Safety and Efficacy Assessment of HAV in Patients Needing Vascular Access for Dialysis

This is a Phase 2, prospective, multicenter, open-label, single-arm study. Subjects who sign informed consent would undergo study-specific screening assessments within 45 days from the day of informed consent.

Eligible study subjects will receive a HAV and will be followed to 12 months post-implantation at routine study visits regardless of patency status. After 12 months, subjects with a patent HAV will be followed (while the HAV remains patent) for up to 2 years (24 months) post implantation at study visits every 6 months.

Inclusion criteria

• Subjects with ESRD who are not, or who are no longer candidates for creation of an autologous AV fistula and therefore need placement of an AV graft in the arm (upper or forearm) for hemodialysis therapy.
• Already established on hemodialysis
• At least 18 years of age at Screening.
• Suitable arterial and venous anatomy for implantation of straight or looped conduits in either the forearm or upper arm (not crossing the elbow).
• Hemoglobin ≥ 8 g/dL and platelet count ≥ 100,000 cells/mm3 prior to Day 0 (within 45 days).
• Other hematological and biochemical parameters within a range consistent with ESRD prior to Day 0 (within 45 days).
• Normal clotting (international normalized ration [INR] ≤ 1.5 or prothrombin time ≤ 18 sec unless the patient is taking an anticoagulant for an approved indication at the time of HAV implantation.
• Female subjects must be either:

• Of non-childbearing potential, which is defined as post-menopausal (at least 1 year without menses prior to Screening) or documented surgically sterile or post hysterectomy (at least 1 month prior to Screening)
• Or, of childbearing potential, in which case:

i. Must have a negative serum or urine pregnancy test at Screening, and ii. Must agree to use at least one form of the following birth control methods for the duration of the study:

• Established use of oral, injectable or implanted hormonal methods of contraception 2. Placement of an intrauterine device or intrauterine system 3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository 9. Subject, or legal representative, able to communicate effectively with investigative staff, competent and willing to give written informed consent, and able to comply with entire study procedures including all scheduled follow-up visits.

• Life expectancy of at least 1 year.

Exclusion criteria

• History or evidence of severe peripheral vascular disease in the intended arm for implantation.
• Known or suspected central vein stenosis or conduit occlusion on the ipsilateral side of the planned implantation, unless the stenosis is corrected prior to HAV implantation.
• Treatment with any investigational drug or device within 60 days prior to study entry (Day 0) or ongoing participation in a clinical trial of an investigational product.
• Cancer that is actively being treated with a cytotoxic agent.
• Documented hyper-coagulable state as defined as either:

• a biochemical diagnosis (e.g. Factor V Leiden, Protein C deficiency, etc.) - OR -
• a clinical history of thrombophilia as diagnosed by 2 or more spontaneous intravascular thrombotic events (e.g deep vein thrombosis, pulmonary embolism, etc.) within the 5 previous years.
• Spontaneous or unexplained bleeding diathesis clinically documented within the last 5 years or a biochemical diagnosis (e.g. von Willebrand disease, etc.).
• Active clinically significant immune-mediated disease, not controlled by maintenance immunosuppression.

• Low dose glucocorticoid therapy (e.g. up to 10 mg a day prednisone or prednisolone) is acceptable.
• High dose glucocorticoid therapy for treatment of autoimmune flare, or other inflammatory diseases is excluded.
• Patients using glucocorticoids for immunosuppression post-transplant to prevent against transplanted allograft rejection in the period post allograft failure are excluded.
• The following examples of immunosuppressive agents (or the like) are exclusionary for enrollment in this clinical trial:

i. tacrolimus or FK506 [Prograf] ii. mycophenolate mofetil [Cellcept], iii. cyclosporine [Sandimmune or Gengraf] iv. Sirolimus administered systemically (Sirolimus in drug eluting stents is NOT an exclusion)

• Anticipated renal transplant within 6 months.
• Venous outflow from HAV cannot be placed more centrally than the venous outflow of any previous failed access on that extremity.
• Active local or systemic infection (white blood cells [WBC] > 15,000 cells/mm3 at Screening). If the infection resolves, the subject must be at least 1 week post resolution of that infection before implantation.
• Known serious allergy to planned antiplatelet agent.
• Pregnant women, or women intending to become pregnant during the course of the trial.
• Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV.
• Previous enrollment in this study or any other study with HAV.
• Employees of Humacyte and employees or relatives of the investigator.