Study to Assess the Efficacy and Safety of Atuliflapon in Moderate-to-Severe Uncontrolled Asthma

Asthma Clinical Trial

— FLASH  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05251259
• Other study ID #: D7552C00001
• Secondary ID: 2023-509243-27-0
• Status: Recruiting
• Phase: Phase 2
• Start date: January 27, 2022
• Est. completion date: January 29, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 randmised globally, includig particpants in Lead-in PK cohort and in Part 1 of the study.

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 based on high or low levels of biomarker at screening (Visit 1) and randomised 1:1 to Atuliflapon or placebo. An event-driven interim analysis will be performed once 30 participants with at least 1 CompEx (Composite endpoint for Exacerbations) event are observed in the group having high levels of biomarker.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 666
• Est. completion date: January 29, 2025
• Est. primary completion date: January 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 ß2-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 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) 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 ß2 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.

• 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.

• For female participants only: Currently pregnant or breast-feeding.

• 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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Atuliflapon
Randomised participants will receive Atuliflapon
• Placebo
Randomised participants will receive placebo

Locations

Country	Name	City	State
Argentina	Research Site	Bahia Blanca
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Capital Federal
Argentina	Research Site	Ciudad Capital
Argentina	Research Site	Ciudad de Buenos Aire
Argentina	Research Site	Concepción del Uruguay
Argentina	Research Site	Córdoba
Argentina	Research Site	Florencio Varela
Argentina	Research Site	Florida
Argentina	Research Site	Godoy Cruz
Argentina	Research Site	La Plata
Argentina	Research Site	Lobos
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Mendoza
Argentina	Research Site	Pilar
Argentina	Research Site	Quilmes
Argentina	Research Site	Ramos Mejía
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	Santa Fe
Australia	Research Site	Adelaide
Australia	Research Site	Clayton
Australia	Research Site	Mitcham
Australia	Research Site	South Brisbane
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Montana
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Velingrad
Bulgaria	Research Site	Vidin
Chile	Research Site	La Serena
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago de Chile
Chile	Research Site	Talca
Chile	Research Site	Temuco
Chile	Research Site	Viña del Mar
Chile	Research Site	Vitacura
Croatia	Research Site	Klenovnik
Croatia	Research Site	Petrinja
Croatia	Research Site	Rijeka
Croatia	Research Site	Split
Croatia	Research Site	Zabok
Croatia	Research Site	Zagreb
Croatia	Research Site	Zagreb
France	Research Site	Bordeaux
France	Research Site	Montpellier Cedex 5
France	Research Site	Saint-Herblain
France	Research Site	Strasbourg
France	Research Site	Toulouse
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt
Germany	Research Site	Großhansdorf
Germany	Research Site	Hamburg
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Marburg
Germany	Research Site	Schleswig
Germany	Research Site	Wiesbaden
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gödöllo
Hungary	Research Site	Gyula
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Kistarcsa
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Püspökladány
Hungary	Research Site	Szombathely
Italy	Research Site	Battipaglia (SA)
Italy	Research Site	Bergamo
Italy	Research Site	Bologna
Italy	Research Site	Ferrara
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Monza
Italy	Research Site	Napoli
Italy	Research Site	Negrar
Italy	Research Site	Reggio Emilia
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Siena
Italy	Research Site	Verona
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Gifu
Japan	Research Site	Himeji
Japan	Research Site	Kodaira-shi
Japan	Research Site	Kokubunji-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Niigata
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Setagaya-ku
Japan	Research Site	Shibuya-Ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jeonju
Korea, Republic of	Research Site	Seongnam
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Mexico	Research Site	Chihuahua
Mexico	Research Site	Chihuahua
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	León
Mexico	Research Site	Merida
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Veracruz
Mexico	Research Site	Zapopan
Netherlands	Research Site	Breda
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Groningen
Netherlands	Research Site	Zutphens
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Grudziadz
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Kielce
Poland	Research Site	Krakow
Poland	Research Site	Kraków
Poland	Research Site	Ksawerów
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Ostróda
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Tarnów
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Romania	Research Site	Baia Mare
Romania	Research Site	Brasov
Romania	Research Site	Brasov
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Caracal
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Constanta
Romania	Research Site	Deva
Romania	Research Site	Iasi
Romania	Research Site	Oradea
Romania	Research Site	Resca, Com. Dobrosloveni
Romania	Research Site	Timisoara
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Belgrade
Serbia	Research Site	Nis
Serbia	Research Site	Sremska Kamenica
Serbia	Research Site	Uzice
