Safety/Feasibility of Vonapanitase Following Angioplasty for Patients With Peripheral Artery Disease (PAD) Below the Knee (BTK)

Study Overview
=================
Brief Summary
-----------------
The research study is designed to assess the technical feasibility and safety of a perivascular injection of vonapanitase delivered via micro-infusion catheter to the distal popliteal, tibial or peroneal arteries immediately following successful angioplasty.

Official Title
-----------------
A Phase 1, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Vonapanitase Administered Following Angioplasty of a Distal Popliteal, Tibial or Peroneal Artery in Patients With Peripheral Artery Disease

Conditions
-----------------
Peripheral Artery Disease

Intervention / Treatment
-----------------
* Drug: vonapanitase
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Screening: Initial study inclusion criteria Age of at least 18 years. Clinical diagnosis of PAD secondary to atherosclerosis affecting a lower limb. Rutherford category 3-5. De novo lesion, not previously treated by angioplasty, atherectomy or stenting. Scheduled to undergo angioplasty of the distal popliteal, tibial or peroneal arteries. If female and of childbearing potential (premenopausal and not surgically sterile) must have a negative pregnancy test at the screening visit and be willing to use contraception from the time of the screening visit to 1 week following study drug administration. Acceptable methods of birth control include abstinence, barrier methods with spermicide, implants, injectables, oral contraceptives, intra-uterine device, or a vasectomized partner. Ability to understand and comply with the requirements of the entire study and communicate with the study team. Ability to provide written informed consent using a document that has been approved by the required institutional review board. Procedure: Study inclusion criteria to be determined at the time of the angioplasty procedure Atherosclerotic lesion with >50% stenosis in the popliteal (distal to the center of the knee joint space, the P3 segment), tibial or peroneal artery prior to angioplasty. Successful revascularization without the use of stenting of the target lesion; no flow limiting dissection and <30% residual lumen stenosis as compared with an adjacent non-diseased lumen diameter. Exclusion Criteria Screening: Initial study exclusion criteria Patients in whom arterial insufficiency in the lower extremity is the result of an immunologic or inflammatory non-atherosclerotic disorder (e.g., Buerger's disease, vasculitis). Planned above ankle amputation on ipsilateral limb within 4 weeks of study drug administration. Prior or planned stenting of the target lesion. Deep vein thrombosis within the past 3 months. Known bleeding disorder. Known hypercoagulable state (e.g., protein C deficiency, factor V Leiden, prothrombin G20210A mutation). Platelet count <130K, hematocrit <30%, bilirubin or ALT >3.0 times the upper limit of normal. Renal failure with existing dependence on dialysis or an eGFR by MDRD calculation of < 20 mL/min/1.73 m2. Pregnancy, lactation or plans to become pregnant during the course of the study. Presence of any significant medical condition that might significantly confound the collection of safety and efficacy data in this study. Malignancy or treatment for malignancy within the previous 12 months with the exception of localized basal cell or squamous cell skin cancer, or any cancer in situ. Treatment with any investigational drug within the previous 30 days or investigational antibody therapy within 90 days prior to signing informed consent. Known allergy to radiocontrast agents. Procedure: Exclusion criteria to be determined at the time of the angioplasty procedure Reference vessel diameter < 2 mm and > 8 mm. Severe concentric medial calcification of the target lesion thought to interfere with study drug delivery to the adventitia based on fluoroscopic appearance. Aneurysm in the target vessel. Failure to cross the target lesion with a guide wire; however subintimal wire crossing is allowed. Stenting of the target lesion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vonapanitase<br>Vonapanitase administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter. | Drug: vonapanitase<br> <br> * Other names: PRT-201;|
| Placebo Comparator: Placebo<br>Placebo administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter. | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Safety assessments include physical exams and routine serum chemistry and hematology tests | Up to 6 months following study drug administration | 
| Technical success of perivascular injection | Technical success of study drug administration will be assessed by the extent of circumferential and longitudinal coverage of the artery using a protocol-defined assessment scale | Intraprocedural | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
peripheral artery disease, PAD, vonapanitase, critical limb ischemia, CLI, tibial artery, stenosis, distal popliteal artery, peroneal artery, below the knee, BTK, elastase, chymotrypsin-like elastase 1, CELA1, PRT-201