STOP-PAD Trial Evaluates Juventas' JVS-100 Gene Therapy for Wound Healing

November 9, 2018—The STOP-PAD trial of SDF1 plasmid treatment for patients with peripheral artery disease examined revascularization therapy combined with intramuscular JVS-100 (Juventas Therapeutics), which is a nonviral gene therapy that activates endogenous regenerative repair pathways. Findings from the STOP-PAD trial, which used a novel design to investigate JVS-100, were presented by Mehdi H. Shishehbor, MD, at VIVA 2018, the Vascular Interventional Advances annual conference held November 5–8 in Las Vegas, Nevada.

The background of the trial is that the efficacy of biologic therapies for critical limb ischemia (CLI) remains elusive, partly because of limitations in trial design and patient selection.

As summarized in the VIVA announcement, the investigators in this double-blind, placebo-controlled, phase 2B trial randomized 109 patients with CLI (Rutherford class 5 or 6) to 8- or 16-mg intramuscular injections of a placebo versus JVS-100. Patients were eligible if they persistently had reduced forefoot perfusion by toe-brachial index (TBI) or skin perfusion pressure after successful revascularization with angiographic demonstration of tibial arterial flow to the ankle.

The primary efficacy endpoint of 6-month wound healing score was assessed by an independent wound core laboratory. The primary safety endpoint was major adverse limb events (MALEs). The mean patient age was 71 years, 33% were women, 79% had diabetes, and 8% had end-stage renal disease.

The investigators reported that TBI after revascularization was 0.26, 0.27, and 0.26 among the three groups (placebo, 8-mg, and 16-mg injections, respectively). Only 32% of wounds were completely healed at 6 months, without any differences between the three groups (31%, 33%, and 33%, respectively). Similarly, there were no significant changes in TBI at 6 months. Six (5.5%) patients died and four (3.6%) had major amputations. Rates of MALEs at 6 months were 24%, 29%, and 11%, respectively.

Although safe, JVS-100 failed to improve wound healing or hemodynamic measures at 6 months with only one-third of CLI wounds healing at 6 months despite successful revascularization These findings highlight the need for additional research on therapies that can improve microcirculation in these patients, concluded the STOP-PAD investigators at VIVA.