Study to Assess the Efficacy and Safety of AZD5718 in Moderate-to-Severe Uncontrolled Asthma

• Status: Recruiting
• Trial end date: 2024-02-09
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomised, placebo-controlled, double-blind study with an active comparator (montelukast) arm to assess the efficacy and safety of AZD5718 administered at multiple dose levels over a 12-week treatment period to adult participants with moderate-to-severe uncontrolled asthma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Montelukast

Criteria

Inclusion Criteria

Lead-in PK Cohort:

• 18 to 55 years of age inclusive at the time of signing the informed consent at Visit 1.

• Bodyweight 50 to 100 kg (inclusive) and BMI 18 to 30 kg/m^2 (inclusive) at Visit 1.

• Documented asthma diagnosis ≥ 12 months prior to 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 ≥ 70% predicted at 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 Visit 1. Also, treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 3 months prior to Visit 1 is allowed.

• Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2.

Part 1 and Part 2: Specific Inclusion Criteria for Pre-Screening:

• Participant must be 18 to 80 years of age inclusive at the time of signing the informed consent

• Treated with low dose ICS-LABA or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to Visit 1.

• Documented history of ≥ 1 severe asthma exacerbation within 12 months prior to Visit 0.

• Morning pre-BD FEV1 between ≥ 40% and ≤ 80% predicted at Visit 0.

• Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.

Specific Biomarker Inclusion Criteria for Part 1:

• Test for prospective biomarkers will be performed at visit 0 or 1.

General Inclusion Criteria for Part 1 and Part 2:

• Body weight ≥ 40 kg and body mass index (BMI) < 35 kg/m^2.

• Documented physician-diagnosed asthma ≥ 12 months prior to 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 ≤ 80% predicted at Visit 1 and at Visit 3.

• An Asthma Control Questionnaire (ACQ)-6 score ≥ 1.5 at Visit 1 and at Visit 3.

• Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2.

Additional Specific Criteria for Visit 3 (randomisation):

• Pre-bronchodilator FEV1 between ≥ 40% and ≤ 80% predicted.

• ACQ-6 score of ≥ 1.5.

• At least 70% compliance with usual asthma background medication during run-in period (from Visit 2 to Visit 3) based on the daily asthma electronic patient-reported outcome (ePROs).

Exclusion Criteria

• A severe asthma exacerbation within 8 weeks of randomisation.

• A positive nucleic acid test (eg Real Time-Polymerase Chain Reaction) at Visit 1 or at Visit 3 for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for Coronavirus disease 2019 (COVID-19).

• Participants with a significant COVID-19 illness within 6 months of enrolment.

• Clinically important pulmonary disease other than asthma.

• Galactose intolerance, Lapp lactase deficiency, or glucose-galactose metabolism.

• 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 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).

• History of or current 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 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 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 Visit 1.

• Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, and dupilumab within 6 months of Visit 1 or 5 half-lives whichever is longer.

• Treatment with leukotriene receptor antagonist (LTRAs) or 5-lipoxygenase inhibitors (eg zileuton and montelukast; at least 8 weeks prior to 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 Visit 1, during screening/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 Visit 1.

• Immunoglobulin or blood products within 4 weeks of Visit 1.

• Treatment with Gemfibrozil within 4 weeks of Visit 1.

• Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the follow-up period.

• Investigational products within 4 months or 5 half-lives of Visit 1. 27 Potent inducers/inhibitors of cytochrome P450 3A4 within 4 weeks of Visit.

• Treatment with simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to 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 estradiol containing combined oral contraceptives.

• Concurrent enrolment in another clinical study.

• Participant treated with any investigational drug within 30 days prior to 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.

• Current smokers or participants with smoking history ≥ 10 pack-years.

• 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 Visit 1.

• Major surgery within 8 weeks prior to Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during the screening, treatment or follow-up periods.