RXi Pharmaceuticals’ first clinical candidate, RXI-109, is a self-delivering RNAi compound (sd-rxRNA) being developed to reduce dermal scarring following planned surgeries. RXI-109 is designed to reduce the expression of connective tissue growth factor (CTGF), a critical regulator of several biological pathways involved in fibrosis, including scar formation in the skin.
After the successful filing of an IND, single- and multiple dose, dose escalation Phase 1 clinical trials evaluating RXI-109 in a surgical setting were initiated in 2012 in healthy volunteers (RXI-109-1201 and RXI-109-1202, respectively). These two trials demonstrated the safety and tolerability of RXI-109, and also provided the first evidence of clinical activity in a surgical setting.
In early November 2013, we initiated our Phase 2 program with RXI-109. In the first Phase 2 study (RXI-109-1301), subjects with a long hypertrophic scar in the lower abdominal received scar revision surgery and subsequent treatment with RXI-109 over the first month after surgery. Subjects received RXI-109 or placebo on a blinded basis at the distal ends of their revised scar, leaving a central untreated section of the scar. Each subjects’ revised scar area provides the opportunity to compare the appearance of the revised areas after treatment with RXI-109 or placebo or when left untreated, allowing for the within-subject comparison of the three revised scar segments. Enrollment and dosing in this trial is complete.
In addition, a second Phase 2 trial was initiated in 2014 in which subject’s with two similar keloids were enrolled (RXI-109-1401). After the two keloids were surgically removed, one keloid was treated with RXI-109 and one was treated with placebo, again allowing for the within subject comparison of the treatments. Enrollment and dosing in this trial is complete.
Preliminary data from the first Phase 2 hypertrophic scar trial were used to help design a third Phase 2 trial, RXI-109-1402. Study 1402 is being conducted in subjects in which one long or two shorter hypertrophic scars are surgically revised. Treatment of the revised areas with RXI-109 is being compared directly to revised areas that are left untreated on the same subject. Preliminary data from the initial two cohorts of Study 1402 demonstrated that scars were less visible after six doses of RXI-109 over the course of three months. Based in part on this new information, two more cohorts were added to this trial in November 2015. Two extended dosing regimens are currently being evaluated to determine if clinical results are improved if dosing is continued further into the extended proliferation phase of wound healing that leads to hypertrophic scarring.
Lastly, RXI-109 is being evaluated in a Phase 1/2 trial for its safety, tolerability and potential activity in the eye. RXI-109-1501 is a dose escalation trial in which subjects with late stage, wet age-related macular degeneration (AMD) with the risk of subretinal fibrosis will be treated with RXI-109. As in dermal scarring, CTGF is known to play a role in retinal scarring. Reduction of CTGF in the eye by RXI-109 treatment may reduce the formation of retinal fibrosis that often accompanies late stage AMD and contributes to vision loss. The main goals of this study are to establish safety and tolerability of RXI-109 in the eye, and to gain a preliminary indication of whether RXI-109 interrupts the scarring process common to these late stage AMD subjects.
You may find more information on our trials at ClinicalTrials.gov