This will be a randomized, placebo-controlled, parallel group, multicenter, Phase III study.The study aims to evaluate the Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects with Critical Limb Ischemia (CLI) with Minor Tissue Loss (Rutherford Category 5) who are Unsuitable for Revascularization.
- Subjects with a diagnosis of peripheral artery disease (PAD) due to arterosclerosis at the stage of CLI, with minor tissue loss up to the trans-metatarsal level (Rutherford Category f) (black toe due to CLI is acceptable if not infected).
- Ankle pressure (AP) =< 70 mmHg or toe pressure (TP) =< 50 mmHg in the index leg. If a unfavorable risk-benefi assessment of a multidisciplanary team including a vascular surgeon and an interventionalist/endovascular specialist (who might be a vascular surgeon, angiologist/cardiologist/internist, interventional radiologist), and, if relevant, an anesthesiologist (unsuitability to revascularization should be based on anatomic considerations, technical considerations, or subject's comorbidities as detailed in protocol section 1.7).
- Ischemic wounds in the index leg stable for at least 2 weeks during the screening period defined as no change of more than 20% in wound area in either direction, in each ischemic wound.
- Non-artherosclerotic peripheral artery disease.
- CLI with major tissue loss (Rutherford Category 6) in either leg.
- Evidence of active infection in either leg. If there is clinical suspicion of osteomyelitis, imaging per local medical practice should be performed, and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) should be assessed. If the subject had osteomyelitis within the last 3 months, recovery should be confirmed by imaging and by ESR or CRP normalization.
Experimental: PLX-PAD will be administered via 30 local IM injections (0.5 mL each). Each subject will be treated twice, with an interval of 8 weeks between treatments.
Placebo: Placebo will be administered via 30 local IM injections (0.5 mL each). Each subject will be treated twice, with an interval of 8 weeks between treatments.
Screening period of up to 5 weeks. All subjects will be followed-up until the End of STudy or until completing 36 months of follow-up - the earlier of the two.
Study visits will be conducted every month up to month 6, then every 3 months until month 12, and for subjects followed more than 12 months every 4 months until the subject's Termination Visit.