AsthmaPhase 2FLASHNCT05251259
Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma
A Phase 2 study testing Atuliflapon in people with Asthma, run by AstraZeneca at 234 sites in 20 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma
- What is being tested?
- Atuliflapon
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 670 participants
- Where
- 234 sitesin 20 countries
- Study dates
- 27 Jan 2022to 7 Jan 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
234 sites in 20 countries.
234 sites in 20 countries
United States64 sites
Research Site
Ann Arbor, Michigan, 48105
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Austin, Texas, 78705
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Bakersfield, California, 93301
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Beaumont, Texas, 77701
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Bellaire, Texas, 77401
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Birmingham, Alabama, 35211
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Blue Ash, Ohio, 45242
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Boise, Idaho, 83706
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Charlotte, North Carolina, 28210
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Charlotte, North Carolina, 28287
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Colorado Springs, Colorado, 80907
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Columbia, South Carolina, 29204
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Cutler Bay, Florida, 33157
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Cutler Bay, Florida, 33189
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Dallas, Texas, 75225
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Dayton, Ohio, 45439
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East Orange, New Jersey, 07018
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Edmond, Oklahoma, 73034
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El Paso, Texas, 79902
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El Paso, Texas, 79903
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Farmington Hills, Michigan, 48336
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Fayetteville, Georgia, 30214
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Fountain Valley, California, 92708
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Gastonia, North Carolina, 28054
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Greenville, South Carolina, 29615
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Hialeah, Florida, 33012
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Hialeah, Florida, 33015
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Hialeah, Florida, 33016
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Houston, Texas, 77022
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Huntington Beach, California, 92647
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Lexington, Kentucky, 40509
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Lithonia, Georgia, 30038
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Little Rock, Arkansas, 72212
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Los Angeles, California, 90025
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McKinney, Texas, 75069
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Miami, Florida, 33125
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Miami, Florida, 33155
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Miami, Florida, 33173
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Miami, Florida, 33174
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Milwaukee, Wisconsin, 53228
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New Bedford, Massachusetts, 02740
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Newport Beach, California, 92663
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Orlando, Florida, 32807
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Owensboro, Kentucky, 42301
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Oxon Hill, Maryland, 20745
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Phoenix, Arizona, 85020
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Pittsburgh, Pennsylvania, 15241
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Saint Charles, Missouri, 63301
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San Antonio, Texas, 78258
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San Jose, California, 95117
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Savannah, Georgia, 31406
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Sheffield, Alabama, 35660
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Spartanburg, South Carolina, 29303
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St Louis, Missouri, 63141
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Sugar Land, Texas, 77479
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Tampa, Florida, 33613
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Tampa, Florida, 33615
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The Bronx, New York, 10459
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Tomball, Texas, 77375
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Toms River, New Jersey, 08755
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Tucson, Arizona, 85741
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Valencia, California, 91355
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Valhalla, New York, 10595
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Wilmington, North Carolina, 28401
Japan27 sites
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Bunkyō City, 113-8510
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Chūōku, 103-0022
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Chūōku, 104-0031
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Fukuoka, 811-1351
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Fukuoka, 815-8588
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Fukuoka, 819-8555
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Himeji, 672-8064
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Kawachinagano-shi, 586-8521
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Kobe, 653-0013
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Kodaira-shi, 187-0024
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Koga-shi, 811-3195
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Kokubunji-shi, 185-0014
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Kyoto, 601-8213
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Nakagun, 259-0114
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Niigata, 940-0840
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Osaka, 530-0001
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Osaka, 531-0073
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Sagamihara-shi, 252-0315
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Sapporo, 064-0801
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Setagaya-ku, 157-0072
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Shibuya-Ku, 150-0013
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Tokyo, 157-0066
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Tokyo, 160-0017
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Toshima-ku, 170-0002
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Toshima-ku, 170-0003
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Yokohama, 223-0059
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Yokohama, 231-8682
Argentina26 sites
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Bahía Blanca, 8000
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Buenos Aires, C1121ABE
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Buenos Aires, C1414AIF
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CABA, 1008
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Capital Federal, C1122AAK
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Ciudad Capital, 5500
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Ciudad de Buenos Aire, C1425BEN
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Concepción del Uruguay, 3260
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Córdoba, X5003DCE
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Florida, B1602DQD
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Godoy Cruz, M5501ARP
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La Plata, B1900
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La Plata, B1902COS
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Lobos, 7240
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Mar del Plata, 7600
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Mar del Plata, B7600
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Mendoza, 5500
