Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of AZD5069 in patients with bronchiectasis.

Official Title
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A Phase II Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy of 28-Day Oral Administration of AZD5069 Twice Daily in Patients With Bronchiectasis

Conditions
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Bronchiectasis, Lung Disease, Respiratory Diseases

Intervention / Treatment
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* Drug: AZD5069
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, or female of non-child bearing potential; ie, women who are permanently or surgically sterilised or post-menopausal. Aged 18 to 80 years inclusive at screening (Visit 1) Have a clinical diagnosis of idiopathic or post infective bronchiectasis as diagnosed with a historical high resolution computerised tomography (HRCT) or bronchogram Be sputum producers with a history of chronic expectoration on most days of most weeks of the year. Patients should have a history of spontaneously producing sputum on a daily basis and should be able to provide at least 2 of the 3 required baseline sputum samples with an average of 3 mL or more. Be on a stable treatment regimen, as judged by the investigator. Exclusion Criteria: Any clinically significant disease or disorder Patients with other latent or chronic infections or at risk of infection within 90 days before Visit 2 An acute exacerbation or acute respiratory infection (upper or lower) requiring oral steroids or antibiotics within 30 days prior to Visit 2 An FEV1 of <30% of predicted normal at Visit 1 Patients who have received live or live-attenuated vaccine in the 2 weeks prior to dosing (Visit 2) Concomitant diagnosis of significant pulmonary disease other than bronchiectasis or COPD, including symptomatic asthma and allergic bronchopulmonary aspergillosis Bronchiectasis associated with a generalised immunodeficiency disorder, where manifestations other than bronchiectasis predominate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Treatment arm AZD5069 | Drug: AZD5069<br>* Oral dose bid<br>|
| Placebo Comparator: 2<br>Placebo dose. | Drug: Placebo<br>* Oral dose bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of the Percentage Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Change From Baseline in Weight of 24-hour Sputum Collection | Patients collected all sputum produced during a 24-hour period at baseline and Day 28. | Baseline and end of treatment (Day 28) | 
| Change From Baseline in Slow Vital Capacity (SVC) | Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. SVC is the measure of the change in volume of gas in the lungs from complete inspiration to complete expiration. | Baseline to end of treatment (Day 28) | 
| Change From Baseline in Forced Vital Capacity (FVC) | Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FVC is the maximum volume of air which can be exhaled or inspired during a forced maneuver. | Baseline to end of treatment (Day 28) | 
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 is the volume expired in the first second of maximal expiration after a full inspiration. | Baseline to end of treatment (Day 28) | 
| Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) | Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEF25-75 is flow rate during the middle half of forced vital capacity (25%-75% of the total volume (FVC) exhaled). | Baseline to end of treatment (Day 28) | 
| Transition Dyspnea Index (TDI) at End of Treatment (Day 28) | TDI measures changes in dyspnea severity from the baseline as established by the Baseline Dyspnea Index (BDI). TDI is an interviewer-administered rating of severity of dyspnea that assesses Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort domains on a 7-point scale ranging from -3 (major deterioration) to +3 (major improvement). Total score ranges from -9 to +9. The lower the score, the more deterioration in severity of dyspnea. | Baseline to end of treatment (Day 28) | 
| Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card | The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement. | Baseline and Last 7 days on treatment | 
| Change From Baseline for the Symptom Scores of the Bronkotest Diary Card | The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, number of puffs of inhalers, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement. | Baseline and Last 7 days on treatment | 
| Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) | SGRQ-C total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). The SGRQ-C contains 3 domains: Symptom (distress due to respiratory symptoms), Activity (disturbance of physical activity) and Impact (overall impact on daily life and well being). All three domains with scale from 0 (best health status) to 100 (worst possible status). | Baseline and end of treatment (Day 28) | 
| Ratio of Interleukin-1 Beta (IL-1β) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin-6 (IL-6) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Growth-related Oncogene-α (GRO-α) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin-8 (IL-8) in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Neutrophil Elastase Activity in Sputum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Serum Amyloid A (SAA) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of C-reactive Protein (CRP) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Growth-related Oncogene-α (GRO-α) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin-6 (IL-6) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin-1 Beta (IL-1β) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin-8 (IL-8) in Serum at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits. | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchiectasis, Neutrophil, Respiratory disease, Sputum