Chronic Kidney Disease, Type 2 Diabetes Mellitus
Conditions
Brief summary
Researchers are looking for a better way to treat people who have chronic kidney disease (CKD), a long-term, progressive decrease in the kidneys' ability to work properly. When CKD happens in people with type 2 diabetes mellitus, a condition characterized by high blood sugar levels, CKD is also referred to as diabetic kidney disease (DKD). FIGARO-BM is an add-on study in which blood draws that were collected in the FIGARO-DKD study are further analyzed. No additional blood draws (also referred to as biological samples) or data will be obtained from the participants, nor will any additional or new study intervention be introduced. No visit or patient contact other than for obtaining the agreement by the patients (also called informed consent) will be required. Inflammation and scarring are both seen as responsible for worsening of chronic kidney disease. There is much information from animal studies that the study treatment finerenone (BAY94-8862) works against inflammation and against scarring (also called fibrosis) in organs such as the kidney. In this exploratory study researchers want to learn more about the study treatment finerenone (BAY94-8862). To find this out, this study will examine substances called biomarkers in blood draws from participants in the FIGARO-DKD study. Biomarkers are used as indicators of biological processes, disease processes or responses to medication. The biomarkers that will be examined stand for inflammation, organ scarring (also called fibrosis), blood vessel function and congestion. The main question of this study is whether there are differences between these biomarkers in the group of participants who received finerenone and the group of participants who received a placebo in the FIGARO-DKD study. A placebo looks like a treatment but does not have any medicine in it. To answer this question, the researchers will compare the levels of these biomarkers between the two groups at different time points after starting the study treatment. Blood samples for this study will be obtained from FIGARO-DKD study sites with a high number of participants who had been treated with finerenone or placebo for at least 24 months. This information will be combined with other information from biomarker examinations already available in the FIGARO-DKD study.
Interventions
Oral tablet; starting at 10 mg or 20 mg; once daily; received in previous interventional Phase 3 trial FIGARO-DKD; no new intervention was administered in this biomarker study.
DRUGPlacebo
Oral tablet; starting at 10 mg or 20 mg; once daily; received in previous interventional Phase 3 trial FIGARO-DKD; no new intervention was administered in this biomarker study.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* This study will only include participants who were enrolled in the FIGARO-DKD study (NCT02545049) and had received up to 20 mg finerenone or placebo for ≥24 months. * For each participant, pharmacokinetic (PK) plasma samples from Visit 3 and at least 2 other Visits (Visit 5, Visit 8, Visit 11) must be available on storage from the main study FIGARO-DKD.
Exclusion criteria
* Participants which did not show overall compliance of 80 to 120% with study intervention in FIGARO-DKD. * Participants which were not part of the full analysis set (FAS) of FIGARO-DKD. * Participants with known fatal outcome. * Participants with baseline estimated glomerular filtration rate (eGFR) ≤25 mL/min/1.73m\^2. * Participants with low baseline risk (normal albuminuria and eGFR≥60 mL/min/1.73m\^2). * Sponsor request (after discussion with the investigator), for reasons such as a significant protocol deviation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | At 4 months (Visit 3) of treatment and 36 months (Visit 11) of treatment | The normalized protein expression (NPX) of biomarker levels were analyzed for the set of 27 pre-defined plasma biomarkers. NPX is a unit on log2-scale that is logarithmically related to protein concentration. Linear NPX (2\^NPX) was calcuated for descriptive analyses of the biomarker levels at each visit. Ratios of Visit 11 (36 months of treatment) to Visit 3 (4 months of treatment) were calculated to show the change in the plasma biomarker levels. Visit 3 (4 months of treatment) data were considered as baseline for the biomarker measurements as no pre-dose samples were available from FIGARO-DKD. Note, NPX units (Olink concentration units) are always relative units and can only be interpreted in the context of an individual study, i.e. to compare two conditions or timepoints (change in NPX). Equal nominal concentration values (same NPX units) for two different biomarkers measured by Olink Explore does not mean that both markers have the same absolute concentration. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, Finland, Hong Kong, Israel, Italy, Japan, Netherlands, Portugal, Russia, Singapore, South Korea, Spain, Sweden, Taiwan, United States
Participant flow
Recruitment details
The study was conducted at multiple centers in 21 countries/regions between 18 August 2021 (first subject first visit) and 31 December 2021 (last subject last visit).
