Comparison of the Human Acellular Vessel (HAV) With Fistulas as Conduits for Hemodialysis

A Phase 3 Study to Compare the Efficacy and Safety of Humacyte's Human Acellular Vessel With That of an Autologous Arteriovenous Fistula in Subjects With End Stage Renal Disease

The main purpose of this study is to compare the Human Acellular Vessel (HAV) with arteriovenous fistula (AVF) when used for hemodialysis access

This is a Phase 3, prospective, multicenter, open-label, randomized, two-arm, comparative study. Subjects who sign informed consent will undergo study-specific screening assessments within 45 days from the day of informed consent.

Eligible study subjects will be randomized to receive either an HAV or AVF. The randomization will be stratified by upper arm or forearm placement based on the investigator's determination of where the study access (SA) should be located. Subjects will be followed to 24 months post SA creation at routine study visits regardless of patency status. After 24 months, AVF subjects with a patent SA will be followed (while the SA remains patent) for up to 5 years (60 months) post SA creation at routine study visits. After 24 months, HAV subjects will be followed (regardless of SA patency) for 5 years (60 months) post SA creation at routine study visits.

Inclusion Criteria:

1. Subjects with end-stage renal disease (ESRD), receiving HD via DC and are suitable for the creation of an AVF or implantation of AVG for HD access.

2. Subjects who plan to undergo HD at a dialysis unit of a participating dialysis provider for at least the first 6 months after SA creation.

3. Subjects aged at least 18 years at Screening.

4. Suitable anatomy for creation of a forearm or upper arm AVF and for implantation of straight or looped HAV in either the forearm or upper arm.

5. Hemoglobin ≥8 g/dL and platelet count ≥100,000 /mm3.

6. International Normalized Ratio (INR) ≤ 1.5.

7. Female subjects must be either:

   1. 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).
   2. Or, of childbearing potential, in which case:

   i. Must have a negative urine or serum 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.
   • Placement of an intrauterine device or intrauterine system.
   • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/ gel/ film/ cream/ suppository.

8. 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.

9. Life expectancy of at least 2 years.

Exclusion Criteria:

1. Subjects who are optimal candidates for radiocephalic AVF as indicated by meeting ALL of the following criteria:

   1. No previous failed AVF.
   2. Cephalic vein diameter on ultrasound of more than 3.5mm.
   3. Radial artery diameter on ultrasound of more than 3mm.
   4. Vein depth of less than 0.5cm from the skin.
   5. Normal Allen's test indicating that ulnar artery flow to the hand is sufficient.
   6. No calcification in the wall of the distal radial artery.
   7. Sufficient length of the proposed fistula outflow vein to provide an adequate (at least 6 cm) cannulation segment.
   8. No evidence of iatrogenic injury to target artery or vein.

2. Uncontrolled diabetes;

   a. HbA1c >10% (at Screening).

3. History or evidence of severe peripheral arterial disease in the extremity selected for implant.

4. Known or suspected central vein stenosis or obstruction on the side of planned SA creation, unless corrected prior to randomization.

5. Planned AVF creation that requires more than one stage to complete. (e.g. basilic vein transposition AVF performed in 2 stages).

6. Planned AVF creation by means other than suture or vascular anastomotic clips (e.g. endovascular surgery or other anastomotic creation devices).

7. 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.

8. Cancer that is actively being treated with a cytotoxic agent.

9. Documented hyper-coagulable state.

10. Bleeding diathesis.

11. Active clinically significant immune-mediated disease, not controlled by maintenance immunosuppression.

    1. Low dose glucocorticoid therapy (e.g. 5-10mg prednisone [Deltason]) is acceptable.

    2. High dose glucocorticoid therapy for treatment of autoimmune flare, or other inflammatory diseases is excluded.

    3. Patients using glucocorticoids for immunosuppression post-transplant to prevent against transplanted allograft rejection in the period post allograft failure are excluded.

    4. The following examples of immunosuppressive agents (or the like) are exclusionary for enrollment in this clinical trial:

       • tacrolimus or FK506 [Prograf]
       • mycophenolate mofetil [Cellcept],
       • cyclosporine [Sandimmune or Gengraf]
       • sirolimus [Rapamune] (this only includes systemically administered, drug eluting stents are acceptable)

12. Anticipated renal transplant within 6 months.

13. History of heparin-induced thrombocytopenia.

14. Venous outflow from SA cannot be located more centrally than the venous outflow of any previous failed access in that extremity.

15. 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 one week post resolution of that infection before SA creation.

16. Known serious allergy or intolerance to aspirin and alternative antiplatelet therapy.

17. Pregnant women, or women intending to become pregnant during the course of the trial.

18. Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the SA.

19. Previous enrollment in this study or any other study with HAV.

20. Employees of Humacyte and employees or relatives of an investigator.