Last updated 12 days ago
Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
666 patients around the world
Available in Mexico, Argentina, Chile
The study will enroll participants with moderate to severe uncontrolled asthma who are on
low-dose inhaled corticosteroid (ICS) - a long-acting beta-agonist (LABA) or
medium-to-high-dose ICS with or without LABA background treatment.
The study will be initiated by Lead-in pharmacokinetics (PK) cohort in asthma
participants. Participant will be randomised globally, including participants in Lead-in
PK cohort (2 arms) and in Part 1 of the study (2 arms).
In the Lead-in PK cohort, participants will be randomised to Atuliflapon or placebo
(recruitment completed).
In Part 1 of the study, participants will be stratified by geographical region, and
grouped based on high or low levels of biomarker at screening (Visit 1).
AstraZeneca
1Research sites
666Patients around the world
This study is for people with
Asthma
Requirements for the patient
To 80 Years
All Gender
Medical requirements
- Lead-in PK Cohort: 18 to 55 years of age inclusive at the time of signing the informed consent at screening Visit 1.Lead-in PK Cohort: Bodyweight 50 to 120 kg inclusive and BMI 18 to 32 kg/m^2 inclusive at screening Visit 1.Lead-in PK Cohort: Documented asthma diagnosis ≥12 months prior to screening Visit 1.Lead-in PK Cohort: Able to perform acceptable lung function testing for FEV1 according to American Thoracic Society / European Respiratory Society ATS/ERS 2019 acceptability criteria.Lead-in PK Cohort: Morning pre-bronchodilator BD forced expiratory volume FEV1 ≥ 40% predicted at screening Visit 1 and Visit 2.Lead-in PK Cohort: Treated with low dose inhaled corticosteroid plus long-acting β2-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.Lead-in PK Cohort: 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 and body mass index BMI < 35 kg/m^2.General Inclusion Criteria for Part 1: Documented history of ≥ 1 severe asthma exacerbation within 1 year prior to screening Visit 1.General Inclusion Criteria for Part 1: Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.General Inclusion Criteria for Part 1: Morning pre-BD FEV1 between ≥ 40% and ≤ 85% predicted at screening Visit 1 and Visit 3.General Inclusion Criteria for Part 1: An Asthma Control Questionnaire ACQ-6 score ≥ 1.5 at screening Visit 1 and at Visit 3.
- A severe asthma exacerbation within 8 weeks of screening visit 1 or within 12 weeks of randomisation Visit 3.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.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 × 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 IM before randomization 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 β2 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 Visit 1.Treatment with simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to screening Visit 1.Treatment with sensitive cytochrome 3A substrates with narrow therapeutic window should be avoided from randomization to study drug.For female participants on ethinyl oestradiol containing combined oral contraceptives, the ethinyl oestradiol doses exceeding 20 mcg per day.Concurrent enrolment in another clinical study.Previous participation in the current clinical study.Participant treated with any investigational drug within 4 months prior to screening Visit 1.Known history of allergy or reaction to any component of the study intervention formulation.Smokers with smoking history of < 10 pack-years or users of vaping or e-cigarettes, must have stopped at least 6 months prior to screening Visit 1.Involvement in the planning and/or conduct of the study.Donation of blood ≥ 450 mL within 3 months or donation of plasma within 14 days before screening Visit 1.Major surgery within 8 weeks prior to screening Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during the screening Visit 1, treatment or follow-up periods.
Sites
Centro Integral de Medicina Respiratoria (CIMER) - Tucumán
Recruiting
StudyFLASH
SponsorAstraZeneca
Study typeInterventional
Conditions
Asthma
Requirements
To 80 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT05251259