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Mendoza, 5501
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Mendoza, M5500CCG
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Pilar, B1629AHJ
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Quilmes, B1878FNR
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Ramos Mejía, B1704ETD
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Rosario, 2000
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San Juan Bautista, 1888
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San Miguel de Tucumán, 4000
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Santa Fe, 3000
United Kingdom19 sites
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Birmingham, B15 2SQ
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Bradford, BD9 6RJ
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Cardiff, CF15 9SS
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Chorley, PR7 7NA
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Corby, NN17 2UR
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Cottingham, HU16 5JQ
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Glasgow, ML4 3NJ
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Harefield, UB9 6JH
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Hexham, NE46 1QJ
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Leeds, LS9 7TF
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Leicester, LE3 9QP
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Liverpool, L22 0LG
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Liverpool, L7 8XP
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London, SW10 9NH
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London, W1T 6AH
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London, W2 1NY
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Manchester, M15 6SE
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Portsmouth, PO6 3LY
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Reading, RG1 5AN
Poland17 sites
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Bialystok, 15-044
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Gdansk, 80-382
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Grudziądz, 86-300
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Katowice, 40-282
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Katowice, 40-611
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Kielce, 25-751
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Krakow, 31-455
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Krakow, 31-513
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Ksawerów, 95-054
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Lodz, 90-127
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Lodz, 90-153
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Lodz, 90-302
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Ostróda, 14-100
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Poznan, 60-702
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Tarnów, 33-100
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Wroclaw, 50-381
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Wroclaw, 53-301
Romania13 sites
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Brasov, 500091
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Brasov, 500112
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Brasov, 500283
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Bucharest, 010626
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Bucharest, 014461
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Bucharest, 020125
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Bucharest, 061696
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Caracal, 235200
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Cluj-Napoca, 400371
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Deva, 330084
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Iași, 700115
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Resca, Com. Dobrosloveni, 237143
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Timișoara, 300310
Bulgaria11 sites
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Kozloduy, 3320
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Montana, 3400
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Plovdiv, 4000
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Rousse, 7000
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Sliven, 8800
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Sofia, 1113
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Sofia, 1202
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Sofia, 1407
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Stara Zagora, 6003
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Velingrad, 4691
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Vidin, 3700
Chile8 sites
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Quillota, 2260000
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Santiago, 7500698
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Santiago, 7530234
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Santiago, 8330336
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Talca, 3481349
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Temuco, 4802815
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Viña del Mar, 2531172
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Vitacura, 7630226
Spain8 sites
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Badalona, 08916
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Barcelona, 08017
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Benalmádena, 29631
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Jerez de la Frontera, 11407
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Laredo, 39770
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Madrid, 28007
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Madrid, 28031
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Málaga, 29010
South Korea6 sites
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Incheon, 405-760
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Jeonju, 54907
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Seoul, 02841
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Seoul, 06591
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Seoul, 138-736
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Suwon, 16499
Croatia5 sites
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Klenovnik, 42244
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Petrinja, 44250
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Rijeka, 51000
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Split, 21000
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Zagreb, 10 000
Germany5 sites
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Berlin, 12159
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Frankfurt, 60313
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Leipzig, 04103
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Lübeck, 23552
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Marburg, 35037
Hungary5 sites
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Gödöllő, 2100
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Gyula, 5700
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Hajdúnánás, 4080
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Pécs, 7635
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Szombathely, 9700
Serbia4 sites
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Belgrade, 11000
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Belgrade, 11070
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Užice, 31000
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Valjevo, 14000
Ukraine4 sites
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Chernivtsі, 58002
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Ivano-Frankivsk, 76000
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Kyiv, 01135
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Vinnytsia, 21029
Netherlands3 sites
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Breda, 4818 CK
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Eindhoven, 5623 EJ
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Groningen, 9713 GZ
Slovakia3 sites
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Levice, 934 01
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Prešov, 08001
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Topoľčany, 95501
South Africa3 sites
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Germiston, 1401
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Krugersdorp, 1740
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Lenasia, 1827
About this study
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
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.