Pre-assignment details
Overall, 952 participants from previous FIGARO-DKD study (NCT02545049) were screened for this FIGAGRO-BM study. Of the 952 screened (i.e. signed informed consent available either for this FIGARO-BM study or for the protocol addendum for FIGARO-DKD), 1 participant was a screening failure and 30 participants missed treatment and/or biomarker data at Visit 3 or 11 in FIGARO-DKD. The remaining 921 participants were included in the modified biomarker full analysis set of FIGAGRO-BM study.
Participants by arm
| Arm | Count |
|---|---|
| Finerenone Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy in previous interventional Phase 3 trial FIGARO-DKD. No new intervention was administered in this biomarker study. | 478 |
| Placebo Participants received matching placebo once daily in addition to standard of care therapy in previous interventional Phase 3 trial FIGARO-DKD. No new intervention was administered in this biomarker study. | 443 |
| Total | 921 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Exclusion from mBFAS | 5 | 25 |
Baseline characteristics
| Characteristic | Finerenone | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 63.55 years STANDARD_DEVIATION 9.5 | 63.84 years STANDARD_DEVIATION 9.57 | 64.15 years STANDARD_DEVIATION 9.65 |
| Plasma biomarker levels after 4 months of treatment Aminopeptidase N (P15144) | 1.224 Linear NPX (2^NPX) STANDARD_DEVIATION 1.273 | NA Linear NPX (2^NPX) | 1.248 Linear NPX (2^NPX) STANDARD_DEVIATION 1.3 |
| Plasma biomarker levels after 4 months of treatment C-C motif chemokine 14 (Q16627) | 3.013 Linear NPX (2^NPX) STANDARD_DEVIATION 1.667 | NA Linear NPX (2^NPX) | 3.056 Linear NPX (2^NPX) STANDARD_DEVIATION 1.426 |
| Plasma biomarker levels after 4 months of treatment C-C motif chemokine 16 (O15467) | 1.625 Linear NPX (2^NPX) STANDARD_DEVIATION 1.776 | NA Linear NPX (2^NPX) | 1.633 Linear NPX (2^NPX) STANDARD_DEVIATION 1.637 |
| Plasma biomarker levels after 4 months of treatment C-C motif chemokine 2 (P13500) | 3.065 Linear NPX (2^NPX) STANDARD_DEVIATION 1.285 | NA Linear NPX (2^NPX) | 3.209 Linear NPX (2^NPX) STANDARD_DEVIATION 1.367 |
| Plasma biomarker levels after 4 months of treatment CCN family member 2 (P29279) | 1.245 Linear NPX (2^NPX) STANDARD_DEVIATION 1.585 | NA Linear NPX (2^NPX) | 1.258 Linear NPX (2^NPX) STANDARD_DEVIATION 1.36 |
| Plasma biomarker levels after 4 months of treatment CCN family member 4 (O95388) | 1.600 Linear NPX (2^NPX) STANDARD_DEVIATION 1.337 | NA Linear NPX (2^NPX) | 1.578 Linear NPX (2^NPX) STANDARD_DEVIATION 1.374 |
| Plasma biomarker levels after 4 months of treatment Collagen alpha-1(I) chain (P02452) | 0.646 Linear NPX (2^NPX) STANDARD_DEVIATION 1.675 | NA Linear NPX (2^NPX) | 0.693 Linear NPX (2^NPX) STANDARD_DEVIATION 1.497 |
