Evaluation of the Safety and Efficacy of a Vascular Prosthesis as an Above-Knee Bypass Graft in Patients With PAD

A Pilot Study for Evaluation of the Safety and Efficacy of Humacyte's Human Acellular Vascular Graft as an Above-Knee Femoro-Popliteal Bypass Graft in Patients With Peripheral Arterial Disease

The purpose of this study is to assess the safety and efficacy of a novel, tissue-engineered vascular prosthesis, the Human Acellular Vessel (HAV).

The HAV is intended as an alternative to synthetic materials and to autologous grafts in the creation of an above-knee femoro-popliteal bypass graft in patients with peripheral arterial disease.

The HAV is a sterile, non-pyrogenic, acellular tubular graft composed of human collagens and other natural extra-cellular matrix proteins. Upon implantation, it is anticipated (based on pre-clinical studies) that the collagen-based matrix comprising the graft will be infiltrated with host cells and re-modeled by the host. This will result in a vascular structure more similar to the histological composition of the native vascular tissue that may improve graft longevity and be less likely to become infected.

Inclusion Criteria:

• Patients with symptomatic peripheral arterial disease who require above knee femoro-popliteal bypass surgery
• Claudication distance of 200 m or less or rest pain or critical limb ischemia
• Preoperative angiography or angio-CT shows superficial femoral artery occlusion of >10 cm AND graft length required ≤ 30 cm. This imaging may have been conducted up to 3 months prior to study entry provided that the patient's symptoms have remained stable since that time
• Preoperative imaging shows at least two below knee vessels patent to the ankle with good runoff
• Femoral artery occlusion is not considered suitable for endovascular treatment
• Autologous vein grafts are not suitable or feasible e.g. because of severe venous disease or prior use of leg veins for other bypass surgery or there is a clinical need to preserve those veins for future bypass surgery in the coronary or peripheral circulation
• Aged 18 to 80 years old, inclusive
• Hemoglobin ≥ 10 g/dL and platelet count ≥ 100,000/mm3 prior to Day 1
• Other hematological and biochemical parameters within a range considered acceptable for the administration of general anesthesia prior to Day 1
• Adequate liver function, defined as serum bilirubin ≤ 1.5 mg/dL; GGT, AST, ALT, and alkaline phosphatase ≤ 2x upper limit of normal or INR ≤ 1.5 prior to Day 1.
• Able to communicate meaningfully with investigative staff, competent to give written informed consent, and able to comply with entire study procedures
• Able and willing to give informed consent
• Life expectancy of at least 2 years

Exclusion Criteria:

• History or evidence of severe cardiac disease (NYHA Functional Class III or IV), myocardial infarction within six months prior to study entry (Day 1), ventricular tachyarrhythmias requiring continuing treatment, or unstable angina
• Acute injury or active infection (including positive cultures of pathogenic bacteria) in the limb receiving the graft
• Stroke within six (6) months prior to study entry (Day 1)
• Treatment with any investigational drug or device within 60 days prior to study entry (Day 1)
• Women of child bearing potential
• Active diagnosis of cancer within the previous year
• Immunodeficiency including AIDS / HIV
• Documented hypercoagulable state or history of 2 or more DVTs or other spontaneous intravascular thrombotic events
• Bleeding diathesis
• Ongoing treatment with vitamin K antagonists or direct thrombin inhibitors or factor Xa inhibitors (e.g. dabigatran, apixaban or rivaroxaban)
• Previous arterial bypass surgery (autologous vein or synthetic graft) in the operative limb
• Previous angioplasty with stenting in the operative limb unless the graft anastomoses can be made at least 1cm distant from the site of the stent
• Stenosis of >50% of the external iliac artery unless it is planned to treat this stenosis with angioplasty with or without stenting prior to, or at the time of, graft implantation
• Distal graft anastomosis likely to be below the knee
• Active autoimmune disease - symptomatic or requiring ongoing drug therapy
• Active local or systemic infection (WBC > 15,000/mm3)
• Known serious allergy to aspirin or penicillin
• Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAVG
• Previous enrollment in this study
• Employees of the sponsor or patients who are employees or relatives of the investigator