Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease)

Study Overview
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Brief Summary
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The study will include 60 healthy subjects (ex-smoker without any airflow limitation), 125 COPD GOLD (global initiative for chronic obstructive lung disease) I , 125 COPD GOLD II, 125 COPD GOLD III and up to 20 patients with COPD and A1AT (Alpha1-Antitrypsin) deficiency (ZZ genotype). Soluble and imaging biomarkers will be investigated addressing different aspects of disease pathways postulated to be relevant for COPD progression.

Official Title
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Observational Study in Healthy Subjects and Patients With COPD to Assess the Relationship Between Clinical, Imaging and Biomarker Measurements, and Progression of Emphysema Over Three Years [FOOTPRINTS®].

Conditions
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Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion Criteria Male or female healthy subjects or COPD (GOLD I to III) outpatients with or without A1AT deficiency Ex-smokers for at least 9 months with a smoking history of >=20 pack years Signed informed consent consistent with ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) guidelines prior to participation in the study, which includes the application of study restrictions Age >= 40 and <=70 years Body mass index (BMI) of >= 18 and <= 35 kg/m2 (<= 30 kg/m2 in the MRI subset) Ability to perform all study related procedures including technically acceptable pulmonary function tests, body plethysmography, DLCO ( Diffusing Capacity of the lungs for Carbon Monoxide) , sputum induction (if applicable), chest CT (Computed Tomography) and MRI (if applicable) Inclusion Criteria Specific for Patients with COPD - Patients must have a current diagnosis of COPD made by a physician prior to or during Visit 1 and a mMRC (Modified Medical Research Council Dyspnea Scale) score of 1 or more. The diagnosis of COPD must be in accordance with GOLD Guidelines and must be documented by the following criteria: Known relatively stable airway obstruction with a post-bronchodilator FEV1 (Forced Expiratory Volume in first second)/FVC (Forced Vital Capacity) < 70 % The current COPD must be mild, moderate or severe based on lung functions and symptoms and the clinical situation must have stabilized for at least 4 weeks prior to Visit 1. The following definitions adapted from the GOLD Guidelines apply: mild: post-broncho-dilator FEV1 >=80% of predicted normal (GLI 2012 and JRS 2014) at Visit 1 moderate: 50%<= post-broncho-dilator FEV1 < 80% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1 severe: 30%<= post-bronchodilator FEV1 <50% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1 Patients must be on stable therapy (not limited to respiratory medication) for the last 4 weeks prior to Visit 1 Inclusion Criteria Specific Patients with COPD and A1AT Deficiency - Documented A1AT deficiency of ZZ genotype Inclusion Criteria Specific Healthy Subjects Normal lung function values at Visit 1 with a documented post-bronchodilator FEV1 >=80% of predicted normal (GLI 2012 and JRS 2014) and a post-bronchodilator FEV1/FVC >= lower limit of normal Mean post DLCO over all acceptable measurements at Visit 1 of >= 70% of predicted normal Further inclusion criteria apply Exclusion Criteria: General Exclusion Criteria Previous participation in this study or participation in another trial with an investigational drug within 6 weeks prior to Visit 1 or during the study Significant pulmonary disease or other significant medical conditions* (as determined by medical history, examination and clinical investigations at screening) that may in the opinion of the investigator result in any of the following: Put the subject at risk because of participation in the study Cause concern regarding the subject's ability to participate in this study *e.g. rheumatoid arthritis, inflammatory bowel disease, severe liver disease, psoriasis, hematological, infectious and psychiatric diseases Documented history of asthma. For allergic rhinitis or atopy, source documentation to verify that the subject does not have asthma Planned surgery during the study expected to interfere with study procedures and outcome Blood withdrawal of more than 100 mL within the past 6 weeks prior to Visit 1 and between Visit 1 and 2 Significant alcohol or drug abuse within past 2 years prior to Visit 1 Women who are pregnant, nursing or plan to become pregnant while in the study Place of permanent residence of less than 3 months prior to Visit 1 For the MRI subset: subject who do not meet the following criteria for the MRI assessment at Visit 2: systolic blood pressure between 90 and 180 mmHg (SBP), diastolic blood pressure between 50 and 110 mmHg (DBP), pulse rate between 40 and 110 bpm, ear temperature between 35 - 37.5 C, and a glomerular filtration rate (GFR) >= 30 mL/min (GFR must not be older than 14 days from the MRI assessment) Exclusion Criteria Specific for Patients with COPD - Respiratory tract infection or COPD exacerbation in the 4 weeks prior to Visit 1 or during the screening period prior to Visit 2, if rescheduling rules cannot be met Exclusion Criteria Specific Patients with COPD and A1AT Deficiency Newly added anti-inflammatory treatment within 4 weeks prior to Visit 1 Patients on treatment with PDE (Phosphodiesterase)-5 inhibitors (e.g. Roflumilast) and maintenance treatment Methylxanthines (e.g. Theophylline) Hospitalisation for respiratory failure during the year prior to Visit 1 A history of cystic fibrosis Clinical diagnosis of bronchiectasis requiring specific treatment Clinically relevant abnormal baseline hematology and blood chemistry Known active tuberculosis Patients with change in any therapy within 4 weeks prior to Visit 1 Current and planned A1AT augmentation therapy A malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed Inability to comply with restrictions regarding diet, life style and medication Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br> | |
| COPD GOLD I<br>Chronic obstructive pulmonary disease | |
| COPD GOLD II<br>Chronic obstructive pulmonary disease | |
| COPD GOLD III<br>Chronic obstructive pulmonary disease | |
| A1AT Deficiency<br>Alpha one anti-trypsin deficiency | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of exacerbations |  | 156 weeks | 
| Severity of exacerbations |  | 156 weeks | 
| Lung function decline |  | 156 weeks | 
| Number of exacerbations |  | 156 weeks | 
| Change of lung density assessed by computed tomography scan |  | 156 weeks |