Safety and Efficacy Assessment of HAV (Manufactured Using Large-scale System) in Patients Needing Vascular Access for Dialysis

Study Overview
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Brief Summary
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This is a Phase 2, prospective, multicenter, open-label, single-arm study of the Human Acellular Vessel (HAV).

Detailed Description
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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 3 years (36 months) post implantation at study visits every 6 months.

Official Title
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A Phase 2 Assessment of Humacyte's Human Acellular Vessel in Patients Needing Vascular Access for Dialysis

Conditions
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Hemodialysis, Renal Failure, End Stage Renal Disease, Vascular Access

Intervention / Treatment
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* Biological: HAV


Participation Criteria
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Eligibility Criteria
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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: 1. 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. 10. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAV<br>The HAV is a tissue-engineered vascular conduit (6mm diameter) for hemodialysis access in patients with end-stage renal disease. HAV for this study will be manufactured using the commercial manufacturing system.It will be implanted in the forearm or upper arm using standard vascular surgical techniques. All subjects will be required to start taking daily aspirin (75 or 325 mg) on Day 1 after surgical implantation of HAV unless they are already taking another antiplatelet agent. If low molecular weight heparin (LMWH) is administered post-operatively, aspirin or other antiplatelet agents should be initiated after stopping LMWH. Subjects who are known to be aspirin-sensitive should take another antiplatelet agent at the discretion of the Principal Investigator. | Biological: HAV<br>* Surgical implantation of the HAV and subsequent use of the implanted vascular conduit for hemodialysis vascular access.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative number of subjects with adverse events indicating possible mechanical failure or weakness of the HAV | Frequency and severity of AEs of each patient will be documented | Up to 3 months post-implantation | 
| Incidence rate of baseline change of panel reactive antibody (PRA) value | Assess changes in the PRA response over the 2 months after graft implantation | 2 months post implantation | 
| Incidence rate of baseline change of anti-HAV IgG value | Determine whether IgG antibodies to the extracellular matrix material are formed in response to implantation of the HAV | 2 months post implantation | 
| Incidence rate of all adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) | Frequency and severity of AEs/SAE/AESI of each patient will be documented. | Up to 3 months post-implantation | 
| Proportion of subjects with primary patency, primary assisted patency and secondary patency |  | 3 months post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative number of subjects with adverse events indicating possible mechanical failure or weakness of the HAV | Frequency and severity of AEs of each patient will be documented | Up to 36 months post-implantation | 
| Incidence rate of baseline change of panel reactive antibody (PRA) value | Assess changes in the PRA response over the 12 months after graft implantation | 12 months post-implantation | 
| Incidence rate of baseline change of anti-HAV IgG value | Determine whether IgG antibodies to the extracellular matrix material are formed in response to implantation of the HAV | 12 months post-implantation | 
| Incidence rate of all AEs/SAEs | Frequency and severity of AEs/SAE of each patient will be documented | Up to 12 months post-implantation | 
| Incidence rate of SAEs related to the HAV and adverse events of special interest | Frequency and severity of SAE/AESI of each patient will be documented | Up to 36 months post-implantation | 
| Proportion of subjects with primary patency, primary assisted patency and secondary patency |  | Up to 36 months post-implantation | 
| Histopathological remodeling of any study conduit | Microscopic examination of explanted conduit for cellular infiltration and extracellular remodeling processes, including neo-synthesis and reorganization of ECM components (descriptive summaries only) | Up to 36 months post-implantation |