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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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®].

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02719184
• Other study ID #: 352.2069
• Status: Completed
• Start date: April 13, 2016
• Est. completion date: June 14, 2021

Study information

• Verified date: January 2022
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 464
• Est. completion date: June 14, 2021
• Est. primary completion date: June 14, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Emphysema
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Emphysema

Locations

Country	Name	City	State
Belgium	Brussels - UNIV St-Pierre	Brussels
Belgium	UZ Leuven	Leuven
Canada	University of Alberta Hospital (University of Alberta)	Edmonton	Alberta
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	IUCPQ (Laval University)	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Denmark	Aarhus University Hospital	Aarhus N
Denmark	Gentofte Hospital	Hellerup
Denmark	Hvidovre Hospital	Hvidovre
Finland	HYKS Keuhkosairauksien tutkimusyksikkö	Helsinki
Finland	TYKS, Keuhkosairauksien klinikka, Turku	Turku
Germany	IKF Pneumologie GmbH & Co. KG	Frankfurt
Germany	Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH	Großhansdorf
Germany	Fraunhofer ITEM	Hannover
Germany	KLB Gesundheitsforschung Lübeck GmbH	Lübeck
Japan	Kagoshima University Hospital	Kagoshima, Kagoshima
Japan	Showa University Fujigaoka Hospital	Kanagawa, Yokohama
Japan	Kishiwada City Hospital	Osaka, Kishiwada
Japan	Osaka City University Hospital	Osaka, Osaka
Japan	Showa University Hospital	Tokyo, Shinagawa-ku
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Eunpyeong St. Mary's Hospital	Seoul
Poland	Respiratory Medicine Centre, private prac., Bialystok	Bialystok
Poland	University Clinical Center, Gdansk	Gdansk
Poland	Institute of Tuberculosis & Lung Disease, Warsaw	Warsaw
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Hospital Quirónsalud Madrid	Pozuelo de Alarcón
Sweden	Skånes universitetssjukhus, Lund	Lund
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Royal Free Hospital	London
United Kingdom	Medicines Evaluation Unit	Manchester
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	National Jewish Health	Denver	Colorado
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Diagnostics Research Group	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Finland,  Germany,  Japan,  Korea, Republic of,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of exacerbations		156 weeks
Primary	Severity of exacerbations		156 weeks
Primary	Lung function decline		156 weeks
Primary	Number of exacerbations		156 weeks
Primary	Change of lung density assessed by computed tomography scan		156 weeks

External Links

•   Related Info