Read the detailed description
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).
- Conditions
- Asthma
- Being tested
- Atuliflapon, Placebo
- Keywords
- Efficacy, Safety, Multiple Dose Levels, Adults
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtuliflaponDrug
Also called AZD5718
Randomised participants will receive Atuliflapon
PlaceboDrug
Randomised participants will receive matching placebo to Atuliflapon.
| Study group | Role | What they receive |
|---|---|---|
| Lead-in PK cohort (Atuliflapon) | Experimental | Randomised participants will receive Atuliflapon in Lead-in PK period of the study. Receives: Drug: Atuliflapon |
| Lead-in PK cohort (Placebo) | Placebo comparator | Randomised participants will receive matching placebo to Atuliflapon in Lead-in PK cohort of the study. Receives: Drug: Placebo |
| Part 1 (Atuliflapon) | Experimental | Randomised participants will receive Atuliflapon in Part 1 of the study. Receives: Drug: Atuliflapon |
| Part 1 (Placebo) | Placebo comparator | Randomised participants will receive matching placebo to Atuliflapon in Part 1 of the study. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first CompEx Asthma event
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.
Measured: Baseline up to Week 12
Secondary outcomes (14)
Time to first CompEx Asthma event (Composite endpoint for Exacerbations)
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.
Measured: From Baseline up to Week 12
Time to first CompEx Asthma event (Composite endpoint for Exacerbations)
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.
Measured: From Baseline up to Week 12
Change from baseline in Pre-bronchodilator in forced expiratory volume in 1 second (FEV1)
The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo (based on biomarker) of adult participants with moderate-to-severe uncontrolled asthma.
Measured: From Baseline up to Week 2, Week 4 and Week 12
Change from baseline in St. George's Respiratory Questionnaire
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.
Measured: From Baseline up to Week 4 and Week 12
Change from baseline in Asthma Control Questionnaire 6
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.
Measured: From Baseline up to Week 4, Week 8, Week 12
Change from baseline in average morning and evening Peak Expiratory Flow Measurement
The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo in adult participants with moderate-to-severe uncontrolled asthma.
Measured: From Baseline up to Week 4, Week 8, Week 12
Change from baseline in Daily asthma symptom score (total, daytime, and night-time)
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.
Measured: From Baseline up to Week 4, Week 8, Week 12
Time to first severe asthma exacerbation
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.
Measured: From Baseline up to Week 12
Event status (CompEx Asthma event yes/no)
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.
Measured: From Baseline up to Week 12
Lead-in PK: Area under the curve (AUC)
PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Measured: Day 1 and Day 15
Lead-in PK: Maximum (or peak) serum concentration (Cmax)
PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Measured: Day 1 and Day 15
Lead-in PK cohort: Pre-dose trough concentration (Ctrough)
PK parameter of Atuliflapon will be assessed. Participants will be randomised to Atuliflapon Dose A in the Lead-in PK Cohort.
Measured: Day 15
Part 1 Cohort: Atuliflapon plasma concentrations in all participants, pre-dose samples
The pre-dose plasma concentrations of Atuliflapon will be summarised.