| Plasma biomarker levels after 4 months of treatment C-X-C motif chemokine 16 (Q9H2A7) | 1.341 Linear NPX (2^NPX) STANDARD_DEVIATION 1.586 | NA Linear NPX (2^NPX) | 1.353 Linear NPX (2^NPX) STANDARD_DEVIATION 1.338 |
| Plasma biomarker levels after 4 months of treatment Decorin (P07585) | 1.523 Linear NPX (2^NPX) STANDARD_DEVIATION 1.233 | NA Linear NPX (2^NPX) | 1.526 Linear NPX (2^NPX) STANDARD_DEVIATION 1.233 |
| Plasma biomarker levels after 4 months of treatment Dickkopf-related protein 3 (Q9UBP4) | 1.827 Linear NPX (2^NPX) STANDARD_DEVIATION 1.541 | NA Linear NPX (2^NPX) | 1.925 Linear NPX (2^NPX) STANDARD_DEVIATION 1.46 |
| Plasma biomarker levels after 4 months of treatment E-selectin (P16581) | 1.235 Linear NPX (2^NPX) STANDARD_DEVIATION 1.828 | NA Linear NPX (2^NPX) | 1.200 Linear NPX (2^NPX) STANDARD_DEVIATION 1.577 |
| Plasma biomarker levels after 4 months of treatment Interleukin-15 receptor subunit alpha (Q13261) | 1.678 Linear NPX (2^NPX) STANDARD_DEVIATION 1.432 | NA Linear NPX (2^NPX) | 1.614 Linear NPX (2^NPX) STANDARD_DEVIATION 1.45 |
| Plasma biomarker levels after 4 months of treatment Matrilysin (P09237) | 19.618 Linear NPX (2^NPX) STANDARD_DEVIATION 1.148 | NA Linear NPX (2^NPX) | 18.956 Linear NPX (2^NPX) STANDARD_DEVIATION 1.203 |
| Plasma biomarker levels after 4 months of treatment Matrix metalloproteinase-9 (P14780) | 1.329 Linear NPX (2^NPX) STANDARD_DEVIATION 2.202 | NA Linear NPX (2^NPX) | 1.176 Linear NPX (2^NPX) STANDARD_DEVIATION 1.985 |
| Plasma biomarker levels after 4 months of treatment Metalloproteinase inhibitor 1 (P01033) | 1.818 Linear NPX (2^NPX) STANDARD_DEVIATION 1.45 | NA Linear NPX (2^NPX) | 1.824 Linear NPX (2^NPX) STANDARD_DEVIATION 1.349 |
| Plasma biomarker levels after 4 months of treatment Pappalysin-1 (Q13219) | 0.171 Linear NPX (2^NPX) STANDARD_DEVIATION 3.066 | NA Linear NPX (2^NPX) | 0.164 Linear NPX (2^NPX) STANDARD_DEVIATION 2.762 |
| Plasma biomarker levels after 4 months of treatment Plasminogen activator inhibitor 1 (P05121) | 1.349 Linear NPX (2^NPX) STANDARD_DEVIATION 2.148 | NA Linear NPX (2^NPX) | 1.261 Linear NPX (2^NPX) STANDARD_DEVIATION 1.868 |
| Plasma biomarker levels after 4 months of treatment Protein AMBP (P02760) | 1.595 Linear NPX (2^NPX) STANDARD_DEVIATION 1.226 | NA Linear NPX (2^NPX) | 1.611 Linear NPX (2^NPX) STANDARD_DEVIATION 1.225 |
| Plasma biomarker levels after 4 months of treatment Proto-oncogene tyrosine-protein kinase Src (P12931) | 1.770 Linear NPX (2^NPX) STANDARD_DEVIATION 2.614 | NA Linear NPX (2^NPX) | 1.535 Linear NPX (2^NPX) STANDARD_DEVIATION 2.229 |
| Plasma biomarker levels after 4 months of treatment Retinoic acid receptor responder protein 2 (Q99969) | 2.201 Linear NPX (2^NPX) STANDARD_DEVIATION 1.58 | NA Linear NPX (2^NPX) | 2.252 Linear NPX (2^NPX) STANDARD_DEVIATION 1.418 |
| Plasma biomarker levels after 4 months of treatment Thrombospondin-2 (P35442) | 1.421 Linear NPX (2^NPX) STANDARD_DEVIATION 1.655 | NA Linear NPX (2^NPX) | 1.452 Linear NPX (2^NPX) STANDARD_DEVIATION 1.649 |
