Cellular therapy with Ixmyelocel-T to treat critical limb ischemia: the randomized, double-blind, placebo-controlled RESTORE-CLI trial

Abstract

Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in patients with lower extremity critical limb ischemia (CLI) with no options for revascularization. This randomized, double-blind, placebo-controlled, phase 2 trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections of ixmyelocel-T with placebo. Patients received one-time injections over 20 locations in a single leg and were followed for 12 months. Safety assessments included occurrence of adverse events. Efficacy assessments included time to first occurrence of treatment failure (TTF; major amputation of injected leg; all-cause mortality; doubling of total wound surface area from baseline; de novo gangrene) and amputation-free survival (AFS; major amputation of injected leg; all-cause mortality). A total of 77 patients underwent bone marrow or sham aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24 patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically meaningful 32% reduction in event rate that was not statistically significant (P = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank test). Ixmyelocel-T treatment was well tolerated and may offer a potential new treatment option.

Figure 1

Patient recruitment and disposition throughout the trial. N, number of patients.

Figure 2

Time to first occurrence of treatment failure for all patients injected. Kaplan–Meier survival plot of time to treatment failure (major amputation of injected leg, all-cause mortality, doubling of total wound surface area from baseline, de novo gangrene) for all patients injected. Censored observations are indicated by “+” symbols. CL, confidence limits; NA, not available.

Figure 3

Amputation-free survival for all patients injected. Kaplan–Meier survival plot of amputation-free survival (major amputation of injected leg or all-cause mortality) for all patients injected. Censored observations are indicated by “+” symbols. CL, confidence limits; NA, not available.

Figure 4

Time to first occurrence of treatment failure for all patients who had baseline wounds. Kaplan–Meier survival plot of time to treatment failure (major amputation of injected leg, all-cause mortality, doubling of total wound surface area from baseline, de novo gangrene) for post hoc analysis of patients who had baseline wounds. Censored observations are indicated by “+” symbols. CL, confidence limits; NA, not available.

Figure 5

Amputation-free survival for all patients who had baseline wounds. Kaplan–Meier survival plot of amputation-free survival (major amputation of injected leg or all-cause mortality) for post hoc analysis of patients who had baseline wounds. Censored observations are indicated by “+” symbols. CL, confidence limits; NA, not available.