safety and efficacy of allogeneic cells for the treatment of intermittent claudication(ic)

Conditions: Intermittent Claudication; Peripheral Artery Disease

Summary: the objective of the study is to establish the safety profile of intramuscular plx-pad injections and to evaluate the clinical efficacy of it in ic subjects comprising of 4 treatment groups: 1. double treatment of plx-pad low dose 2. double treatment of plx-pad high dose 3. double treatment of placebo 4. single treatment of plx-pad high dose and additional treatment of placebo. subjects will receive the assigned treatment twice to the affected leg, within 12-weeks interval between each treatment. the study will be comprised of 5 stages: screening period of up to 4 weeks,first treatment of plx-pad or placebo followed by additional injection after 12 weeks and with follow-up of 12 months post second injection


Eligibility criteria:
inclusion criteria: * adult male or female subjects between 45 to 85 years of age (inclusive) at the time of screening visit. * subjects with a diagnosis of peripheral artery disease, secondary to atherosclerosis, confirmed by one of the following criteria assessed at the screening visit: * resting ankle-brachial index (abi) ≤ 0.80 or * resting abi ≤ 0.90 and \>20% decrease in abi from rest to exercise when measured within 1 minute after treadmill exercise or * toe-brachial index (tbi) ≤ 0.60 * lifestyle-limiting, moderate to severe claudication (symptoms present and stable for \> 6 months and not significantly changed within the past 3 months prior to screening). * evidence of significant (\>50%) stenosis infra-inguinal occlusive disease as confirmed by documented results from duplex, mra, cta and/or contrast angiogram completed within 3 months prior to screening. * the longest maximal walking distance (mwd) from the screening period exercise treadmill tests (ett), utilizing a modified gardner protocol (appendix i), must be between 1 and 10 minutes (inclusive). * subjects who have persistent claudication symptoms despite having been recommended an exercise program if feasible, and or despite having been on a stable dose of cilostazol, if indicated. subjects should be cilostazol free for at least 2 weeks prior to the first ett. * subjects should be receiving standard of care drugs for vascular disease including anti-platelet agent(s) and statin medication, as well as anti-hypertensive medication(s) and oral hypoglycemic agents/insulin, if indicated. * signed written informed consent. exclusion criteria: * ischemic rest pain; ulceration or gangrene (fontaine class iii-iv; rutherford category 4-6). * failed lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within the prior one month of screening. * planned revascularization (surgical or endovascular intervention) within 12 months after screening. * lower extremity arteries inflow obstruction (defined as a greater than 50% stenosis of aorta, iliac and/or common femoral arteries). * history of buerger's disease. * uncontrolled hypertension (defined as diastolic blood pressure \> 100 mmhg or systolic blood pressure \> 180 mmhg during screening). * uncontrolled diabetes defined as glucose control hba1c \> 9% at screening. * life-threatening ventricular arrhythmia - except in subjects with an implantable cardiac-defibrillator. * serum creatinine level\>2.5mg/dl. * sgpt (alt), sgot (ast) \>2.5 x upper limit of normal range. * hemoglobin \< 10 g/dl. * unstable cardiovascular disease defined as myocardial infarction (stemi or nstemi) within 3 months prior to screening, or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged episodes. * transient ischemic attack (tia)/stroke within 3 months prior to screening. * subjects with severe congestive heart failure symptoms (i.e. nyha stage iii to iv). * subjects with implant of mechanical prosthetic heart valve(s). * pulmonary disease requiring supplemental oxygen treatment on a daily basis. * severe, active infection of the involved extremity(ies), including osteomyelitis, fasciitis, or severe/purulent cellulitis. * history of malignancy within 5 years prior screening requiring chemotherapy and/or radiotherapy and/or immunotherapy, excluding basal or squamous cell carcinoma of the skin. * exercise is limited by any condition other than ic, including but not limited to congestive heart failure, chronic pulmonary disease, angina pectoris, or degenerative joint disease. * uninterrupted use of warfarin or non-steroidal anti-inflammatory agents (with the exception of ibuprofen at doses up to 1,200 mg/day or diclofenac at dose of 75mg/day). * subjects who are on oral anticoagulant therapy (warfarin, dabigatran, apixaban, endoxaban and rivaroxaban). unless, upon primary care physician and/or investigator's discretion the subjects who are on warfarin treatment can switch to low molecular weight heparin treatment (such as: clexane) 5-7 days prior study treatment administration and return to warfarin treatment 24 hours post study treatment administration. * subjects who are taking immunosuppressive treatment (including high dose steroids). * known allergies to protein products (bovine serum, or recombinant trypsin) used in the cell production process. * known sensitivity to gentamycin. * known sensitivity to antihistamine drugs. * history of hospitalization due to allergic/hypersensitivity reaction to any substance (e.g. food or drug). * medical history of human immunodeficiency virus (hiv) or syphilis positivity at time of screening. * known active hepatitis b, or hepatitis c infection at the time of screening. * pregnant or breast-feeding women or women of childbearing age not protected by an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide). * in the opinion of the investigator, the subject is unsuitable for participating in the study. * subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s). * subjects that have prior exposure to gene or cell based therapy. * subjects who are legally detained in an official institute.