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

Sponsor

Proteon Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02956993

Collaborator

(none)

Enrollment

Locations

Arms

29.9

Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Artery Disease	Drug: vonapanitase Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2016

Actual Primary Completion Date :

Apr 30, 2019

Actual Study Completion Date :

Apr 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vonapanitase Vonapanitase administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter.	Drug: vonapanitase Other Names: PRT-201
Placebo Comparator: Placebo Placebo administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter.	Drug: Placebo

Arm

Intervention/Treatment

Active Comparator: Vonapanitase

Vonapanitase administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter.

Drug: vonapanitase

Other Names:

PRT-201

Placebo Comparator: Placebo

Placebo administered to the distal popliteal, tibial or peroneal artery using a micro-infusion catheter.

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [Up to 6 months following study drug administration]
Safety assessments include physical exams and routine serum chemistry and hematology tests
Technical success of perivascular injection [Intraprocedural]
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

Other Outcome Measures

Minimum lumen diameter [MLD] [Intraprocedural and 6 months following study drug administration]
Minimum lumen area [MLA] [Intraprocedural and 6 months following study drug administration]
Incidence of arterial occlusion [14 days and 6 months following study drug administration]
Rutherford category [14 and 28 days, and 6 months following study drug administration]
Ankle-brachial index [ABI] [14 days and 6 months following study drug administration]
Vascular Quality of Life Questionnaire-6 [VascuQol-6 [14 days and 6 months following study drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center Long Beach	Long Beach	California	United States	90822
2	VA Eastern Colorado Healthcare System	Denver	Colorado	United States	80220
3	UF Health at the University of Florida	Gainesville	Florida	United States	32610
4	Boston Medical Center	Boston	Massachusetts	United States	02118
5	Steward St. Elizabeth's Medical	Boston	Massachusetts	United States	02135
6	Metro Health Hospital	Wyoming	Michigan	United States	49519
7	Cardiothoracic and Vascular Surgeons	Austin	Texas	United States	78756
8	University of Virginia Health System	Charlottesville	Virginia	United States	22908
9	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226