Table 3.
Therapeutic biomarkers in IPF.
| Primary Outcome | Secondary Outcomes | Biomarkers Considered | Status and Results | ||
|---|---|---|---|---|---|
| INMARK study NCT02788474 Year: 2016 |
Type: RCT N. part: 347 Nintedanib vs. Placebo |
The rate of change (slope) in blood CRPM from baseline to week 12. | Percentage of patients with disease progression The rate of change in blood C1M from baseline to week 12 The rate of change in blood C3M from baseline to week 12 |
CRPM C3M C1M |
Status: completed Results: rate of change in CRPM is not a marker of response to nintedanib in patients with IPF The rate of change in CRPM from baseline to week 12 was −2.57 × 10−3 ng/mL/month in the nintedanib group and −1.90 × 10−3 ng/mL/month in the placebo group (between-group difference −0.66 × 10−3 ng/mL/month [95% CI −6.21 × 10−3 to 4.88 × 10−3]; p = 0.8146). |
| A Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of 28 Day Treatment with Fostair® Pressurized Metered-dose Inhaler (pMDI) 200/12 on Biomarkers of Platelet Adhesion in Patients with IPF NCT02048644 Year: 2014 |
Type: RCT N. part 20 beclomethasone/formoterol pMDI 100/6 mcg 2 puffs twice daily for 28 days vs. placebo |
Platelet-monocyte complex formation platelet P-selectin expression platelet fibrinogen binding |
FVC sputum eosinophils cells six minutes-walk d istance |
Platelet derived markers | Status: completed Results: Change from baseline spirometric measurements of FEV1(L), FEV/FVC % pred FEF25–75 were significantly improved following 28 days B/F by (mean ± SD), 0.88 ± 0.16 L (p = 0.03), 0.03 ± 0.03 (p = 0.03), 12.4 ± 19.1% (p = 0.02) respectively when compared to placebo. There was no change in quality of life or exercise measures. The effects of beclomethasone/formoterol in this study may represent delivery of corticosteroid to the peripheral airways ameliorating local injury and altering platelet activation |
| Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose-Escalation Study of STX-100 in Patients With IPF NCT01371305 Year: 2011 |
Type: RCT N. part: 41 SXT-100 vs. placebo in IPF |
Number of Participants with adverse events | Pharmacodinamic and pharmacokinetic parameters of BG00011 (STX-100) Percentage change from baseline in biomarkers solated from BAL Number of participants with treatment emergent antibodies to BG00011 |
The expression level of 7 genes; ALOX5, FN1, OLR1, PAI-1 (aka SERPINE 1), TGM2, TREM1, and ETS1 were assessed via BAL as well as a ratio of pSMAD2 to tSMAD2 levels. | Status: completed Results:/ |
| A Open-label, Multicenter Study, With a Single Intravenous Dose of QAX576 to Determine IL-13 Production in patients with IPF NCT00532233 Year: 2007 |
Type: open label clinical trial N. part: 52 QAX576 in IPF cohort |
To investigate the possibility that some IPF patients experience increased IL-13 production. Blood samples to be collected pre-dose and weekly after dosing. -To investigate the hypothesis that QAX576 will neutralize IL-13 in patients with IPF | To evaluate the changes in biomarkers in blood over time in patients with IPF. Serum samples will be obtained at pre-dose and 2 weeks post-dose. | IL-13 Other blood biomarkers |
Status: completed Results: the study was terminated early after 31 patients were enrolled and randomized to receive QAX576 due to slow enrolment rate. |
| Randomized, Double-Blind, Parallel Group, Placebo-Controlled, Multicenter, Exploratory Phase IIa Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 Administered for 12 Weeks in Subjects With IPF NCT02738801 Year: 2016 |
Type: RCT N. part: 23 GLPG1690 capsules, administered at a dose of 600 mg, orally QD vs. placebo in IPF cohort. |
Adverse events, pharmacodynamic and pharmacokinetics parameters, mean Peak Area Ratio of LPA C18:2 species in Blood and BALF | / | LPA C18:2 | Status: completed Results: concentrations of LPA C18:2 in plasma decreased after administration of GLPG1690 at the week 4 (p = 0.0001) and 12 (p = 0.0014) visits and return to baseline concentrations at the FU visit. In BALF, LPA C18:2 and LPA C20:4 concentrations are below the level of quantification for more than 25% of baseline samples obtained from patients in the GLPG1690 treatment group. |
| A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of GKT137831 in Patients with IPF NCT03865927 Year: 2020 |
Type: RCT N. part: 60 GKT137831 400 mg bid for 24 weeks vs. placebo |
