To Compare the Efficacy and Safety of the ATEV With AVF in Female Patients With End-Stage Renal Disease Requiring Hemodialysis

A Phase 3 Randomized Study to Compare the Efficacy and Safety of the Humacyte Acellular Tissue Engineered Vessel (ATEV) With That of an Autogenous Arteriovenous Fistula (AVF) in Female Patients With End-Stage Renal Disease Requiring Hemodialysis

The goal of this clinical trial is to compare the number of catheter-free days (CFD) and the rate and severity of any dialysis access-related infections between the ATEV and AVF groups over 12 months in patients with end-stage renal disease (ESRD) needing hemodialysis (HD).

Participants will be stratified by location of the vascular access (forearm versus upper arm) and by type of AVF creation procedure planned by the surgeon at randomization (1-stage AVF versus 2-stage AVF). The comparator is an upper extremity arterio-venous fistula (AVF) for HD access surgically created per the institution's Standard of Care (SoC).

This is a prospective, multicenter, randomized, two-arm, comparative Phase 3 study of female patients with ESRD, who are receiving clinically successful hemodialysis (HD) via a central venous dialysis catheter (DC).

Approximately 150 female patients will be randomized 1:1 to either the ATEV or the AVF treatment arm. Patients will be stratified by location of the vascular access (forearm versus upper arm) and by type of AVF creation procedure planned by the surgeon at randomization (1-stage AVF versus 2-stage AVF).

All patients will be followed through Month 12 regardless of SA patency status. Patients who have a patent SA at Month 12 will then be followed in the Long-Term Extension study for an additional 12 months with evaluation of exploratory long-term endpoints.

Inclusion Criteria:

1. Female patients with ESRD, currently receiving hemodialysis via dialysis catheter and who are candidates for the creation of an AVF (see Inclusion Criterion #4 below) or implantation of an ATEV for HD access.

2. Patients who plan to undergo HD at a dialysis unit of a participating dialysis provider for at least 12 months after SA creation.

3. Patients aged ≥ 18 years at Screening.

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

   NOTE: Suitable anatomy will be determined by both physical examination and ultrasound imaging or vessel imaging modality in addition to consideration of all vascular sites available, prior access failure, future access sites and possibilities to preserve patients' future alternate accesses. Vessel mapping is the preferred method to assess the vascular anatomy, and will evaluate the following attributes during Screening:

   • Vein diameter
   • Arterial diameter
   • Presence of arterial calcification
   • Depth of the intended fistula conduit from the surface of the skin
   • Central vein patency
   • Previous vascular access location The ultimate decision of anatomic suitability belongs to the surgeon and/or the investigator.

5. Hemoglobin ≥ 7 g/dL and platelet count ≥ 100,000 /mm3

6. Patients must either:

   1. Be of non-childbearing potential, which is defined as post-menopausal (at least 1 year without menses prior to Screening) or documented surgically sterile (i.e., total hysterectomy or tubal ligation, or complete bilateral oophorectomy) at least 1 month prior to Screening.
   2. Or, if of childbearing potential:

   Must have a negative serum pregnancy test at Screening, and

   Must agree to use at least one form of the following birth control methods for the duration of the study:

   i. Established use of oral, injectable or implanted hormonal methods of contraception.

   ii. Placement of an intrauterine device or intrauterine system at least 5 days prior to Screening.

   iii. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/ gel/ film/ cream/ suppository.

7. Patient or their legal representative can communicate effectively with investigative staff, is competent and willing to give written informed consent, and able to comply with entire study procedures including all scheduled follow-up visits.

8. Life expectancy of at least 1 year confirmed by Charlson Comorbidity Index ≤ 9.

Exclusion Criteria:

1. Male sex at birth.

2. Planned AVF creation by means other than suture or vascular anastomotic clips (e.g., endovascular surgery or other anastomotic creation devices). Venous outflow from study access cannot be located more distally than the venous outflow of any previous failed access in that extremity.

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

4. Pregnancy, or women intending to become pregnant during the course of the trial.

5. Treatment with any investigational drug or device within 60 days or 5 half-lives after taking the last dose (whichever is longer) prior to study entry (Day 1) or ongoing participation in a clinical trial of an investigational product.

6. Documented hyper-coagulable state, as defined as either:

   1. Documented hyper-coagulable state, as defined as either: A biochemical diagnosis (e.g., Factor V Leiden, Protein C deficiency, etc.) - OR -
   2. A clinical history of thrombophilia as diagnosed by 2 or more spontaneous intravascular thrombotic events (e.g., deep vein thrombosis (DVT), pulmonary embolism (PE), etc.) within the previous 5 years.

7. Spontaneous or unexplained bleeding diathesis clinically documented within the last 5 years or a biochemical diagnosis (e.g., von Willebrand's disease, etc.).

8. Cancer actively being treated with a cytotoxic agent.

9. Planned or anticipated renal transplant within 6 months after randomization.

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

11. Previous exposure to ATEV.

12. Any of the following within 8 weeks prior to screening: acute coronary syndrome, stroke or congestive heart failure NYHA Stage IV

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