3. Diagnosis of severe asthma as per the ATS/ERS severe asthma guidelines. [Participants may be included with a lower dose of current ICS than endorsed by the ATS/ERS criteria at the discretion of the investigator if previous high ICS dose had led to side effects 4. Stable asthma therapy for at least 1 month before screening 5. Willing and able to comply with study protocol requirements 6. History of ‘exacerbation prone asthma’ defined as = two record confirmed severe exacerbations within 12 months of MDT initial pre-screening review. Defined as worsening asthma symptoms necessitating one or more of the following: 6.1. Use of systemic steroids (tablets, suspension or injection) or an increase in systemic steroids (for those on stable maintenance steroids) for = 3 days 6.2. New prescription of antibiotics because of worsening asthma/airways disease for = 3 days 6.3. Both 6.1. and 6.2. 6.4. Admission to hospital because of asthma, or an emergency department requiring systemic steroids (tablets, suspension or injection) or antibiotics [If any of the above are identified =7days apart, these would be defined as separate/new exacerbation events]
Exclusion criteria
Exclusion criteria: 1. Current or within the last 6 months (or maximum relevant wash out period, whichever is longer), participation in an investigational drug or device trial at the time of screening 2. Patients who are planning to take more than a 21 day consecutive holiday during the trial period 3. Have received treatment with biologics such as omalizumab, mepolizumab, reslizumab, benralizumab or dupilumab within four months or five half-lives (whichever is longer) prior to screening 4. Recent treatment with bronchial thermoplasty, defined as completion of all thermoplasty treatment sessions within 6 months of screening 5. Patients who have been hospitalised or required a new prescription of high-dose (=10mg prednisolone/day) oral corticosteroid (OCS) therapy within 4 weeks of the screening visit 6. Recent (within 4 weeks of screening) or current lower respiratory tract infection requiring antibiotics (this excludes antibiotics taken for other purposes other than asthma exacerbations) 7. Acute illness other than asthma which, in the investigator’s opinion, may compromise the well-being of the patient or study endpoint assessments at the start of the study 8. History of unstable or severe cardiac, hepatic, or renal disease, or other medically significant illness which the investigator believes would be a contraindication to study participation 9. Current smoking within the past year or a prior smoking history of =15 pack-years (including e-cigarettes) 10. Patients with a body mass index (BMI) = 17 or = 45 kg/m² 11. History of human immunodeficiency virus (HIV) or hepatitis B or C 12. History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, currently or within the past 5 years, regardless of whether there is evidence of local recurrence or metastases 13. History (or suspected history) of alcohol or substance abuse as defined by the Diagnostic and Statistical manual of mental Disorders (5th edition) substance use disorders guidelines within two years of screening 14. If female, is pregnant or lactating or intends to become pregnant during the study period where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test 15. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of trial treatment and for a minimum of 1 month after their last treatment 16. Males unwilling to use effective methods of contraception during dosing of trial treatment and for at least 3 months after their last dose 17. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening including (but not limited to): 17.1. AST or ALT>2.0x upper limit of normal (ULN) or total bilirubin >1.3 X ULN at screening (with the exception of patients with Gilberts syndrome where suitability for inclusion will be left to the discretion of the local investigator) 17.2. Estimated Glomerular Filtration Rate (eGFR) by the MDRD equation <60 mL/minute/1.73 m² at screening T2-High Specific Exclusion Criteria: 1. Treatment with pramipexole (Mirapex®) within 4 weeks of baseline 2. Patients where untreated infection with helminthic parasites is suspected by the clinician 3. Concomitant use of drugs known to be associated with significant neutropenia (see Appendix 7, for the list of drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annual rate of severe exacerbations defined as one or more of the following (using patient records): 1. Use of systemic steroids (tablets, suspension or injection) or an increase in systemic steroids (if stable maintenance) for equal to or greater than 3 days 2. A new prescription of antibiotics for worsening asthma/airways disease for equal to or greater than 3 days 3. Both 1 and 2 4. An admission to hospital because of asthma, or an emergency department requiring systemic steroids or antibiotics. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Assessing improvements in asthma symptoms is measured using the Juniper six-point Asthma Control Score (ACQ-6) measured at 3, 6, 9 and 12 months 2. Measuring health-related quality of life in trial participants is measured using the Juniper Asthma quality of life questionnaire AQLQ (S) measured at 3, 6, 9 and 12 months 3. Post bronchodilator FEV1 and FEV1/FVC measured at 3, 6, 9 and 12 months using spirometry 4. Absolute blood eosinophil and neutrophil levels (x109/L) measured at 3, 6, 9 and 12 months by taking blood samples from participants and performing full blood and differential cell counts 5. Percentage sputum eosinophils measured at 3, 6, 9 and 12 months through participant sputum samples obtained by sputum induction 6. Fractional exhaled nitric oxide levels (FeNO) in exhaled breath is measured at 3, 6, 9 and 12 months 7. Percentage and total sputum neutrophils measured at 3, 6, 9 and 12 months through participant sputum samples obtained by sputum induction 8. Testing the impact of chronic rhinosinusitis on the participant’s quality of life using Sino-nasal Outcome Test (SNOT-22) measured at 3, 6, 9 and 12 months 9. Measuring the participant’s subjective experience of severe asthma and the associated symptoms measured using VAS scale measured at 3, 6, 9 and 12 months 10. Assessing the health status of the participants using EuroQol Five Dimension EQ-5D-5L quality of life (Baseline and penultimate visit only i.e. Day 0 and Day 365) 11. Measuring the impairment that severe asthma in both paid and unpaid activities for the participants and is measured using the Work Productivity and Activity Impairment (WPAI) (Baseline and penultimate visit only i.e. Day 0 and Day 365) 12. Time to first severe exacerbation 13. Annual rate of severe exacerbation events defined by the use of systemic steroids, antibiotics or both 14. Adverse events measured by asking the participant to report all adverse events and any changes in adverse events at every scheduled trial visit | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactMirjana Sirovica
Outcome results
None listed