Three-Month Data Analyzed for Experimental Drug JVS-100 to Enhance Wound Healing in CLI
March 12, 2018—Results of the STOP-PAD trial were presented by Mehdi Shishehbor, DO, in a Late Breaking Trial session at the American College of Cardiology's (ACC) 67th annual scientific session held March 10–12 in Orlando, Florida.
STOP-PAD is evaluating the safety and efficacy of hSDF-1 plasmid (JVS-100, Juventas Therapeutics, Inc.) to enhance wound healing after open or endovascular revascularization of patients treated for critical limb ischemia (CLI). STOP-PAD is a phase 2, randomized, double-blind, placebo-controlled study.
JVS-100 is an experimental biologic therapy that delivers DNA that encodes proteins involved in the production of blood vessels. The drug is designed to improve blood flow in smaller blood vessels close to the skin surface where lesions can fester.
According to the ACC announcement, the study showed that patients with foot ulcers or gangrene who received JVS-100 did not show evidence of faster wound healing compared with those receiving a placebo. The investigators will continue to track patient outcomes for at least 12 months.
As summarized in the ACC press release, the STOP-PAD study enrolled 109 patients at 25 centers in the United States to assess whether JVS-100 helped wounds heal when used with revascularization. Patients were randomly assigned to receive either JVS-100 or a placebo in a series of two injections—one within 12 days of their revascularization procedure and the other 3 months later. Half of those receiving JVS-100 were given a higher dose of the experimental drug and half were given a lower dose.
All patients had undergone revascularization for CLI but showed poor blood flow to the toe (toe-brachial index [TBI] ≤ 0.51) after the procedure. Most of the patients in the trial had multiple illnesses, 90% had diabetes, and 7% were on dialysis.
The investigators tracked wound healing as well as rates of death, amputation, and major adverse limb events (MALEs) defined as major amputation, bypass, or balloon revascularization in the affected limb.
In the trial, approximately only one-quarter of patients' wounds had healed completely at 3 months after undergoing revascularization, whether they were treated with JVS-100 or placebo. In addition to low rates of wound healing, the investigators found high rates of adverse events in both groups.
At 3 months after the initial injection, 15% of patients in the placebo group and 20% of patients in the treatment group had undergone amputation. The overall MALE rate was 9% in the placebo group and 14% in the treatment group. Additionally, 21% of those in the placebo group and 30% of those in the treatment group saw their wounds grow by 25% or more during the 3-month follow-up. Differences in the rates of these outcomes were not statistically significant between groups.
Dr. Shishehbor noted that a unique aspect of the study was its close assessment of blood flow in the smaller arteries at baseline and during follow-up using TBI. Despite undergoing extensive revascularization to improve blood flow, none of the patients achieved a normal TBI (> 0.71) after revascularization or at 3 months. There was no significant difference in TBI at 3 months between the treatment and placebo groups.
In the ACC press release, Dr. Shishehbor commented, "These results clearly highlight the need for identifying additional therapies, or perhaps combinations of therapies, that could help these patients. The fact that only about 25% of these patients had healed at 3 months, despite being in a very rigorous, highly monitored environment both from the standpoint of wound healing and revascularization, makes us even more motivated to continue to seek additional therapies."
He added, "We are very much looking forward to the 6-month data. Based on those results, we will determine whether we will investigate this biologic therapy in a longer study, or perhaps consider studying a combination therapy that involves more than one biologic therapy."