| Plasma biomarker levels after 4 months of treatment Transforming growth factor beta-1 proprotein (P01137) | 1.480 Linear NPX (2^NPX) STANDARD_DEVIATION 1.327 | NA Linear NPX (2^NPX) | 1.425 Linear NPX (2^NPX) STANDARD_DEVIATION 1.349 |
| Plasma biomarker levels after 4 months of treatment Transforming growth factor beta receptor type 3 (Q03167) | 1.583 Linear NPX (2^NPX) STANDARD_DEVIATION 1.631 | NA Linear NPX (2^NPX) | 1.776 Linear NPX (2^NPX) STANDARD_DEVIATION 1.624 |
| Plasma biomarker levels after 4 months of treatment Tumor necrosis factor receptor superfamily member 1A (P19438) | 2.105 Linear NPX (2^NPX) STANDARD_DEVIATION 1.606 | NA Linear NPX (2^NPX) | 2.107 Linear NPX (2^NPX) STANDARD_DEVIATION 1.575 |
| Plasma biomarker levels after 4 months of treatment Urokinase plasminogen activator surface receptor (Q03405) | 1.744 Linear NPX (2^NPX) STANDARD_DEVIATION 1.699 | NA Linear NPX (2^NPX) | 1.725 Linear NPX (2^NPX) STANDARD_DEVIATION 1.398 |
| Plasma biomarker levels after 4 months of treatment Uromodulin (P07911) | 0.582 Linear NPX (2^NPX) STANDARD_DEVIATION 1.752 | NA Linear NPX (2^NPX) | 0.699 Linear NPX (2^NPX) STANDARD_DEVIATION 1.531 |
| Plasma biomarker levels after 4 months of treatment von Willebrand factor (P04275) | 3.200 Linear NPX (2^NPX) STANDARD_DEVIATION 1.793 | NA Linear NPX (2^NPX) | 2.338 Linear NPX (2^NPX) STANDARD_DEVIATION 1.629 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 173 Participants | 324 Participants | 151 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 293 Participants | 576 Participants | 283 Participants |
| Sex: Female, Male Female | 120 Participants | 232 Participants | 112 Participants |
| Sex: Female, Male Male | 358 Participants | 689 Participants | 331 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers
The normalized protein expression (NPX) of biomarker levels were analyzed for the set of 27 pre-defined plasma biomarkers. NPX is a unit on log2-scale that is logarithmically related to protein concentration. Linear NPX (2\^NPX) was calcuated for descriptive analyses of the biomarker levels at each visit. Ratios of Visit 11 (36 months of treatment) to Visit 3 (4 months of treatment) were calculated to show the change in the plasma biomarker levels. Visit 3 (4 months of treatment) data were considered as baseline for the biomarker measurements as no pre-dose samples were available from FIGARO-DKD. Note, NPX units (Olink concentration units) are always relative units and can only be interpreted in the context of an individual study, i.e. to compare two conditions or timepoints (change in NPX). Equal nominal concentration values (same NPX units) for two different biomarkers measured by Olink Explore does not mean that both markers have the same absolute concentration.
