Clinical trial NCT02719184: Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease)
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®].
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Disease, Chronic Obstructive
Pulmonary Emphysema
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-03-25
Enrollment: 463
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy volunteers and COPD patients

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume
timeFrame: Up to Week 156. Change from baseline value at Week 156 was reported.
measure: Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Up to Week 156
measure: Number of Participants by the Category of Number of Exacerbations During Study
timeFrame: Up to Week 156
measure: Duration of Exacerbations During Study (Per Year)
timeFrame: Up to 156 weeks
measure: Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations
timeFrame: Up to 156 weeks
measure: Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations
timeFrame: Up to 156 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Torrance
country: United States
facility: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Brussels
country: Belgium
facility: Brussels - UNIV St-Pierre
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: University of Alberta Hospital (University of Alberta)
state: Alberta
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Quebec
country: Canada
facility: IUCPQ (Laval University)
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Helsinki
country: Finland
facility: HYKS Keuhkosairauksien tutkimusyksikkö
city: Turku
country: Finland
facility: TYKS
city: Frankfurt
country: Germany
facility: IKF Pneumologie GmbH & Co. KG
city: Großhansdorf
country: Germany
facility: Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
city: Hannover
country: Germany
facility: Fraunhofer ITEM
city: Lübeck
country: Germany
facility: KLB Gesundheitsforschung Lübeck GmbH
city: Kagoshima, Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital
city: Osaka, Kishiwada
country: Japan
facility: Kishiwada City Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka City University Hospital
city: Tokyo, Shinagawa-ku
country: Japan
facility: Showa University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St. Mary's Hospital
city: Bialystok
country: Poland
facility: Respiratory Medicine Centre, private prac., Bialystok
city: Gdansk
country: Poland
facility: University Clinical Center, Gdansk
city: Warsaw
country: Poland
facility: Institute of Tuberculosis & Lung Disease, Warsaw
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Quirónsalud Madrid
city: Lund
country: Sweden
facility: Skånes universitetssjukhus, Lund
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Crapo J, Gupta A, Lynch DA, Vogel-Claussen J, Watz H, Turner AM, Mroz RM, Janssens W, Ludwig-Sengpiel A, Beck M, Langellier B, Ittrich C, Risse F, Diefenbach C. FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD. BMJ Open. 2021 Mar 22;11(3):e042526. doi: 10.1136/bmjopen-2020-042526.