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

Boehringer Ingelheim

Status: Completed

Conditions: Pulmonary Emphysema; Pulmonary Disease, Chronic Obstructive

Study type: Observational

Funder types: Industry

Identifiers

NCT02719184

352.2069

Details and patient eligibility

About

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.

Enrollment: 463 patients

Sex: All

Ages: 40 to 60 years old

Volunteers: Accepts Healthy Volunteers

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:

  1. mild: post-broncho-dilator FEV1 >=80% of predicted normal (GLI 2012 and JRS 2014) at Visit 1
  2. moderate: 50%<= post-broncho-dilator FEV1 < 80% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1
  3. 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:

  1. Put the subject at risk because of participation in the study
  2. 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

Trial design

463 participants in 5 patient groups

Healthy subjects

Description:

All eligible healthy subjects were included in this group. The observational period is 156 weeks.

COPD GOLD I

Description:

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 1 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD GOLD II

Description:

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 2 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD GOLD III

Description:

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 3 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD and A1AT Deficiency

Description:

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) and Alpha one anti-trypsin (A1AT) deficiency were included in this group. The observational period is 156 weeks.