Trial Outcomes & Findings for Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease) (NCT NCT02719184)

NCT ID: NCT02719184

Last Updated: 2024-08-16

Results Overview

The absolute change from baseline at Week 156 in adjusted lung density (ALD) based on Percentile Density at 15% (PD15) adjusted for lung volume was reported. The ALD was calculated as: Percentile Density at 15% (PD15) \[gram/Liter (L)\] \* (Inspiratory volume \[L\]/predicted total lung volume \[L\]). The absolute change from baseline in ALD gram/Liter (g/L) was analyzed by Mixed Model for Repeated Measures (MMRM).

Recruitment status

COMPLETED

Target enrollment

463 participants

Primary outcome timeframe

Up to Week 156. Change from baseline value at Week 156 was reported.

Results posted on

2024-08-16

Participant Flow

The overall objective of this study is to explore, if any of the biomarkers (soluble, functional imaging and physiological) assessed within healthy subjects, patients with Chronic Obstructive Pulmonary Disease (COPD) and patients with COPD and Alpha-1 Antitrypsin (A1AT) deficiency are correlated to COPD disease progression, particularly emphysema progression over 156 weeks.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.

Participant milestones

Participant milestones
Measure	Healthy Subjects All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I 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 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 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 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.
Overall Study STARTED	62	123	130	129	19
Overall Study Per-Protocol Set (Biomarker Subjects)	61	122	127	127	19
Overall Study COMPLETED	56	101	110	93	10
Overall Study NOT COMPLETED	6	22	20	36	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Healthy Subjects All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I 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 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 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 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.
Overall Study Other than listed	1	12	13	22	9
Overall Study Withdrawal by Subject	5	3	6	6	0
Overall Study Lost to Follow-up	0	4	1	3	0
Overall Study Protocol Violation	0	3	0	2	0
Overall Study Adverse Event	0	0	0	3	0

Baseline Characteristics

Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Subjects n=62 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=123 Participants 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 n=130 Participants 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 n=129 Participants 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 n=19 Participants 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.	Total n=463 Participants Total of all reporting groups
Age, Continuous	54.0 Years STANDARD_DEVIATION 6.8 • n=62 Participants	61.9 Years STANDARD_DEVIATION 6.2 • n=123 Participants	61.8 Years STANDARD_DEVIATION 5.3 • n=130 Participants	62.9 Years STANDARD_DEVIATION 5.6 • n=129 Participants	52.8 Years STANDARD_DEVIATION 9.0 • n=19 Participants	60.7 Years STANDARD_DEVIATION 6.8 • n=463 Participants
Sex: Female, Male Female	23 Participants n=62 Participants	37 Participants n=123 Participants	52 Participants n=130 Participants	49 Participants n=129 Participants	3 Participants n=19 Participants	164 Participants n=463 Participants
Sex: Female, Male Male	39 Participants n=62 Participants	86 Participants n=123 Participants	78 Participants n=130 Participants	80 Participants n=129 Participants	16 Participants n=19 Participants	299 Participants n=463 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=62 Participants	2 Participants n=123 Participants	1 Participants n=130 Participants	3 Participants n=129 Participants	1 Participants n=19 Participants	7 Participants n=463 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=62 Participants	121 Participants n=123 Participants	127 Participants n=130 Participants	124 Participants n=129 Participants	18 Participants n=19 Participants	451 Participants n=463 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=62 Participants	0 Participants n=123 Participants	2 Participants n=130 Participants	2 Participants n=129 Participants	0 Participants n=19 Participants	5 Participants n=463 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=62 Participants	0 Participants n=123 Participants	1 Participants n=130 Participants	1 Participants n=129 Participants	0 Participants n=19 Participants	2 Participants n=463 Participants
Race (NIH/OMB) Asian	8 Participants n=62 Participants	16 Participants n=123 Participants	7 Participants n=130 Participants	6 Participants n=129 Participants	0 Participants n=19 Participants	37 Participants n=463 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=130 Participants	0 Participants n=129 Participants	0 Participants n=19 Participants	0 Participants n=463 Participants
Race (NIH/OMB) Black or African American	2 Participants n=62 Participants	1 Participants n=123 Participants	4 Participants n=130 Participants	3 Participants n=129 Participants	0 Participants n=19 Participants	10 Participants n=463 Participants
Race (NIH/OMB) White	52 Participants n=62 Participants	106 Participants n=123 Participants	117 Participants n=130 Participants	119 Participants n=129 Participants	19 Participants n=19 Participants	413 Participants n=463 Participants
Race (NIH/OMB) More than one race	0 Participants n=62 Participants	0 Participants n=123 Participants	1 Participants n=130 Participants	0 Participants n=129 Participants	0 Participants n=19 Participants	1 Participants n=463 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=130 Participants	00 Participants n=129 Participants	0 Participants n=19 Participants	0 Participants n=463 Participants
Adjusted lung density (ALD)	88.50 gram/Liter STANDARD_DEVIATION 13.90 • n=55 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.	86.20 gram/Liter STANDARD_DEVIATION 21.38 • n=100 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.	72.42 gram/Liter STANDARD_DEVIATION 21.69 • n=89 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.	54.81 gram/Liter STANDARD_DEVIATION 23.08 • n=89 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.	50.86 gram/Liter STANDARD_DEVIATION 18.15 • n=13 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.	73.62 gram/Liter STANDARD_DEVIATION 24.92 • n=346 Participants • Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments.

