Clinical trial NCT02956993: Safety/Feasibility of Vonapanitase Following Angioplasty for Patients With Peripheral Artery Disease (PAD) Below the Knee (BTK)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peripheral Artery Disease
Keywords: 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
Lead sponsor: Proteon Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-11-06
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Screening: Initial study inclusion criteria

1. Age of at least 18 years.
2. Clinical diagnosis of PAD secondary to atherosclerosis affecting a lower limb.
3. Rutherford category 3-5.
4. De novo lesion, not previously treated by angioplasty, atherectomy or stenting.
5. Scheduled to undergo angioplasty of the distal popliteal, tibial or peroneal arteries.
6. 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.
7. Ability to understand and comply with the requirements of the entire study and communicate with the study team.
8. 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
9. 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.
10. 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

1. 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).
2. Planned above ankle amputation on ipsilateral limb within 4 weeks of study drug administration.
3. Prior or planned stenting of the target lesion.
4. Deep vein thrombosis within the past 3 months.
5. Known bleeding disorder.
6. Known hypercoagulable state (e.g., protein C deficiency, factor V Leiden, prothrombin G20210A mutation).
7. Platelet count \<130K, hematocrit \<30%, bilirubin or ALT \>3.0 times the upper limit of normal.
8. Renal failure with existing dependence on dialysis or an eGFR by MDRD calculation of \< 20 mL/min/1.73 m2.
9. Pregnancy, lactation or plans to become pregnant during the course of the study.
10. Presence of any significant medical condition that might significantly confound the collection of safety and efficacy data in this study.
11. 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.
12. Treatment with any investigational drug within the previous 30 days or investigational antibody therapy within 90 days prior to signing informed consent.
13. Known allergy to radiocontrast agents.

    Procedure:

    Exclusion criteria to be determined at the time of the angioplasty procedure
14. Reference vessel diameter \< 2 mm and \> 8 mm.
15. Severe concentric medial calcification of the target lesion thought to interfere with study drug delivery to the adventitia based on fluoroscopic appearance.
16. Aneurysm in the target vessel.
17. Failure to cross the target lesion with a guide wire; however subintimal wire crossing is allowed.
18. Stenting of the target lesion.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 6 months following study drug administration
measure: Technical success of perivascular injection
timeFrame: Intraprocedural
Secondary outcomes:
Other outcomes:
measure: Minimum lumen diameter [MLD]
timeFrame: Intraprocedural and 6 months following study drug administration
measure: Minimum lumen area [MLA]
timeFrame: Intraprocedural and 6 months following study drug administration
measure: Incidence of arterial occlusion
timeFrame: 14 days and 6 months following study drug administration
measure: Rutherford category
timeFrame: 14 and 28 days, and 6 months following study drug administration
measure: Ankle-brachial index [ABI]
timeFrame: 14 days and 6 months following study drug administration
measure: Vascular Quality of Life Questionnaire-6 [VascuQol-6
timeFrame: 14 days and 6 months following study drug administration
Locations:
city: Long Beach
country: United States
facility: VA Medical Center Long Beach
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Healthcare System
state: Colorado
city: Gainesville
country: United States
facility: UF Health at the University of Florida
state: Florida
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Steward St. Elizabeth's Medical
state: Massachusetts
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Austin
country: United States
facility: Cardiothoracic and Vascular Surgeons
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: