Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
- Conditions
- Asthma
- Registration Number
- JPRN-jRCT2031210680
- Lead Sponsor
- Ageishi Yuji
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 1102
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 and Part 2:
- 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 years 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.
- A severe asthma exacerbation within 8 weeks of screening visit 1.
- A positive test result of an approved antigen test (confirmed by a positive RT-PCR test) or a positive RT-PCR test for SARS-CoV-2, the virus responsible for COVID-19, at screening Visit 1 or at Visit 2 for the PK Lead-in cohort. For Part 1 and Part 2 the testing will be done at Visit 3. Results from the mandatory tests at Visit 2 (PK Lead-in cohort) and Visit 3 (Part 1, Part 2) must not be older than 48 hours and must be available before randomisation.
- 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 or untreated latent tuberculosis (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.
- 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 Beta 2 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 st
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method