PRIMARY outcome

Timeframe: Up to Week 156. Change from baseline value at Week 156 was reported.

Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=41 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=64 Participants 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 n=51 Participants 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 n=37 Participants 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 n=5 Participants 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.
Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume	-0.27 gram/Liter (g/L) Standard Error 1.00	-3.15 gram/Liter (g/L) Standard Error 0.79	-5.04 gram/Liter (g/L) Standard Error 0.84	-4.74 gram/Liter (g/L) Standard Error 1.04	-6.13 gram/Liter (g/L) Standard Error 2.51

PRIMARY outcome

Timeframe: Up to Week 156

The annual rate of lung function decline based on Forced Expiratory Volume in 1 second (FEV1) was reported. The annual rate was estimated from a random slope and intercept model with fixed categorical effects of diagnosis group, fixed continuous effects of time \[Year\], and including diagnosis group-by-time interaction. Random effect was included for subject specific intercept and time. Within-subject errors are modelled by an unstructured variance-covariance matrix.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=55 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=106 Participants 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 n=101 Participants 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 n=90 Participants 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 n=14 Participants 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.
Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1)	-25.7 milliliter / year [mL/year] Standard Error 11.4	-24.4 milliliter / year [mL/year] Standard Error 8.9	-44.9 milliliter / year [mL/year] Standard Error 9.6	-59.3 milliliter / year [mL/year] Standard Error 11.4	-87.5 milliliter / year [mL/year] Standard Error 28.0

PRIMARY outcome

Timeframe: Up to Week 156

Number of participants by the category of number of exacerbations (no exacerbation, 1 exacerbation, or \>= 2 exacerbations) during study was reported.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=61 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=122 Participants 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 n=127 Participants 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 n=127 Participants 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 n=19 Participants 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.
Number of Participants by the Category of Number of Exacerbations During Study 0	59 Participants	89 Participants	66 Participants	41 Participants	2 Participants
Number of Participants by the Category of Number of Exacerbations During Study 1	1 Participants	23 Participants	24 Participants	30 Participants	4 Participants
Number of Participants by the Category of Number of Exacerbations During Study >= 2	1 Participants	10 Participants	37 Participants	56 Participants	13 Participants

PRIMARY outcome

Timeframe: Up to 156 weeks

The duration of exacerbations for each subject was calculated as: sum of duration of episodes during study (days)\*(365.25/ number of days in study).

Outcome measures

Outcome measures
Measure	Healthy Subjects n=2 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=33 Participants 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 n=61 Participants 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 n=86 Participants 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 n=17 Participants 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.
Duration of Exacerbations During Study (Per Year)	13.1 days/year Standard Deviation 5.2	9.7 days/year Standard Deviation 13.0	18.0 days/year Standard Deviation 19.4	19.7 days/year Standard Deviation 24.2	17.8 days/year Standard Deviation 16.7

PRIMARY outcome

Timeframe: Up to 156 weeks

Number of participants with at least moderate exacerbation during study by the category of number of moderate exacerbation (no moderate exacerbation, 1 moderate exacerbation, or \>= 2 moderate exacerbations) was reported.

Outcome measures

Outcome measures
Measure	Healthy Subjects n=61 Participants All eligible healthy subjects were included in this group. The observational period is 156 weeks.	COPD GOLD I n=122 Participants 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 n=127 Participants 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 n=127 Participants 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 n=19 Participants 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.
Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations 0	60 Participants	93 Participants	73 Participants	48 Participants	4 Participants
Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations 1	1 Participants	20 Participants	22 Participants	29 Participants	8 Participants
Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations >= 2	0 Participants	9 Participants	32 Participants	50 Participants	7 Participants

PRIMARY outcome

Timeframe: Up to 156 weeks

Number of participants with severe exacerbations during study by the category of number of severe exacerbations (no severe exacerbation, 1 severe exacerbation, or \>= 2 severe exacerbations) was reported.