PLX-PAD Cell Treatment of Critical Limb Ischaemia: Rationale and Design of the PACE Trial

Background:
Critical limb ischemia (CLI) is a life threatening condition with a considerable risk for death and major amputation. Besides revascularization, no treatment has been proven to reduce the risks. Therapeutic angiogenesis by gene or cell therapy has not demonstrated definitive evidence in randomized controlled trials. PLX-PAD is an ‘off-the-shelf’ allogeneic placental derived, mesenchymal-like cell therapy that in preclinical studies has shown pro-angiogenic, anti-inflammatory and regenerative properties. Favorable 1-year amputation free survival (AFS), and trends in reduction of pain scores and in increase of tissue perfusion have been shown in two small, open-label, phase I trials.

Study design:
The PACE study is a phase III randomized, double-blind, multicenter, multinational placebo-controlled, parallel-group study to evaluate the efficacy, tolerability and safety of intramuscular injections of PLX-PAD cells to treat patients with atherosclerotic CLI with minor tissue loss (Rutherford Category 5) up to the ankle level, who are unsuitable for revascularization or carry an unfavorable risk-benefit for that treatment. The study will enroll 246 patients, who after screening are randomized in a ratio of 2:1 to treatment with intramuscular injections of PLX-PAD 300X106 cells or placebo at two occasions, 8 weeks apart. The primary efficacy endpoint is time to major amputation or death (amputation free survival), which will be assessed in follow-up of after at least 12 months and up to 36 months.

Conclusions:
Based on favorable pre-clinical and initial clinical study results, the PACE phase III randomized controlled trial will evaluate placenta-derived PLX-PAD cell treatment in patients with critical limb ischemia, carrying an unfavorable risk-benefit for revascularization.