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

Peripheral Artery Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02956993
• Other study ID #: PRT-201-115
• Status: Completed
• Phase: Phase 1
• Start date: November 2016
• Est. completion date: April 30, 2019

Study information

• Verified date: April 2019
• Source: Proteon Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Artery Disease

Intervention

Drug:
• vonapanitase

• Placebo

Locations

Country	Name	City	State
United States	Cardiothoracic and Vascular Surgeons	Austin	Texas
United States	Boston Medical Center	Boston	Massachusetts
United States	Steward St. Elizabeth's Medical	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	VA Eastern Colorado Healthcare System	Denver	Colorado
United States	UF Health at the University of Florida	Gainesville	Florida
United States	VA Medical Center Long Beach	Long Beach	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Proteon Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimum lumen diameter [MLD]		Intraprocedural and 6 months following study drug administration
Other	Minimum lumen area [MLA]		Intraprocedural and 6 months following study drug administration
Other	Incidence of arterial occlusion		14 days and 6 months following study drug administration
Other	Rutherford category		14 and 28 days, and 6 months following study drug administration
Other	Ankle-brachial index [ABI]		14 days and 6 months following study drug administration
Other	Vascular Quality of Life Questionnaire-6 [VascuQol-6		14 days and 6 months following study drug administration
Primary	Incidence of adverse events	Safety assessments include physical exams and routine serum chemistry and hematology tests	Up to 6 months following study drug administration
Primary	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