Time frame: At 4 months (Visit 3) of treatment and 36 months (Visit 11) of treatment
Population: Participants in mBFAS with available data for each biomarker measurement
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Plasminogen activator inhibitor 1 (P05121) | 0.945 Ratio | Standard Deviation 2.089 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Transforming growth factor beta-1 proprotein (P01137) | 1.122 Ratio | Standard Deviation 1.312 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | CCN family member 2 (P29279) | 1.083 Ratio | Standard Deviation 1.548 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Pappalysin-1 (Q13219) | 1.088 Ratio | Standard Deviation 3.371 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Urokinase plasminogen activator surface receptor (Q03405) | 1.109 Ratio | Standard Deviation 1.661 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Matrilysin (P09237) | 1.014 Ratio | Standard Deviation 1.125 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 14 (Q16627) | 1.072 Ratio | Standard Deviation 1.617 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Proto-oncogene tyrosine-protein kinase Src (P12931) | 0.926 Ratio | Standard Deviation 2.902 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 16 (O15467) | 1.044 Ratio | Standard Deviation 1.607 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Transforming growth factor beta receptor type 3 (Q03167) | 1.133 Ratio | Standard Deviation 1.687 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Collagen alpha-1(I) chain (P02452) | 1.101 Ratio | Standard Deviation 1.68 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Protein AMBP (P02760) | 1.034 Ratio | Standard Deviation 1.168 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Decorin (P07585) | 1.086 Ratio | Standard Deviation 1.202 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | CCN family member 4 (O95388) | 1.109 Ratio | Standard Deviation 1.266 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 2 (P13500) | 1.001 Ratio | Standard Deviation 1.329 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Matrix metalloproteinase-9 (P14780) | 1.074 Ratio | Standard Deviation 2.303 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Uromodulin (P07911) | 0.980 Ratio | Standard Deviation 1.513 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | E-selectin (P16581) | 1.009 Ratio | Standard Deviation 1.681 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Interleukin-15 receptor subunit alpha (Q13261) | 1.121 Ratio | Standard Deviation 1.402 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Thrombospondin-2 (P35442) | 1.054 Ratio | Standard Deviation 1.533 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Aminopeptidase N (P15144) | 1.005 Ratio | Standard Deviation 1.263 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Retinoic acid receptor responder protein 2 (Q99969) | 1.035 Ratio | Standard Deviation 1.569 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | von Willebrand factor (P04275) | 0.979 Ratio | Standard Deviation 1.773 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-X-C motif chemokine 16 (Q9H2A7) | 1.058 Ratio | Standard Deviation 1.562 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Tumor necrosis factor receptor superfamily member 1A (P19438) | 1.151 Ratio | Standard Deviation 1.506 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Dickkopf-related protein 3 (Q9UBP4) | 1.050 Ratio | Standard Deviation 1.452 |
| Finerenone | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Metalloproteinase inhibitor 1 (P01033) | 1.056 Ratio | Standard Deviation 1.456 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Dickkopf-related protein 3 (Q9UBP4) | 1.055 Ratio | Standard Deviation 1.427 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Matrilysin (P09237) | 1.062 Ratio | Standard Deviation 1.201 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | von Willebrand factor (P04275) | 1.131 Ratio | Standard Deviation 1.765 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | CCN family member 4 (O95388) | 1.164 Ratio | Standard Deviation 1.329 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Transforming growth factor beta-1 proprotein (P01137) | 1.184 Ratio | Standard Deviation 1.369 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Transforming growth factor beta receptor type 3 (Q03167) | 1.224 Ratio | Standard Deviation 1.649 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Interleukin-15 receptor subunit alpha (Q13261) | 1.179 Ratio | Standard Deviation 1.442 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Metalloproteinase inhibitor 1 (P01033) | 1.105 Ratio | Standard Deviation 1.381 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Pappalysin-1 (Q13219) | 1.273 Ratio | Standard Deviation 3.034 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Proto-oncogene tyrosine-protein kinase Src (P12931) | 1.000 Ratio | Standard Deviation 2.492 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Protein AMBP (P02760) | 1.045 Ratio | Standard Deviation 1.166 