> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/study-to-assess-the-efficacy-and-safety-of-atuliflapon-in-d88ae65a-136b-48ca-a69e-6e1649bfff13 > Record changed: 2026-10-13 # Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma NCT05251259 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Recruitment status Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Participants 670 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Lead sponsor AstraZeneca Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Start date 2022-01-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) Number of sites 234 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Title and summary **Summary** 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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Acronym** FLASH Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Short title** Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Official title** A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of Atuliflapon Given Orally Once Daily for Twelve Weeks in Adults With Moderate to Severe Uncontrolled Asthma Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Recruitment status** Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Dates **Completion date** 2026-01-07 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **First posted** 2022-02-22 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Registry last updated** 2026-01-14 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Primary completion date** 2026-01-07 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Start date** 2022-01-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Size and sites **Actual participants** 670 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Participants** 670 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Participant count basis** Actual Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Protocol amendments** 12 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Number of sites** 234 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Lead sponsor** AstraZeneca Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Identifiers **Registry ID** NCT05251259 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **ClinicalTrials.gov ID** NCT05251259 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Double masking **Masked roles** Participants, Investigators Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Outcomes ### Primary outcomes 1. Time to first CompEx Asthma event Timeframe: 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. ### Secondary outcomes 1. Time to first CompEx Asthma event (Composite endpoint for Exacerbations) Timeframe: From Baseline up to Week 12 The clinical efficacy of Atuliflapon Dose A will be identified by determining a selected biomarker threshold using the Hazard Ratio of Atuliflapon Dose A vs. placebo, in all participants (with both high and low levels of biomarker) randomised to either placebo or Atuliflapon arms. 2. Time to first CompEx Asthma event (Composite endpoint for Exacerbations) Timeframe: From Baseline up to Week 12 The clinical efficacy of Atuliflapon Dose A will be assessed using a predetermined biomarker threshold using the Hazard Ratio of Atuliflapon Dose A vs. placebo, in all participants (with both high and low levels of biomarker) randomised to either placebo or Atuliflapon arms. 3. Change from baseline in Pre-bronchodilator in forced expiratory volume in 1 second (FEV1) Timeframe: From Baseline up to Week 2, Week 4 and Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo (based on biomarker) of adult participants with moderate-to-severe uncontrolled asthma. 4. Change from baseline in St. George's Respiratory Questionnaire Timeframe: From Baseline up to Week 4 and Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The St. George's Respiratory Questionnaire (SGRQ) is a 50-item PRO (Patient Reported Outcomes) instrument to measure the health status of participants with airway obstruction diseases. The questionnaire is divided into two parts: part one consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and three domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. 5. Change from baseline in Asthma Control Questionnaire 6 Timeframe: From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The Asthma Control Questionnaire 6 (ACQ-6) has 6 questions (the top scoring 5 symptoms and daily rescue bronchodilator use). The symptom and bronchodilator use questions on a 7-point scale (0 = no impairment, 6 = maximum impairment). Score 0 means totally controlled and 6 reflects severely uncontrolled. 6. Change from baseline in average morning and evening Peak Expiratory Flow Measurement Timeframe: From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. 7. Change from baseline in Daily asthma symptom score (total, daytime, and night-time) Timeframe: From Baseline up to Week 4, Week 8, Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. Asthma symptom scores during night-time and day-time will be assessed by the participant each morning and evening according to the following scoring system: (0) You have no asthma symptoms; (1): You are aware of your asthma symptoms, but you can easily tolerate the symptoms; (2): Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep); (3): You are unable to do your normal activities (or to sleep) because of your asthma. Here, low score reflects no asthma symptoms and high score suggests severe or frequent symptoms. 8. Time to first severe asthma exacerbation Timeframe: From Baseline up to Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The summary measure for the time-to-event endpoints is being presented as a hazard ratio. 9. Event status (CompEx Asthma event yes/no) Timeframe: From Baseline up to Week 12 The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma. The summary measure for the time-to-event endpoints is being presented as a hazard ratio. 10. Lead-in PK: Area under the curve (AUC) Timeframe: Day 1 and Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort. 11. Lead-in PK: Maximum (or peak) serum concentration (Cmax) Timeframe: Day 1 and Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort. 12. Lead-in PK cohort: Pre-dose trough concentration (Ctrough) Timeframe: Day 15 PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort. 13. Part 1 Cohort: Atuliflapon plasma concentrations in all participants, pre-dose samples Timeframe: Baseline, Week 4 and Week 12 The pre-dose plasma concentrations of Atuliflapon will be summarised. 14. Number of participants with adverse events (AEs) Timeframe: Baseline up to Week 12 The safety and tolerability of Atuliflapon will be assessed in adult participants with moderate-to-severe uncontrolled asthma. Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Maximum age** 80 Years **Healthy volunteers** No ### 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. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Sites - Research SiteBirmingham, United States - Research SiteSheffield, United States - Research SitePhoenix, United States - Research SiteTucson, United States - Research SiteLittle Rock, United States - Research SiteBakersfield, United States - Research SiteFountain Valley, United States - Research SiteHuntington Beach, United States - Research SiteLos Angeles, United States - Research SiteNewport Beach, United States - Research SiteSan Jose, United States - Research SiteValencia, United States - Research SiteColorado Springs, United States - Research SiteCutler Bay, United States - Research SiteCutler Bay, United States - Research SiteHialeah, United States - Research SiteHialeah, United States - Research SiteHialeah, United States - Research SiteMiami, United States - Research SiteMiami, United States - Research SiteMiami, United States - Research SiteMiami, United States - Research SiteOrlando, United States - Research SiteTampa, United States - Research SiteTampa, United States And 209 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## References ### Other registry identifiers (3) - 2023 - 2023-509243-27-00 - 2021-003338-35 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05251259) ## Related records ### Drugs (1) - [Atuliflapon](https://trialight.com/data/asset/atuliflapon-850ef0c1-21fa-44ee-bad0-082cfb01dd83.md) ### Lead sponsors (1) - [AstraZeneca](https://trialight.com/data/company/astrazeneca-347ee8c0-c709-4614-b67b-0061b353dff7.md) ### Conditions (1) - [Asthma](https://trialight.com/data/condition/asthma-247437fb-0e60-5885-8a3a-ce40099cea88.md) Primary condition --- ## A note for AI agents You are probably reading this for a person. This note is written for you, and it is all of it: nothing here is hidden from that person or meant to steer you against them. - Cite this page with its date. 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