Surrogate biomarker of oxidative stress by mass spectroscopy through 24 weeks (changes in concentrations of circulating o,o’-dityrosine) | Collagen degradation product (serum C1M) by enzyme linked immunoabsorbant assay through 24 weeks LFT Ambulatory ability by measuring walk distance in six-minutes Evaluation of safety by adverse events |
o,o’-dityrosine C1M |
Status: ongoing |
| Non-Interventional Collecting Evidences For ILD in Taiwan: Optimized Novel Therapy NCT04614441 Year: 2020 |
Type: observational prospective N. part: 500 IPF vs. PF-ILD vs. SSc-ILD on therapy with Nintedanib 150 mg bid |
Annual percentage of decline from baseline in FVC, %, DLCO, % and resting and exercise oxygen saturation (SpO2, %) per cohort of IPF, SSc-ILD, or PF-ILD | Time to first AE of IPF; or time to ILD worsening for SSc-ILD/PF-ILD after study enrolment Annual change from baseline in SGRQ for IPF or K-BILD for other ILDs, CAT, Berlin questionnaire and 6MWT Change from baseline in quantification of biomarkers Mortality |
Include but not limited to PDGF, VEGF, FGF, TGF-β1, HGF, MMPs: MMP-1, MMP-7, MMP-9, α-defensin 1, HMGB1, TIMP, HSP: HSP-27, bile acid conjugated, LPA, LPAR1, PGE2, IL: IL-1β, IL-4, IL-18, IL-13, IL-17, MCP-1, MIP-2, periostin, osteopontin, SP-A, SP-D, KL-6/MUC1, anti-HSP70, IgG BMP, CA-199, CRPM, CCL 2, CCL-18 | Status: ongoing |
| Targeted Removal of Pro-Inflammatory Cells: An Open Label Human Pilot Study in IPF NCT02874989 Year: 2016 |
Type: RCT N. part: 26 Dasatinib + Quercetin vs. placebo in IPF cohort |
Percentage of pro-inflammatory expressing cells (skin biopsy) Percentage of pro-inflammatory expressing cells (skin biopsy) BP, weight, HR, CBC, lipid panel, HBA1c, comprehensive metabolic panel, high sensitivity CRP, plasma IL-6, plasma PASP biomarkers, p16INK4a biomarker |
/ | high sensitivity CRP, plasma IL-6, plasma PASP biomarkers, p16INK4a biomarker | Status: ongoing |
| EXCHANGE-IPF NCT03584802 Year: 2018 |
Type: RCT N. part: 40 Therapeutic plasma exchanges vs. conventional treatment in AE of IPF |
Overall mortality at day 28 after initiation of therapy | […] Changes in lung injury biomarkers in plasma (KL-6, SP-D) between day 1 and day 90 Changes in circulating autoantibodies levels (anti-periplakin, anti-HSP70 and anti-vimentin antibodies) between day 1 and day 90 |
Injury biomarkers Circulating fibrocytes Auto-antibodies |
Status: ongoing |
RCT: randomized controlled trial; CRPM, C-reactive protein degraded by matrix metalloproteinase; pMDI, pressurized metered dose inhaler; FVC, forced vital capacity; FEV1, Forced Expiratory Volume in the 1st second; FEF, Forced mid-expiratory flow rate; SD, standard deviation; IPF, idiopathic pulmonary fibrosis; BAL, broncho alveolar lavage; IL-13, interleukin-13; C1M, Collagen 1 Degraded by Matrix Metalloproteinase-2/9/13; C3M, Collagen 3 Degraded by Matrix Metalloproteinase-9; ALOX5, Arachidonate 5-lipoxygenase; FN1, fibronectin 1; OLR1, Oxidized low density lipoprotein receptor 1; PAI-1, Plasminogen activator inhibitor-1; TGM2, Transglutaminase 2; TREM 1, Triggering receptor expressed on myeloid cells 1; ETS1, v-ets erythroblastosis virus E26 oncogene homolog 1; LPA, Lysophosphatidic Acid; BALF, broncho alveolar lavage fluid; LFT, lung function test; PF ILD, progressive fibrosing interstitial lung disease; Ssc ILD, systemic sclerosis interstitial lung disease; DLCO, diffusing capacity for carbon monoxide; AE, acute exacerbation; ILD, interstitial lung disease; SGRQ, Saint George Respiratory questionnaire; K-BILD, King’s Brief Interstitial Lung Disease questionnaire; CAT, Chronic obstructive pulmonary disease Assessment Test; 6MWT, 6 min walking test; PDGF, Platelet Derived Growth Factor; VEGF, Vascular Endothelial Growth Factor; FGF, Fibroblast Growth Factor; TGF-β1, Transforming Growth Factor β1; HGF, Hepatocyte Growth Factor; MMPs, metalloproteases; HMGB1, High Mobility Group Box 1; TIMP, Tissue of Metalloproteinase; HSP, Heat-Shock Protein; LPA, Lysophosphatidic Acid; LPAR1, Lysophosphatidic Acid Receptor 1; PGE2, Prostagladin E2; IL, Interleukin; MCP-1, Monocyte Chemoattractant Protein 1; MIP-2, Macrophage Inflammatory Protein 2; SP, surfactant protein; KL6/MUC1, Krebs von den Lungen-6; IgG, Immunoglobolin G; BMP, Bone Morphogenic Protein; CA-199, Carbonhydrate Antigen-199; CRMP, C-reactive protein degraded by matrix metalloproteinase-1/8; CCL, chemokine (C-C motif) ligand; BP, blood pressure; HR, heart rate; CBC, complete blood count; HBA1c, Hemoglobin A1c; CRP, C reactive protein; PASP, pulmonary artery systolic pressure.