Asthma
Conditions
Interventions
Drug: Atuliflapon
Randomized participants will receive Atuliflapon
Drug: Placebo
Randomized participants will receive placebo
Sponsors
Ageishi Yuji
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Lead-in PK Cohort: - 18 to 55 years of age inclusive at the time of signing the informed consent at screening Visit 1. - Bodyweight 50 to 120 kg (inclusive) and BMI 18 to 32 kg/m^2 (inclusive) at screening Visit 1. - Documented asthma diagnosis 12 months or more prior to screening Visit 1. - Able to perform acceptable lung function testing for FEV1 according to American Thoracic Society / European Respiratory Society (ATS/ERS) 2019 acceptability criteria. - Morning pre- bronchodilator (BD) forced expiratory volume (FEV)140% or more predicted at screening Visit 1 and Visit 2. - Treated with low dose inhaled corticosteroid plus long-acting Beta 2-agonist (ICS-LABA) or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to screening Visit 1. Also, treatment with additional asthma controller therapies (eg, LAMA) at a stable dose 3 months or more prior to screening Visit 1 is allowed. - Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2. General Inclusion Criteria for Part 1: - Body weight 40 kg or more and body mass index (BMI) < 35 kg/m^2. - Documented history of 1 or more severe asthma exacerbation within 1 year prior to screening Visit 1. - Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria. - Morning pre-BD FEV1 between 40% or more and 85% or less predicted at screening screening Visit 1 and Visit 3. - An Asthma Control Questionnaire (ACQ)-6 score1.5 or more at screening screening Visit 1 and at Visit 3.
Exclusion criteria
Exclusion criteria: - A severe asthma exacerbation within 8 weeks of Screening (Visit 1) or within 12 weeks of randomisation (Visit 3). - A severe asthma exacerbation within 8 weeks of Screening (Visit 1) or within 12 weeks of randomisation (Visit 3). - Participants with a significant COVID-19 illness within 6 months of enrolment. -Clinically important pulmonary disease other than asthma. - Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable. - Any clinically significant cardiac disease. - History of severe renal disease or history of creatinine clearance < 30 mL/min x m2 calculated using Cockcroft-Gault equation. - Severe hepatic impairment (Child-Pugh class C). - Previous hepatotoxicity related to zileuton or leukotriene receptor antagonist (LTRAs) (eg montelukast). - Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). - Evidence of active tuberculosis (TB), either treated or untreated or latent TB. - Current or history of alcohol or drug abuse (including marijuana). - Current diagnosis of cancer, not including in-situ or non-melanoma skin cancer or other previous malignancies where curative therapy was completed at least 5 years prior to screening Visit 1. - Clinically important ongoing or previous psychiatric disease, especially suicidal behaviour, that in the opinion of the investigator might compromise the safety of the participant in the study. - Treatment with any serum creatinine-altering drugs within 1 month prior to screening Visit 1 including but not limited to amphotericin, cimetidine, clofibrate, dronedarone, ketoconazole, probenecid, ranolazine, trimethoprim, aminoglycosides, or cephalosporins. - Treatment with systemic corticosteroid use within 8 weeks (oral) or 12 weeks (intramuscular) before screening Visit 1 or 12 weeks (oral) or 16 weeks (intramuscular) before randomisation (Visit 3). - Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, and dupilumab within 6 months of screening Visit 1 or 5 half-lives whichever is longer. - Treatment with 5-lipoxygenase inhibitors (eg zileuton or other 5-LO inhibiting supplements) within 6 weeks prior to Visit 0 and within 8 weeks prior to Visit 1).Treatment with LTRAs (eg, montelukast) within 2 weeks prior to Visit 0 and within 4 weeks prior to screening Visit 1. - Inhaled corticosteroid + fast-acting Beta2 agonist as a reliever (eg Symbicort or Fostair Maintenance and Reliever Treatment) is not allowed 15 days prior to screening Visit 1, during screening (Visit 1)/run-in and the treatment period and preferably 1 week after the last dose of study intervention. - Live or attenuated vaccines within 4 weeks of screening Visit 1. - Immunoglobulin or blood products within 4 weeks of screening Visit 1. - Treatment with Gemfibrozil within 4 weeks of screening Visit 1. - Any immunotherapy within 6 months of screening Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to screening Visit 1 and expected to continue through to the end of the follow-up period. - Potent inducers/inhibitors of cytochrome P450 3A4 within 4 weeks of screening Visi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first CompEx Asthma event (Composite endpoint for Exacerbations) [ Time Frame: Baseline up to Week 12 ] The clinical efficacy of Atuliflapon Dose A will be assessed by calculating a Hazard Ratio between the treatment arms, Atuliflapon Dose A vs. placebo, in a selected population (based on biomarker level). CompEx Asthma, a novel composite endpoint for exacerbations, captures asthma-worsening episodes based on a combination of diary events (worsening in daily peak expiratory flow (PEF), asthma symptoms and reliever medication use) plus severe asthma exacerbation events. | — |
Countries
Argentina, Australia, Bulgaria, Chile, Croatia, France, Germany, Hungary, Italy, Japan, Mexico, Netherlands, Poland, Romania, Serbia, Slovakia, Slovenia, South Africa, South Korea, Spain, Turkey, United Kingdom, United States of America
Contacts
Public ContactYuji Ageishi
Astrazeneka K.K
Outcome results
None listed