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Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
CompletedPhase 2
Sponsor: AstraZeneca
Conditions: Asthma
Interventions: Atuliflapon, Placebo
Countries: United States, Argentina, Australia, Bulgaria, Chile, Croatia, Germany, Hungary
This is a randomised, placebo-controlled, double-blind study to assess the efficacy and safety of Atuliflapon administered once daily over a 12-week treatment period to adult participants with moderate to severe uncontrolled asthma.
Eligibility overview
Sex: ALL
Age: 18 Years to 80 Years
Healthy volunteers: No
Study type: INTERVENTIONAL
Eligibility 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 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)1 ≥ 40% predicted at screening Visit 1 and Visit 2. * 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. Also, treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 3 months 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 and body mass index (BMI) \< 35 kg/m\^2. * Documented history of ≥ 1 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% and ≤ 85% predicted at screening Visit 1 and Visit 3. * An Asthma Control Questionnaire (ACQ)-6 score ≥ 1.5 at screening Visit 1 and at Visit 3. Exclusion Criteria * 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. For Part 1 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) 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 × 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.
Locations (234)
- Birmingham, Alabama, United States
- Sheffield, Alabama, United States
- Phoenix, Arizona, United States
- Tucson, Arizona, United States
- Little Rock, Arkansas, United States
- Bakersfield, California, United States
- Fountain Valley, California, United States
- Huntington Beach, California, United States
- Los Angeles, California, United States
- Newport Beach, California, United States
- San Jose, California, United States
- Valencia, California, United States
- Colorado Springs, Colorado, United States
- Cutler Bay, Florida, United States
- Cutler Bay, Florida, United States
- Hialeah, Florida, United States
- Hialeah, Florida, United States
- Hialeah, Florida, United States
- Miami, Florida, United States
- Miami, Florida, United States
- Miami, Florida, United States
- Miami, Florida, United States
- Orlando, Florida, United States
- Tampa, Florida, United States
- Tampa, Florida, United States
- Fayetteville, Georgia, United States
- Lithonia, Georgia, United States
- Savannah, Georgia, United States
- Boise, Idaho, United States
- Lexington, Kentucky, United States
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