AZD1419 Ph2a Study
Condition: Asthma
MeSH terms: Asthma
Intervention: AZD1419; Placebo
Intervention description: Inhaled AZD1419 administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events; Inhaled Placebo administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is Placebo 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: inhaled; TLR9 agonist; withdrawal design; loss of control

Summary:

      Ph2a study planned to be run at approximately 16-18 sites in 4 EU countries (Denmark,
      Hungary, Poland and Sweden) enrolling approximately 170 patients to ensure 70 randomized
      patients with eosinophilic, moderate to severe asthma. The patients will receive 13 once
      weekly inhaled doses of the study drug. Treatment is initiated on top of their ICS/LABA
      controller medication, which is then tapered down and withdrawn during a period of 3 weeks
      and during the last 3 weeks of treatment the study drug is given as monotherapy. SABA is used
      as reliever medication during the whole study period. Primary endpoint is Loss of asthma
      control. When the endpoint is met, patients will resume their ICS/LABA, will be followed for
      an additional 4 weeks and will thereafter discontinue the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients 18 years and above

          -  Physician-diagnosed asthma requiring treatment with ICS and a long-acting beta agonist
             (LABA). Patients must have taken ICS plus LABA controller medication for at least 3
             months prior to screening

          -  Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50% predicted

          -  Female patients must be 1 year post-menopausal, surgically sterile, or using an
             acceptable method of contraception

          -  Male patients must be surgically sterile or using an acceptable method of
             contraception (defined as barrier methods in conjunction with spermicides) from the
             first dose of the IMP and until 1 month after the last dose of the IMP to prevent
             pregnancy in a partner

          -  Blood eosinophil levels ≥ 250 cells/μL at screening OR a history of blood eosinophil
             levels ≥ 250 cells/μL at any time in the preceding 2 years AND blood eosinophil levels
             ≥ 150 cells /μL at screening. The eosinophilia must be believed to be due to asthma
             and not have other known causes, e.g. helminth infection

          -  ACQ-5 score ≤1.5 at screening

          -  ACQ-5 score ≤0.75 at randomization

          -  Documentation of any of the following within 5 years prior to Visit 1:

               -  Proof of post-bronchodilator reversibility in FEV1 of ≥12% and ≥200 mL

               -  Proof of a positive response to a methacholine or histamine challenge (a decrease
                  in FEV1 by 20% [PC20] at ≤8 mg/mL)

               -  Proof of positive response to mannitol challenge (a decrease in FEV1 by 15%
                  [PD15] at ≤635 mg or a >10% decrease in FEV1 between consecutive doses)

               -  Proof of diurnal variability in PEF >20% over the course of 24 hours in at least
                  4 out of 7 consecutive days If historical documentation is not available, proof
                  of reversibility or a positive response to a methacholine, histamine or mannitol
                  challenge or diurnal variation must be demonstrated according to above and
                  documented during Visit 1

        Exclusion Criteria:

          -  Clinically significant lung disease other than asthma (eg, chronic obstructive
             pulmonary disease, cystic fibrosis, allergic bronchopulmonary aspergillosis, active
             tuberculosis).

          -  History of autoimmune disease including but not limited to Wegener's granulomatosis,
             system lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, multiple
             sclerosis, autoimmune thrombocytopenia, primary biliary cirrhosis or any other
             autoimmune disease considered clinically relevant by the investigator

          -  Ongoing allergen immunotherapy or plans to begin such therapy during the study period

          -  DLco ≤ 60% of the lower limit of normal

          -  Breast feeding, pregnancy or intention to become pregnant during the course of the
             study

          -  Changes in chest X-ray suggesting clinically significant parenchymal disease other
             than asthma