Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Moderate COPD, Severe COPD, Very Severe COPD, chronic obstructive pulmonary disease, AZD6793, IRAK4 Inhibitor
Brief summary
This Phase IIb dose-ranging study will evaluate the efficacy and safety of 2 different doses of AZD6793 compared with placebo tablets in participants with moderate to very severe chronic obstructive pulmonary disease.
Detailed description
A Multicentre, Parallel-group, Phase IIb, Randomised, Double-blind, Placebo-controlled, 3-Arm, 24-Week Study to Evaluate the Efficacy and Safety of AZD6793 Tablets in Adult Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (PRESTO) Approximately 350 sites globally will participate in this study. Approximately 970 participants will be randomized to AZD6793 or Placebo. Following CSP V.3.0, participants will be randomized in a 1:1:1 ratio of two doses of AZD6793 vs Placebo.
Interventions
DRUGAZD6793
Oral dosage
OTHERPlacebo
Oral dosage
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinded
Intervention model description
Participants will be randomized in a ratio of 1:1:1 to receive Dose 1 of AZD6793, Dose 2 of AZD6793 or matching placebo.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be ≥40 years of age at the time of signing the informed consent. * Documented primary diagnosis of COPD for at least 12 months prior to enrolment. * Pre-BD FEV1/FVC \< 0.7 at Visit 1 and pre- and post-BD FEV1/FVC \< 0.7, and post-BD FEV1 ≥ 25% to \< 80% of predicted normal at Visit 2. * Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations in the 12 months prior to screening. * Documented stable regimen of inhaled triple maintenance therapy or inhaled dual maintenance therapy for ≥ 3 months prior to screening. * CAT score ≥ 10 at Visit 1. * Current or ex-smokers with a cigarette smoking history of ≥ 10 pack-years. * Participants who are clinically stable and free from an exacerbation of COPD for 4 weeks prior to Visit 1 and are also exacerbation free for at least 4 weeks (28 days) prior to Visit 3 (randomisation). * Negative pregnancy test at Visit 1 and Visit 3 for Women Of Child-Bearing Potential (WOCBP).
Exclusion criteria
* Clinically important pulmonary disease other than COPD (eg, asthma \[current diagnosis per GINA or other accepted guidelines\], active pulmonary infection, clinically significant bronchiectasis when bronchiectasis is the predominant diagnosis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency or primary ciliary dyskinesia). * Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms. * Any unstable disorder, including, but not limited to, CV, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment. * Significant left heart failure. * Unstable angina, acute coronary syndrome/acute myocardial infarction or coronary intervention with percutaneous coronary intervention/coronary artery bypass graft within 6 months of randomisation, uncontrolled arrhythmia, or cardiomyopathy, clinically significant aortic stenosis, or signs of pulmonary oedema or volume overload. * Pulmonary arterial hypertension, either idiopathic or due to connective tissue or thromboembolic disease. * History of another underlying condition that predisposes the participant to infections. * History of ulcerative colitis, Crohn's disease, or microscopic colitis diagnosed by either a gastroenterologist or by histopathology. * Abnormal laboratory findings. * Participants with evidence of active liver disease and/or evidence of chronic liver disease. * Participants with history of HIV infection or who test positive for HIV. * History of lung volume reduction surgery. * Current or history of malignancy within 5 years before the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualised rate of moderate or severe COPD exacerbations | From baseline up to 24 Weeks | The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 24 Weeks treatment period compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first moderate or severe COPD exacerbation | From baseline up to 24 Weeks | To evaluate the effect of AZD6793 as compared to placebo on COPD exacerbations from baseline up to 24 Weeks |
| Annualised rate of COPD exacerbations associated with emergency room visits, urgent care visits, or hospitalisations | From baseline up to 24 Weeks | To evaluate the effect of AZD6793 as compared to placebo on COPD exacerbations from baseline up to 24 Weeks |
| Annualised rate of severe COPD exacerbations | From baseline up to 24 Weeks | To evaluate the effect of AZD6793 as compared to placebo on COPD exacerbations from baseline up to 24 Weeks |
| Annualised rate of COPDCompEx events | From baseline up to 24 Weeks | To evaluate the effect of AZD6793 as compared to placebo on COPDCompEx events from baseline up to 24 Weeks |
| Time to first COPDCompEx event | From baseline up to 24 Weeks | To evaluate the effect of AZD6793 as compared to placebo on COPDCompEx events from baseline up to 24 Weeks |
| Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | From baseline to Week 12 and Week 24 | Change from baseline in pre-BD FEV1 at Week 12 and Week 24 compared to placebo |
| Change from baseline in post-bronchodilator (post-BD) forced expiratory volume in 1 second (FEV1) | From baseline to Week 12 and Week 24 | Change from baseline in post-BD FEV1 at Week 12 and Week 24 compared to placebo |
| Change from baseline in Breathlessness, Cough and Sputum Scale (BCSS) total score | From baseline over 24 Weeks | Change from baseline in BCSS total score over 24 Weeks compared to placebo. The BCSS is a 3-item questionnaire rating breathlessness, sputum, and cough on a 5 point Likert scale from 0 (no symptoms) to 4 (severe symptoms). The BCSS has a scoring range of 0-12 with higher scores indicative of greater COPD impact on health status. |
| Change from baseline in COPD Assessment Test (CAT) total score | From baseline over 24 Weeks | Change from baseline in the CAT total score over 24 weeks CAT is an 8-item PRO that measures the impact of COPD on the health status of patients with COPD. The CAT has a scoring range of 0-40 with higher scores indicative of greater COPD impact on health status. |
| Change from baseline in St George's Respiratory Questionnaire (SGRQ) total and domain scores | From baseline over 24 Weeks | Participants achieving a clinically meaningful improvement from baseline in SGRQ total score (4-point score decrease) over 24 weeks. SGRQ is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating better health status. |
| Measurement of plasma concentrations of AZD6793 at specific timepoints | From baseline to Week 4, Week 12 and Week 24 | To assess the pharmacokinetics (PK) of AZD6793 in participants with moderate to very severe COPD |
Countries
Argentina, Australia, Bulgaria, Canada, Chile, China, Denmark, Germany, Greece, Hungary, India, Italy, Japan, Mexico, Peru, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORDave Singh, MD
Medicines Evaluation Unit, Manchester University NHS Foundations Trust, Manchester, United Kingdom
Outcome results
None listed