Efficacy and Safety of Three Inhaled Dose Levels of AZD1402 Administered for Four Weeks in Adults With Asthma on Medium Dose Inhaled Corticosteroids

• Status: Recruiting
• Trial end date: 2022-06-15
• Target enrollment: 0
• Participant gender: All

Summary

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 dose ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose ICS with LABA for Part 1 (separate inhalers or combination product) and medium dose ICS-LABA as a combination product for Part 2 at Screening.

Part 2 will be initiated for each dose level following evaluation of safety and PK at the relevant dose level in Part 1. 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.

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

Details

• Lead Sponsor: AstraZeneca

Criteria

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.

• 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.

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

• 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 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: Demonstration of reversibility to inhaled bronchodilators at Screening. Documented treatment with medium dose ICS-LABA for at least 12 months prior to Screening. 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. Have had at least one severe asthma exacerbation in the 12 months prior to Screening. Pre bronchodilator FEV1 of 60% to 80% (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.

• For Part 2: Pre-bronchodilator FEV1 of 60% to 80% (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:

• 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.

• Clinically important pulmonary disease other than asthma.

• History or clinical suspicion of any clinically relevant or active disease or disorder.

• Diagnosis of / suspected COVID-19 infection with associated pneumonia / pneumonitis.

• Participants with a positive test result for COVID-19.

• History of cancer within the last 10 years, any history of lymphoma or lung cancer is strictly exclusionary.

• 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, including hepatitis B or C, human immunodeficiency virus (HIV), 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.

• Pre-bronchodilator FEV1 decrease or increase ≥ 20%.

• 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-participant 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 and during Run-in.