Adult patients with severe asthma with type 2 inflammation Respiratory
Conditions
Interventions
Patients will attend a screening visit to assess if inclusion/exclusion criteria are met and informed consent taken if the patient wants to participate. Their inhaled corticosteroid/long-acting beta a
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients, aged 18 to 75 years with severe GINA-defined asthma 2. Taking a medium to high dose of ICS/LABA OR high dose ICS with another second line controller (BDP equivalent dose of =800 µg) of step 4/5 GINA therapy. 3. Established diagnosis of persistent asthma for at least 6 months according to GINA guidelines. 4. Diagnosis should have been properly documented at the screening visit, based on medical documentation and medical history. 5. Uncontrolled asthma as per ACQ6 =1.5 6. Forced Expiratory Volume in 1 second (FEV1) =50% predicted at screening. 7. Mannitol PD10 =635 mg at Visit 1 8. Severe asthma with type 2 inflammation as evidenced by: 8.1. Eos =300 cells/µl at screening visit or within 6 months prior to screening OR 8.2. Eos =150 cells/µl with FeNO =25 ppb at screening visit or within 6 months prior to screening OR 8.3. FeNO =50 ppb at screening visit or within 6 months prior to screening 8.4. Eosinophil count and FeNO are not inclusion criteria in those patients already taking maintenance oral corticosteroids prior to trial recruitment 9. Ability to give informed consent. 10. Agreement for their GP to be made aware of study participation and to receive feedback as relevant to the participant’s wellbeing.
Exclusion criteria
Exclusion criteria: 1. Patient who has taken any biologic treatment for asthma within 3 months before V1. 2. Any other respiratory diseases such as COPD and moderate to severe bronchiectasis which in the opinion of the investigator are considered to be clinically significant and may have an impact on the study outcomes. Patients with Asthma COPD Overlap (ACO) may be included providing they meet all the other criteria. 3. Active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). 4. Any known systemic (e.g., blood, liver, kidney, etc.) clinically significant medical condition, known significant laboratory abnormalities or communicable disease that may endanger the health or safety of the patient. 5. Asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month prior to screening visit or 3 months if hospital admission was required. 6. Any disorder that is not stable in the opinion of the Investigator. 7. Patients who are participating in the clinical phase of another interventional trial or have done so within the last 30 days or within 5 half-lives of the previous administered product (whichever is longer) before screening. Individuals who are participating in the follow-up phase of another interventional trial, or who are enrolled in an observational study, will be co-enrolled where the Coordinating Investigator of each study agree that it is appropriate. 8. Female patients who are pregnant or lactating. 9. Patients unable or unwilling to consent. 10. Patients taking non-permitted medications. 11. Patients with a history of hypersensitivity to any of the study medications components or a history of other allergy that in the opinion of the investigator contraindicates the patient's participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Airway hyperresponsiveness measured by mannitol challenge as the provocative dose causing a 10% fall in FEV1 (PD10 Mannitol) at Visits 1-5 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mannitol response dose ratio (RDR) will be assessed by mannitol challenge at Visits 1-5. 2. Number of puffs of maintenance and reliever therapy (MART) required as recorded on patient diary cards will be assessed at Visits 1-5 and at 3 injection-only visits. 3. Type 2 biomarkers: Fractional exhaled nitric oxide (FeNO) will be measured with a pulmonary function test and blood eosinophils will be measured with a blood test at screening and Visits 1-5. Blood eosinophil derived neurotoxin (EDN) will be measured with a blood test at Visits 1-5. 4. Spirometry and airway oscillometry pulmonary function tests will be performed at screening and at Visits 1-5. 5. Asthma control questionnaire (ACQ6) and mini-asthma quality of life questionnaire (mini-AQLQ) scores will be assessed with questionnaire completion at screening and Visits 1-5. 6. Domiciliary peak expiratory flow (PEF), asthma symptoms, and reliever use will be recorded either electronically or on daily patient diary cards and will be collected at Visits 1-5 and at 3 injection-only visits. Exploratory Outcome measures: 7. Nasal symptoms and peak nasal inspiratory flow (PNIF) as recorded on patient diary cards will be collected at Visit 1, Visit 4 and Visit 5. 8. Nasal nitric oxide test will be performed at Visit 1, Visit 4 and Visit 5. 9. Sino-nasal outcome test (SNOT-22) patient questionnaires will be completed at Visit 1, Visit 4 and Visit 5. | — |
Countries
Scotland, United Kingdom
Outcome results
None listed