T2-High and T2-Low severe asthma MedDRA version: 20.1 Level: LLT Classification code 10005503 Term: Blood eosinophils System Organ Class: 100000004848 MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 21.1 Level: LLT Classification code 10049868 Term: Asthma exacerbation prophylaxis System Organ Class: 100000004865 MedDRA version: 21.1 Level: LLT Classification code 10068462
Conditions
Interventions
Product Name: Dexpramipexole
Product Code: KNS-760704
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexpramipexole
CAS Number: 104632-28-2
Current Sponsor code: KNS-760704
Other descriptive name:
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening Eligibility Criteria: 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. Male and female patients aged =18 years and 7 days apart, these would be defined as separate/new exacerbation events]. 7. Willing and able to comply with study protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
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 2 highly effective forms of contraception during dosing of study 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): • AST or ALT>2.0 x 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). • Estimated Glomerular Filtration Rate (eGFR) by the MDRD equation <60 mL/minute/1.73 m2 at screening. Additional Exclusion criteria for T2-LOW only: 1.Patients who are unwilling to stay out of the sun or wear sun block. 2.History of myasthenia gravis or systemic lupus erythematosus. 3.Prior history of ‘severe’ (as defined by the patient), gastrointestinal intolerance to tetracyclines. 4.Documented drug allergy to/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (i) Identify patients with severe, exacerbation prone asthma in UK specialist severe asthma centres. (ii) Stratify patients using blood eosinophil levels into T2-HIGH/T2-LOW phenotypes. (iii) Conduct two 58 week, phase II, randomised double blind placebo controlled exacerbation trials (RDBPCT) of oral dexpramipexole (T2-HIGH) and oral doxycycline (T2-LOW). ;Secondary Objective: Patients in both T2 HIGH/LOW treatment cohort randomised controlled trials will be assessed for change from baseline at 3, 6, 9 and 12 months for: • Juniper six-point Asthma Control Score (ACQ-6, a questionnaire to determine how well controlled asthma symptoms are through current medication) • Asthma Quality of Life Questionnaire (AQLQ S, a quality of life questionnaire specifically focused on asthma symptoms) • Asthma follow up and lung function tests • Blood eosinophil levels (blood results which determines which asthma sub-type the participant has and whether this is affected by treatment) • Blood neutrophil levels (blood cells which help fight off infection and can be an indication of infection) • Percentage sputum eosinophils (see blood eosinophil levels) • Percentage and total sputum neutrophils (see blood neutrophil levels) • Sino-nasal Outcome Test (SNOT-22, a questionnaire to determine nasal issues in participants) • EuroQOL-5D-5L Questionnaire (baseline and penultimate vi;Primary end point(s): Annual rate of severe exacerbations defined as one or more of: (i) Use of systemic steroids (tablets, suspension or injection) or an increase in systemic steroids (if stable maintenance) for =3 days (ii) A new prescription of antibiotics for worsening asthma/airways disease for =3 days (iii) Both (i) and (ii) (iv) An admission to hospital because of asthma, or an emergency department requiring systemic steroids or antibiotics;Timepoint(s) of evaluation of this end point: The end point of this primary outcome measure is 13.5 months after the patient has been registered to | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Juniper six-point Asthma Control Score (ACQ-6 questionnaire) 2. Asthma Quality of Life Questionnaire (AQLQ S) 3. Pre and Post bronchodilator FEV1 and FEV1/FVC 4. Absolute blood eosinophil levels (x10^9/L) and neutrophil levels (x10^9/L) 5. Percentage sputum eosinophils 6. Fractional exhaled nitric oxide levels (FeNO) 7. Percentage and total sputum neutrophils 8. Sino-nasal Outcome Test (SNOT-22) 9. EuroQOL-5D-5L Questionnaire 10. Work productivity and Activity Impairment (WPAI) Questionnaire 11. Adverse events 12. Patient treatment adherence and compliance 13. Time to first severe exacerbation and annual rate of severe exacerbation events defined by the use of systemic steroids, antibiotics or both.;Timepoint(s) of evaluation of this end point: The end point of the secondary outcome measures is 13.5 months after the participant has been registered to the T2-High or T2-Low cohort randomised controlled trial. | — |
Countries
United Kingdom
Contacts
Public ContactMirjana Sirovica
University of Leicester Clinical Trials Unit
Outcome results
None listed