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Uromodulin (P07911) | 0.956 Ratio | Standard Deviation 1.388 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Aminopeptidase N (P15144) | 1.020 Ratio | Standard Deviation 1.316 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Tumor necrosis factor receptor superfamily member 1A (P19438) | 1.184 Ratio | Standard Deviation 1.516 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Plasminogen activator inhibitor 1 (P05121) | 0.972 Ratio | Standard Deviation 1.909 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | CCN family member 2 (P29279) | 1.103 Ratio | Standard Deviation 1.395 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Urokinase plasminogen activator surface receptor (Q03405) | 1.127 Ratio | Standard Deviation 1.379 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 14 (Q16627) | 1.092 Ratio | Standard Deviation 1.401 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 16 (O15467) | 1.055 Ratio | Standard Deviation 1.416 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Collagen alpha-1(I) chain (P02452) | 1.112 Ratio | Standard Deviation 1.534 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Decorin (P07585) | 1.088 Ratio | Standard Deviation 1.25 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Matrix metalloproteinase-9 (P14780) | 1.080 Ratio | Standard Deviation 2.108 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | E-selectin (P16581) | 1.010 Ratio | Standard Deviation 1.432 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Thrombospondin-2 (P35442) | 1.056 Ratio | Standard Deviation 1.533 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | Retinoic acid receptor responder protein 2 (Q99969) | 1.022 Ratio | Standard Deviation 1.517 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-X-C motif chemokine 16 (Q9H2A7) | 1.063 Ratio | Standard Deviation 1.33 |
| Placebo | Mean Change in Plasma Biomarker Levels After 36 Months of Treatment Versus 4 Months of Treatment in a Set of 27 Pre-defined Biomarkers | C-C motif chemokine 2 (P13500) | 1.003 Ratio | Standard Deviation 1.409 |
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Matrilysin (P09237) was analyzed.p-value: =0.001t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of von Willebrand factor (P04275) was analyzed.p-value: =0.002t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of CCN family member 4 (O95388) was analyzed.p-value: =0.044t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of TGF beta-1 proprotein (P01137) was analyzed.p-value: =0.044t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of TGF beta receptor type 3 (Q03167) was analyzed.p-value: =0.127t-test, 2 sided
Comparison: The NPX differences (corresponding to log-transformed ratio to baseline) of IL-15 receptor subunit alpha (Q13261) was analyzed.p-value: =0.21t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Metalloproteinase inhibitor 1 (P01033) was analyzed.p-value: =0.215t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Pappalysin-1 (Q13219) was analyzed.p-value: =0.215t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Proto-oncogene c-Src (P12931) was analyzed.p-value: =0.745t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Protein AMBP (P02760) was analyzed.p-value: =0.762t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Uromodulin (P07911) was analyzed.p-value: =0.762t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Aminopeptidase N (P15144) was analyzed.p-value: =0.762t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of TNFRSF1A (P19438) was analyzed.p-value: =0.762t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Plasminogen activator inhibitor 1 (P05121) was analyzed.p-value: =0.917t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of CCN family member 2 (P29279) was analyzed.p-value: =0.917t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of uPAR (Q03405) was analyzed.p-value: =0.917t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of C-C motif chemokine 14 (Q16627) was analyzed.p-value: =0.917t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of C-C motif chemokine 16 (O15467) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Collagen alpha-1(I) chain (P02452) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Decorin (P07585) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX differences (corresponding to log-transformed ratio to baseline) of C-C motif chemokine 2 (P13500) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Matrix metalloproteinase-9 (P14780) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX differences (corresponding to log-transformed ratio to baseline) of E-selectin (P16581) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Thrombospondin-2 (P35442) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of RARRES2 (Q99969) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of C-X-C motif chemokine 16 (Q9H2A7) was analyzed.p-value: =0.979t-test, 2 sided
Comparison: The NPX difference (corresponding to log-transformed ratio to baseline) of Dickkopf-related protein 3 (Q9UBP4) was analyzed.p-value: =0.979t-test, 2 sided