SDF1 Plasmid Treatment for Patients With Peripheral Artery Disease

Study Overview
=================
Brief Summary
-----------------
To investigate the efficacy of the administration of JVS-100 delivered via direct intramuscular injections on a 3 month and 6 month composite endpoint of wound progression, healing and limb loss in patients with severe peripheral arterial disease with non-healing chronic wounds who undergo an open bypass grafting or endovascular procedure for treatment of infrapopliteal disease and are dosed within 12 days and 3 months following the procedure.

Official Title
-----------------
A Phase 2B Randomized Double Blind Placebo Controlled Study to Evaluate the Safety and Efficacy of JVS-100 Administered by Direct Intramuscular Injection as Adjunct to Revascularization of Infrapopliteal Lesions in Subjects With Advanced Peripheral Artery Disease and Tissue Loss

Conditions
-----------------
Peripheral Arterial Disease

Intervention / Treatment
-----------------
* Biological: JVS-100
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Major Inclusion Criteria: Age ≥18 Currently receiving standard of care wound treatment (>2 weeks) for chronic wounds or gangrene including as indicated: debridement, pressure offloading, infection control, and/or maintenance of a moist wound environment. Diagnosis of advanced PAD with tissue loss (ulceration and/or dry gangrene) on the foot of the index leg with an ulcer size of at least 0.5 cm2 and <25 cm2. Index wounds on the heel must be <10 cm2 that cannot be probed to bone, have exposed bone or osteomyelitis. Post revascularization intervention inclusion criteria include an attempt at open bypass grafting or endovascular intervention of a popliteal/infrapopliteal lesion(s) on the same leg that has tissue loss without significant improvement in TBI post intervention. The following will be accepted as demonstrating a lack of post intervention toe brachial index (TBI) improvement: TBI ≤ 0.51or; Toe pressure ≤50 mmHg with flat or dampened wave forms or; Skin Perfusion pressure ≤40 mmHg at mid foot level or; TcPO2 ≤40 mmHg Subjects willing to forgo treatment with hyperbaric oxygen, nerve stimulation or sympathectomy for the treatment of advanced PAD from time of consent to 6 months following the initial injection of study drug Major Exclusion Criteria: Previous major amputation of the leg to be treated or planned major amputation or transmetatarsal amputation within the first month following enrollment. Only a short segment superficial femoral artery lesion - consistent with Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) A or B category, and no infrapopliteal disease Staged or planned intervention in the index leg within 30 days after the index procedure Acute limb-threatening ischemia, trauma, known non-atherosclerotic vascular disease Non-salvageable limb defined as major tissue loss and an unsalvageable foot; Wounds that have decreased in size by >50% between the Screening visit and Day 0. If patient has active infection of the index limb that is being treated, and, in the opinion of treating physician, will not lead to an amputation within the next 3 months, the patient can be enrolled. Inability to safely perform a revascularization procedure due to uncontrolled diabetes or other medical condition. Presence of any other condition that, in the opinion of the investigator, might compromise any aspect of the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 8 mg JVS-100<br>Biological/Vaccine: JVS-100 Injection Intramuscular Injection | Biological: JVS-100<br>* Biological/Vaccine: JVS-100 Intramuscular Injection<br>|
| Placebo Comparator: 8 mg placebo<br>Biological/Vaccine: Placebo Injection Intramuscular Injection | Biological: Placebo<br>* Biological/Vaccine: Placebo Intramuscular Injection<br>|
| Active Comparator: 16 mg JVS-100<br>Biological/Vaccine: JVS-100 Injection Intramuscular Injection | Biological: JVS-100<br>* Biological/Vaccine: JVS-100 Intramuscular Injection<br>|
| Placebo Comparator: 16 mg placebo<br>Biological/Vaccine: Placebo Injection Intramuscular Injection | Biological: Placebo<br>* Biological/Vaccine: Placebo Intramuscular Injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite is designed to quantify clinically significant improvement or worsening over baseline by assigning a score to each patient that represents their overall outcome. | Change from baseline in the composite endpoint at 3 months in all treated (or one JVS-100 dose group) compared to all placebo. | 3 months | 
| The composite is designed to quantify clinically significant improvement or worsening over baseline by assigning a score to each patient that represents their overall outcome. | Change from baseline in the composite endpoint at 6 months in all treated (or one JVS-100 dose group) compared to all placebo. | 6 months |