A Two-part Phase IIa Randomised, Double-blind, Placebo-controlled, Dose-ranging, Multi-centre Study to Assess Efficacy and Safety of Inhaled AZD1402 Administered as a Dry Powder for Four Weeks in Adults With Asthma on Medium-to-High Dose Inhaled Corticosteroids

D2912C00003

This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to assess the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a Lead-in Cohort for each dose level to evaluate the safety and pharmacokinetics (PK) in a population with asthma controlled on medium dose inhaled corticosteroids (ICS)-long acting beta agonists (LABA) before progressing to dosing in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose ICS with LABA for Part 1 and participants receiving treatment with medium-to-high dose ICS with LABA for Part 2 (separate inhalers or combination product). Part 2 will be initiated following evaluation of safety and PK at the relevant dose level in Part 1a. The entire study period for each participant in both Parts 1 and 2, is approximately 3.5 months; a 2-week Screening Period, a 4 week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of Follow-Up Period.

2021-03-12

2023-07-20

2023-07-20

Terminated

Early phase I

72

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 4 weeks 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 4 weeks prior to Screening, during Screening and Run-in Periods. Pre bronchodilator FEV1 of 40% 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 40% 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 70% compliance with ePRO completion. C-reactive protein \< 10 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. * History of severe COVID-19 infection requiring hospitalisation within the last 12 months or clinical history compatible with long COVID (symptoms beyond 12 weeks of acute infection). * Confirmed symptomatic COVID-19 infection during Screening, Run-in or 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 tuberculosis. * 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.

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2023-08-16