AZD1419 Ph2a Study

• Status: Completed
• Trial end date: 2018-09-25
• Target enrollment: 0
• Participant gender: All

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 Treatment is initiated on top of their ICS/LABA controller medication, which is then tapered down and withdrawn during a period of 3 weeks and during the last 3 weeks of treatment the study drug is given as monotherapy.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.

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

Details

• Lead Sponsor: AstraZeneca

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