Measured: Baseline, Week 4 and Week 12
Number of participants with adverse events (AEs)
The safety and tolerability of Atuliflapon will be assessed in adult participants with moderate-to-severe uncontrolled asthma.
Measured: Baseline up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2022
- Study start27 Jan 2022
- Primary completion7 Jan 2026
- Study completion7 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 670 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05251259
- Sponsor's protocol ID
- D7552C00001
- Other IDs
- 2023-509243-27-00, 2021-003338-35, 2023
- Acronym
- FLASH
- Status last verified
- Jan 2026
- First submitted
- 20 Dec 2021
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05251259
- Acronym / sponsor ID
- FLASH / D7552C00001
- Conditions
- Asthma
- Keywords
- Efficacy, Safety, Multiple Dose Levels, Adults
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 670 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- 7 Jan 2026 (actual)
- Study completion
- 7 Jan 2026 (actual)
- First posted
- 22 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lead-in PK cohort (Atuliflapon) | Experimental | Drug: AtuliflaponRandomised participants will receive Atuliflapon in Lead-in PK period of the study. |
| Lead-in PK cohort (Placebo) | Placebo comparator | Drug: PlaceboRandomised participants will receive matching placebo to Atuliflapon in Lead-in PK cohort of the study. |
| Part 1 (Atuliflapon) | Experimental | Drug: AtuliflaponRandomised participants will receive Atuliflapon in Part 1 of the study. |
| Part 1 (Placebo) | Placebo comparator | Drug: PlaceboRandomised participants will receive matching placebo to Atuliflapon in Part 1 of the study. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (34 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtuliflaponAlso: AZD5718Randomised participants will receive Atuliflapon | Drug | Lead-in PK cohort (Atuliflapon), Part 1 (Atuliflapon) |
| PlaceboRandomised participants will receive matching placebo to Atuliflapon. | Drug | Lead-in PK cohort (Placebo), Part 1 (Placebo) |
Primary outcome
Time to first CompEx Asthma event
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.
14 secondary outcomes
Time to first CompEx Asthma event (Composite endpoint for Exacerbations)
Time frame: From Baseline up to Week 12
Time to first CompEx Asthma event (Composite endpoint for Exacerbations)
Time frame: From Baseline up to Week 12
Change from baseline in Pre-bronchodilator in forced expiratory volume in 1 second (FEV1)
Time frame: From Baseline up to Week 2, Week 4 and Week 12
Change from baseline in St. George's Respiratory Questionnaire
Time frame: From Baseline up to Week 4 and Week 12
Change from baseline in Asthma Control Questionnaire 6
Time frame: From Baseline up to Week 4, Week 8, Week 12
Change from baseline in average morning and evening Peak Expiratory Flow Measurement
Time frame: From Baseline up to Week 4, Week 8, Week 12
Change from baseline in Daily asthma symptom score (total, daytime, and night-time)
Time frame: From Baseline up to Week 4, Week 8, Week 12
Time to first severe asthma exacerbation
Time frame: From Baseline up to Week 12
Event status (CompEx Asthma event yes/no)
Time frame: From Baseline up to Week 12
Lead-in PK: Area under the curve (AUC)
Time frame: Day 1 and Day 15
Lead-in PK: Maximum (or peak) serum concentration (Cmax)
Time frame: Day 1 and Day 15
Lead-in PK cohort: Pre-dose trough concentration (Ctrough)
Time frame: Day 15
Part 1 Cohort: Atuliflapon plasma concentrations in all participants, pre-dose samples
Time frame: Baseline, Week 4 and Week 12
Number of participants with adverse events (AEs)
Time frame: Baseline up to Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
234 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atuliflapon in people with Asthma, run by AstraZeneca at 234 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 234 sites in United States, Japan, Argentina, United Kingdom, Poland and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first CompEx Asthma event (time frame: Baseline up to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.