Table 1.
Completed clinical trials evaluating anti-fibrotic drugs in organs other than the gut
| Parameter | Author | Study organ | Number of patents | Type of trial | Study drug | Mode of action | Outcome measures |
|---|---|---|---|---|---|---|---|
| Growth factors |
Noble
[95] |
Lung |
779 |
RCT, phase III |
Pirfenidone |
Inhibition of TGF-β |
Increased FVC in IPF |
| Trachtman
[98] |
Kidney |
16 |
Open-label, phase I |
Fresolimumab |
Antibody targeting all isoforms of TGF-β |
Safety, pharmacokinetics |
|
| Ferguson
[111] |
Skin |
223 |
RCT, phase I/II |
Avotermin |
Antibody targeting TGF-β3 |
Acceleration and permanent improvement in dermal scaring |
|
| Dillingh
[114] |
Lung |
29 |
RCT, phase I |
rhSAP |
Substitution of SAP |
Reduction in SAP levels and circulating fibrocytes in healthy control and IPF patients |
|
| Oxidative stress |
Raghu
[158] |
Lung |
88 |
RCT, phase II |
Etanercept |
Blockade of TNF |
Physiological and functional decrease in disease progression in IPF |
| Corren
[159] |
Lung |
219 |
RCT, phase II |
Lebrikizumab |
Antibody targeting IL-13 |
Improved lung function in asthmatic patients |
|
| Horton
[160] |
Lung |
23 |
RCT, phase III |
Thalidomide |
Anti-angiogenic and anti-inflammatory |
Improvement of cough and respiratory quality of life in IPF |
|
| Intracellular enzymes and receptors |
Richeldi
[162] |
Lung |
432 |
RCT, phase II |
BIBF 1120 |
Tyrosine kinase inhibitor |
Tendency towards reduced decline of lung function in IPF |
| Daniels
[108] |
Lung |
119 |
RCT, phase II/III |
Imatinib |
Tyrosine kinase inhibitor |
No effect on survival and lung function |
|
| ECM and other |
Couluris
[140] |
Lung |
20 |
Uncontrolled, interventional study, phase II |
Losartan |
AT1 antagonist |
Stabilization of lung function in IPF |
| el-Agroudy
[142] |
Kidney |
162 |
RCT, phase II |
Losartan |
AT1 antagonist |
Decreased TGF-β1 plasma levels and proteinuria in renal interstitial fibrosis |
|
| Kuhn
[182] |
Skin |
10 |
Prospective, open-label, phase II |
Bosentan |
Endothelin receptor antagonist |
Reduced skin thickening in systemic sclerosis |
|
| Diez
[141] |
Heart |
34 |
Uncontrolled, phase II |
Losartan |
AT1 antagonist |
Decreased myocardial collagen content and left ventricular chamber stiffness in hypertensive patients |
|
| De
[143] |
Liver |
39 |
RCT, phase II |
Losartan |
AT1 antagonist |
Reduction of portal pressure in patients with liver cirrhosis |
|
| King [183] | Lung | 616 | RCT | Bosentan | Endothelin receptor antagonist | Improvement of FVC and diffusing capacity in IPF |
AT1, angiotensin II receptor antagonist subtype 1; CXCL, CXC ligand; ECM, extracellular matrix; FVC, forced vital capacity; IL, interleukin; IPF, idiopathic pulmonary fibrosis; RCT, randomized controlled trial; SAP, serum amyloid P component; TGF-β, transforming growth factor beta; TNF, tumor necrosis factor.