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

JRCT ID: jRCT2031210680

Registered date:18/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Asthma
• Date of first enrollment: 27/04/2022
• Target sample size: 666
• Countries of recruitment: Argentina,Japan,Australia,Japan,Bulgaria,Japan,Chile,Japan,Croatia,Japan,France,Japan,Germany,Japan,Hungary,Japan,Italy,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Romania,Japan,Serbia,Japan,Slovakia,Japan,Slovenia,Japan,South Africa,Japan,South Korea,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan,United States of America,Japan
• Study type: Interventional

Intervention(s)

Drug: Atuliflapon
Randomized participants will receive Atuliflapon

Drug: Placebo
Randomized participants will receive placebo

Outcome(s)

Primary Outcome

Time to first CompEx Asthma event (Composite endpoint for Exacerbations)
[ 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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 or more 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)140% or more predicted at screening Visit 1 and Visit 2.

- Treated with low dose inhaled corticosteroid plus long-acting Beta 2-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 or more 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 or more and body mass index (BMI) < 35 kg/m^2.

- Documented history of 1 or more 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% or more and 85% or less predicted at screening screening Visit 1 and Visit 3.

- An Asthma Control Questionnaire (ACQ)-6 score1.5 or more at screening screening Visit 1 and at Visit 3.

Exclude criteria

- A severe asthma exacerbation within 8 weeks of Screening (Visit 1) or within 12 weeks of randomisation (Visit 3).

- A severe asthma exacerbation within 8 weeks of Screening (Visit 1) or within 12 weeks of randomisation (Visit 3).

- 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 x 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 (intramuscular) before randomisation (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 Beta2 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.

Related Information

• Primary Sponsor: Ageishi Yuji
• Secondary ID(s): NCT05251259