Serbia	Research Site	Valjevo
Slovakia	Research Site	Humenne
Slovakia	Research Site	Kezmarok
Slovakia	Research Site	Kosice
Slovakia	Research Site	Kosice
Slovakia	Research Site	Levice
Slovakia	Research Site	Presov
Slovakia	Research Site	Surany
Slovakia	Research Site	Topolcany
Slovenia	Research Site	Golnik
Slovenia	Research Site	Jesenice
Slovenia	Research Site	Kamnik
Slovenia	Research Site	Ljubljana
South Africa	Research Site	Cape Town
South Africa	Research Site	Centurion
South Africa	Research Site	Germiston
South Africa	Research Site	Johannesburg
South Africa	Research Site	Krugersdorp
South Africa	Research Site	Lenasia
South Africa	Research Site	Mount Edgecombe
South Africa	Research Site	Thohoyandou
South Africa	Research Site	Vereeniging
Spain	Research Site	A Coruña
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Benalmádena
Spain	Research Site	Jerez de la Frontera
Spain	Research Site	Laredo
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Marbella
Spain	Research Site	Mérida
Spain	Research Site	Sagunto(Valencia)
Spain	Research Site	Xàtiva
Turkey	Research Site	Ankara
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Samsun
Ukraine	Research Site	Vinnytsia
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Chorley
United Kingdom	Research Site	Corby
United Kingdom	Research Site	Cottingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Harefield
United Kingdom	Research Site	Hexham
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Reading
United Kingdom	Research Site	Watford
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Beaumont	Texas
United States	Research Site	Bellaire	Texas
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Birmingham	Alabama
United States	Research Site	Blue Ash	Ohio
United States	Research Site	Boerne	Texas
United States	Research Site	Boise	Idaho
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bronx	New York
United States	Research Site	Bronx	New York
United States	Research Site	Buckley	Michigan
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbia	South Carolina
United States	Research Site	Coral Gables	Florida
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	East Orange	New Jersey
United States	Research Site	Edmond	Oklahoma
United States	Research Site	El Paso	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Fargo	North Dakota
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fayetteville	Georgia
United States	Research Site	Fountain Valley	California
United States	Research Site	Fullerton	California
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hollywood	Florida
United States	Research Site	Horseheads	New York
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Leawood	Kansas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	McAllen	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Springs	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New Bedford	Massachusetts
United States	Research Site	Newport Beach	California
United States	Research Site	Oakwood	Ohio
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Owensboro	Kentucky
United States	Research Site	Oxon Hill	Maryland
United States	Research Site	Palmetto Bay	Florida
United States	Research Site	Pearland	Texas
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Jose	California
United States	Research Site	Savannah	Georgia
United States	Research Site	Sheffield	Alabama
United States	Research Site	Skokie	Illinois
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Sugar Land	Texas
United States	Research Site	Tallahassee	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Toledo	Ohio
United States	Research Site	Tomball	Texas
United States	Research Site	Toms River	New Jersey
United States	Research Site	Tucson	Arizona
United States	Research Site	Valhalla	New York
United States	Research Site	Vista	California
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Wylie	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Chile,  Croatia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Serbia,  Slovakia,  Slovenia,  South Africa,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to Week 12
Secondary	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.	Baseline up to Week 12
Secondary	Time to first CompEx Asthma event (Composite endpoint for Exacerbations)	The clinical efficacy of Atuliflapon Dose A will be assessed by calculating 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.	Baseline up to Week 12
Secondary	Change from baseline in Pre-bronchodilator forced expiratory volume in 1 second	The clinical efficacy of Atuliflapon will be evaluated in comparison to placebo (based on biomarker) of adult participants with moderate-to-severe uncontrolled asthma.	Baseline, Week 4 and Week 12
Secondary	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.	Baseline, Week 4 and Week 12
Secondary	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.	Baseline Week 4, Week 8, Week 12
Secondary	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.	Baseline Week 4, Week 8, Week 12
Secondary	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.	Baseline Week 4, Week 8, Week 12
Secondary	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.	Baseline up to Week 12
Secondary	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.	Baseline up to Week 12
Secondary	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.	Day 1 and Day 15
Secondary	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.	Day 1 and Day 15
Secondary	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.	Day 15
Secondary	Part 1 Cohort: Atuliflapon plasma concentrations in all participants, pre-dose samples	To pre-dose plasma concentrations of Atuliflapon will be summarised.	Baseline, Week 4 and Week 12
Secondary	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.	Baseline up to Week 12