Efficacy and Safety of Inhaled AZD1402 Administered for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids (APATURA)

This is an interventional treatment trial for Asthma focused on measuring AZD1402, placebo, Anticalin® protein, dry powder inhaler, inhaled corticosteroids, efficacy, safety Read More

Inclusion Criteria:

• Participants who have a documented clinical diagnosis of asthma for ≥ 12 months before Visit 1.
• Participants who are able to perform acceptable pulmonary function testing for FEV1.
• Participants who are able to demonstrate the ability to use the study inhalation device properly.
• Male participants must be surgically sterile or agree to use highly-effective contraceptives.
• All female participants must have a negative serum pregnancy test at Screening. Female participants of non-childbearing potential, Female participants of childbearing potential must have a negative urine pregnancy test before the administration of first dose of study intervention and must agree to use a highly-effective method of birth control.
• Participant is a non smoker or an ex-smoker with a total smoking history of less than 10 pack-years.
• Only for Part 1: Documented treatment with medium dose ICS with LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 3 months prior to Screening, during Screening and Run-in Periods and may be contained in a combination product or separate inhaler. No asthma exacerbations in last 12 months requiring oral or intravenous (IV) steroids or hospitalisation/ emergency room visit due to asthma. Pre-bronchodilator FEV1 ≥ 70% predicted at Screening and start of Run-in. Asthma Control Questionnaire 6 score of ≤ 1.0 at Screening and start of Run-in.
• Only for Part 2: Documented evidence of asthma. Documented treatment with medium-to-high dose ICS-LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 3 months prior to Screening, during Screening and Run-in Periods. If on asthma maintenance controller medications in addition to ICS-LABA, the dose of the additional controller medications must be stable for at least 3 months prior to Screening, during Screening and Run-in Periods. Have had at least one severe asthma exacerbation in the 3 years prior to Screening. Pre bronchodilator FEV1 of 50% to 85% (inclusive) predicted at Screening and start of Run-in. Blood eosinophil count of ≥ 150 cells/μL and FeNO ≥ 25 ppb at Screening. Asthma Control Questionnaire 6 score ≥ 1.5 at Screening.

Specific Randomisation Criteria at Visit 3

• For Part 1: Pre-bronchodilator FEV1 ≥ 70% predicted. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period (from Visit 2 to Visit 3) based on daily electronic diary (e-Diary). Minimum 80% compliance with ePRO completion. Asthma Control Questionnaire 6 score of ≤ 1.0. C-reactive protein < 5 mg/L on Day -1.
• For Part 2: Pre-bronchodilator FEV1 of 50% to 85% (inclusive) predicted. Asthma Control Questionnaire 6 score of ≥ 1.5. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period from (Visit 2 to Visit 3) based on daily e-Diary. Minimum 80% compliance with ePRO completion. C-reactive protein < 5 mg/L at Visit 2. A FeNO of ≥ 25 ppb.

Exclusion Criteria:

• Women who are pregnant or breastfeeding, or who are planning to become pregnant during the study.
• Known or suspected hypersensitivity including anaphylaxis/anaphylactoid reaction following any biologic therapy, or known history of drug hypersensitivity to any component of the study intervention formulation.
• Evidence of any active clinically important pulmonary disease other than asthma, within 5 years at screening.
• History of pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
• History or clinical suspicion of any clinically relevant or active disease or disorder.
• Diagnosis of / suspected COVID-19 infection with associated pneumonia / pneumonitis.
• Diagnosis of COVID--19 at screening and prior to randomisation.
• Current malignancy or history of malignancy.
• Significant history of recurrent or ongoing 'dry eye'.
• Diagnosis of Sjögren's syndrome.
• High risk of infection suggesting abnormal immune function.
• History of, or known significant infection or positivity at Screening period, including hepatitis B or C, or human immunodeficiency virus (HIV).
• Evidence of active or untreated latent tuberculosis infection.
• Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Screening and during Run-in.
• Clinically significant upper respiratory tract infection at Screening and during Run-in.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained.
• Any clinically important ECG abnormalities.
• Any clinically significant cardiac disease.
• Uncontrolled hypertension.
• History of life-threatening asthma attack or asthma attack requiring ventilation.
• Part 2 only: History of 3 or more severe asthma exacerbations.
• Daily rescue use of SABA ≥ 8 puffs for ≥ 3 consecutive days at any time during Run-in Period, before randomisation.
• History of anaphylaxis.
• Any clinically significant abnormalities in haematology.
• Alanine aminotransferase or AST level ≥ 3 times the upper limit of normal (ULN), confirmed by repeated testing during Screening Period.
• History of, drug or alcohol abuse within the past 2 years prior to Screening.
• Planned in-patient surgery, major dental procedure or hospitalisation during the study.
• Prior/Concomitant Therapy: Systemic corticosteroid use, AZD1402, marketed or investigational biologicals such as monoclonal antibodies or chimeric biomolecules, investigational nonbiologic drug within 60 days prior to Screening and during Run-in, any immunosuppressive therapy, Live or attenuated vaccine within 4 weeks of Screening and during Run-in, Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation, Immunoglobulin or blood products within 4 weeks of Screening and during Run-in, Any immunotherapy within 3 months of Screening and during Run-in.
• Part 1 only: Additional asthma maintenance controller medications in addition to ICS-LABA (eg, leukotriene receptor inhibitors, theophylline, LAMA, chromones) within 3 months of Screening period and during Run-in.