Table 1:
Investigational drugs in systemic sclerosis with published or announced Phase I, II or III clinical trials
| Molecules | Characteristics | Potential mechanisms of action in SSc | Development advancement in SSc | Reference on clinicaltrial.gov |
|---|---|---|---|---|
| Abituzumab | Mono-clonal antibody | Inhibitor of integrins from the αV class, with impact on activation of latent TGF-β and inhibition of FAK dependent activation of Rho dependent profibrotic pathways | Phase II in SSc-ILD | NCT02745145 |
| Abatacept | fusion protein | CTLA-4 dependent inhibition of co-stimulation leading to decreased Th1, 2, and B cell activation. | Phase II in early dcSSc | NCT02161406 |
| AVID200 | fusion protein | Selective inhibitor of TGF-β1 and 3 | Phase I in early dcSSc | NCT03831438 |
| Belimumab | Mono-clonal antibody | Selective inhibition of BAFF/BLyS, with impact on B-cell survival and maturation. | Phase II in early dcSSc | NCT01670565 |
| Belumosudil (KD025) | selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) | Selective ROCK-2 inhibitor that may inhibit myofibroblast activation and increase pro-resolving properties/efferocytosis of macrophages. | Phase II in early dcSSc |
NCT03919799 NCT04680975 |
| CM-101 | Mono-clonal antibody | Selective targeting of CCL-24, with subsequent inhibition of the homing of immune cells to tissue thus obtaining an anti-fibrotic effect | Phase II awaited in dcSSc and lcSSc | NA |
| Dasatinib | Oral small molecule | Senolytic agents that target senescent fibroblasts, responsible for an excessive production of IL-6 and TGF-β | Phase I/II in SSc-ILD | NCT00764309 |
| Fasudil | cyclic nucleotide-dependent protein kinase inhibitor | RhoA/ROCK inhibitor that may inhibit myofibroblast activation and increase pro-resolving properties/efferocytosis of macrophages. | Phase III | NCT00498615 |
| Fresolimumab | Mono-clonal antibody | Inhibitor of TGF-β1, 2 and 3 | Phase I in early dcSSc | NCT01284322 |
| IVIg | serum IgG fraction pooled from several thousands of donors | Targets and neutralizes auto-antibodies/immune complexes, inhibits monocyte activation, limits M1 and M2 activation | Phase II in early dcSSc |
NCT04137224 NCT04138485 NCT01785056 |
| JAK inhibitors: Tofacitinb (pan-JAK inhibitor) Itacitinib (JAK1 inhibitor) | Oral small molecule | Inhibits the signaling of key cytokines and mediators of fibroblast activation (TGF-β non-canonical pathway, IL-6) and macrophage activation (IFNg, IL-13, IL-4), B-effector cell activation. | Phase I/II in early dcSSc |
NCT03274076 NCT04789850 |
| Metelimumab (CAT-192) | Mono-clonal antibody | Inhibitor of TGF-β1 | Phase I/II in early dcSSc | NCT00043706 |
| MT-7117 | synthetic, oral, non-peptide small molecule | selective agonist of MC1R, that decrease the expression and impact of IL-6 and TGF-β, increase pro-resolving properties/efferocytosis of macrophages. | Phase II in early dcSSc | NCT04440592 |
| Pirfenidone | Oral small molecule | Suspected inhibition of TGF-β signaling | Phase II in SSc-ILD |
NCT03221257 NCT01933334 |
| Rituximab | Mono-clonal antibody | Anti-CD20 mab targeting B-cell, with subsequent impact of IL-6 release and potential impact on autoantibody production | Phase II in PAH-associated SSc | NCT01086540 |
| Romilkimab (SAR156597) | Mono-clonal antibody | Inhibits IL-13 and IL-14 signaling, leading to limited M2 and myofibroblasts activation | Phase II in early dcSSc | NCT02921971 |
| SAR100842 | selective oral antagonist of LPA1 | may inhibit myofibroblast activation through its impact on RhoA-ROCK signaling and increase pro-resolving properties/efferocytosis of macrophages. | Phase II in early dcSSc | NCT01651143 |
| Ziritaxestat (GLPG1690) | Oral autotaxin inhibitor | Inhibit the production of LPA producing enzyme autotaxin with subsequent inhibition of myofibroblast activation through its impact on TGF-β non-canonical signaling and increase pro-resolving properties/efferocytosis of macrophages. | Phase II in early dcSSc | NCT03798366 |