Study of PVS-10200 for the Treatment of Restenosis in Patients With Peripheral Artery Disease (TRIUMPH)

The purpose of this study is to evaluate the safety of two doses of PVS-10200, an allogeneic cellular therapy, delivered as a single injection following percutaneous transluminal ("balloon") angioplasty and stent placement for the treatment of peripheral artery disease (PAD).

This is an open-label dose escalation safety study of PVS-10200 in 30 subjects with peripheral artery disease (PAD) requiring balloon angioplasty and stent placement in the superficial femoral artery (SFA). The study will be completed sequentially in two dose cohorts of 10 subjects (low dose group, Cohort A) and 20 subjects (high dose group, Cohort B). A Data Safety Monitoring Board (DSMB) will conduct regular safety reviews.

Each subject will receive one treatment of PVS-10200 delivered by ultrasound guided injection to the perivascular region (external to the vessel) of the stented target lesion. The treatment will be administered within 24 hours after balloon angioplasty/stent placement.

Eligibility Criteria:
Inclusion Criteria:

1. The subject has signed the informed consent document and patient information leaflet.
2. Male and female subject ≥ 18 years of age at the time of consent.
3. If female, the subject is (a) at least 1 year post-menopausal, or (b) surgically sterile, or (c) of child-bearing potential, with a negative serum pregnancy test result prior to study enrollment, who agrees to use adequate contraception for 6 months. Adequate contraception is defined as abstinence or a reliable method of birth control (e.g., a hormonal contraceptive, intra-uterine device, implantable or injectable contraceptives (Norplant® or Depo-Provera®), diaphragm, or condom with spermicide).
4. Subject has symptomatic peripheral arterial disease involving the superficial femoral artery, defined as Fontaine Class IIb, III and IV.
5. Meets anatomic requirements based on biplane digital subtraction angiography performed at the time of intervention including:

   * Stenosis of ≥ 50% or occlusion of the superficial femoral artery, and
   * Target lesion length of ≤ 150 mm, and
   * At least one patent (\< 50 % stenosis) tibioperoneal runoff vessel
6. Target lesion is 7-15 cm in length.
7. Subject is expected to stay in the same geographic area for at least 48 weeks.
8. In the opinion of the investigator, the subject is able to understand and is willing to complete the study requirements.
9. Subject is receiving a therapeutic dose of statin therapy (starting minimum of 7 days prior to intervention) and continuing for a minimum of 4 weeks post-intervention.

Exclusion Criteria:

1. Subject has acute limb ischemia.
2. Subject has had prior revascularization of the target lesion.
3. Subject has untreated inflow disease of the ipsilateral pelvic arteries (\> 50% stenosis or occlusion).
4. The target lesion is located within an aneurysm or associated with an aneurysm in the vessel segment either proximal or distal to the target lesion(s).
5. Subject has an unresolved thrombus within the target vessel.
6. Additional percutaneous interventional procedures (cardiac/peripheral) are planned ≤ 30 days following the study procedure.
7. Subject has suffered a hemorrhagic stroke ≤ 6 mo prior to the study procedure.
8. Subject has a history of bleeding diatheses or coagulopathy.
9. Subject is diagnosed with septicemia at the time of the study procedure.
10. Subject is known to be seropositive for HIV.
11. Subject has some other medical illness that may cause the subject to be non-compliant with the protocol.
12. Subject has a known allergy to bovine or porcine products (i.e., heparin).
13. Subject has a known allergy to collagen/gelatin products.
14. Subject has had a severe reaction to contrast media.
15. Subject has a known allergy or intolerance to anti-platelet medication (e.g., acetylsalicylic acid or clopidogrel) or statin therapy.
16. Subject has a history of IV drug use within 6 months prior to screening.
17. Subject has a documented diagnosis of cancer within 2 years (24 months) prior to screening.
18. Subject is a female who is pregnant, breast-feeding, or plans to become pregnant during the study.
19. Subject is currently participating in another investigational drug, biologic or device trial, plans to participate in another investigational drug, biologic or device study during participation in this study, or has completed participation in another investigational drug, biologic or device trial within the last 30 days. Note: Subjects involved in extended follow-up trials for products that are currently commercially available and used as approved are not considered to be participating investigational trials.
20. Subject is a staff member of any of the participating institutions or relative of a staff member.