ACP-01 in Patients With Critical Limb Ischemia

The primary objective of this study is to determine the efficacy and safety of intramuscular injection of ACP-01, comprised of blood-derived autologous ACPs, in subjects with critical limb ischemia who are receiving standard of care therapy and have no endovascular or surgical revascularization options.

This prospective, randomized, double-blind, placebo controlled study will assess the efficacy and safety of autologous ACPs administered intramuscularly into the lower extremity of subjects with CLI who lack surgical or endovascular revascularization options.

A total of approximately 95 subjects will be randomized to treatment with ACP-01 or placebo using a 2:1 randomization scheme, respectively, stratified by site.

The study will continue until all subjects treated experience the study event (either de novo gangrene, doubling of wound size, major amputation, or death) or are event-free for at least 26 weeks. Subjects treated will be followed for no longer than 52 weeks.

One futility analysis for potentially stopping study enrollment will be performed.

Subjects treated at each investigative site will provide written informed consent prior to the conduct of any study-related procedures. Thereafter, they will be screened and those meeting the inclusion/exclusion criteria will be enrolled into the trial and undergo all the study procedures including intramuscular injection of the investigational medicinal product (IMP = ACP-01 or placebo). The IMP will be administered in addition to any conventional treatment the subject is receiving.

The control group will receive placebo injections into the lower extremity to ensure blinding of the assessors and the subjects.

The placebo will consist of the same medium used in the ACP product suspension.

The study consists of four periods: Screening period, Treatment period, Acute safety follow-up and Long term follow-up periods. The total duration of study participation, including follow-up, is at least 26 weeks. Subjects will be followed for up to 52 weeks and at least until the last subject has completed his/her 26 week visit.

Eligibility Criteria:
Inclusion Criteria:

* Subject is diagnosed with critical limb ischemia.
* Subject has hemodynamic indicators of severe peripheral arterial occlusive disease.
* Subject is not a candidate for standard revascularization treatment options for peripheral arterial disease.
* Subject must be on standard of care medical therapy for peripheral vascular disease.
* Male or female age 18 and above.
* Non-pregnant, non-lactating female.
* Subject is able to understand and provide voluntary signed informed consent.

Exclusion Criteria:

* Uncorrected aorto-iliac occlusive disease.
* Subjects who, in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation in a time frame shortly after administration of the IMP (investigational drug or placebo).
* Advanced Critical Limb Ischemia (CLI) presenting as severe ischemic or dry gangrene.
* Lower extremity non-treated active infection.
* Hypercoagulable state.
* Subject received a blood transfusion during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood).
* Inability to communicate that may interfere with clinical evaluation.
* Recent major non-vascular operation.
* Myocardial infarction or uncontrolled myocardial ischemia or persistent severe heart failure.
* Severe aortic stenosis.
* Renal failure.
* Hepatic failure.
* Anemia.
* Major stroke.
* Diagnosis of malignancy.
* Concurrent chronic or acute infectious disease and uncontrolled infectious symptoms.
* Severe concurrent disease (other than Peripheral Vascular Disease (PAD)).
* Bleeding diathesis.
* Participation at the same time in another investigational product or device study.
* Chronic cytotoxic drug treatment.
* Life expectancy of less than 6 months.
* Subject unlikely to be available for follow-up.
* Acute worsening of CLI.