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

Study Overview
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Brief Summary
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The main purpose of this study is to compare the Human Acellular Vessel (HAV) with ePTFE grafts when used for hemodialysis access.

Detailed Description
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This is a Phase 3, prospective, multicenter, multinational, open-label, randomized, two-arm, comparative study. Subjects who sign informed consent would undergo study-specific screening assessments within 35 days from the day of informed consent. On the day of surgery (Day 0), subjects could still be undergoing screening assessments, such as confirmation of inclusion/exclusion criteria, to determine their eligibility before they are randomized in the study. Eligible study subjects will be randomized to receive either a HAV or one of two commercially available ePTFE grafts and followed to 24 months post-implantation at routine study visits regardless of patency status. After 24 months, subjects with a patent study conduit will be followed (while the study conduit remains patent) for up to 5 years (60 months) post implantation at routine study visits.

Official Title
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An Assessment of Humacyte's Human Acellular Vessel in Patients Needing Renal Replacement Therapy: A Comparison With ePTFE Grafts as Conduits for Hemodialysis (HUMANITY)

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

Intervention / Treatment
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* Biological: Human Acellular Vessel (HAV)
* Device: ePTFE graft


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) to start or maintain hemodialysis therapy. Either on hemodialysis or expected to start hemodialysis within 12 weeks of study conduit implantation. At least 18 years of age at Screening. Suitable 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 35 days). Other hematological and biochemical parameters within a range consistent with ESRD prior to Day 0 (within 35 days). Adequate liver function prior to Day 0 (within 35 days), defined as: ≤2x upper limit of normal (ULN) for serum bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤1.5 for International Normalized Ratio (INR) or prothrombin time (PT) ≤ 18 seconds unless the subject is taking an anticoagulant at the time 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: Must have a negative urine 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: 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 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 obstruction on the side of planned implantation, unless corrected before study conduit 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. Bleeding diathesis. Active clinically significant autoimmune disease. Anticipated renal transplant within 6 months. Venous outflow from study conduit cannot be placed more centrally than any previous failed access. 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 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 study conduit. Previous enrollment in this study or any other study with the 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Acellular Vessel (HAV)<br>The HAV is a tissue-engineered vascular conduit (6mm diameter) for hemodialysis access in patients with end-stage renal disease. It will be surgically implanted in the forearm or upper arm on Study Day 0. | Biological: Human Acellular Vessel (HAV)<br>* Surgical implantation of the HAV and subsequent use of the implanted vascular conduit for hemodialysis vascular access.<br>* Other names: (regulated as a biological product);|
| Active Comparator: ePTFE<br>The comparator (one of two commercially available 6mm ePTFE grafts) will be surgically implanted in the forearm or upper arm on Study Day 0. | Device: ePTFE graft<br>* Surgical implantation of a commercially available ePTFE graft 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 |
| --- | --- | --- |
| Time to loss of Secondary Patency from implantation |  | 18 months post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to loss of Secondary Patency from implantation |  | 12, 24 & 60 months post-implantation | 
| Time to loss of Primary Patency from implantation |  | 12,18, 24, & 60 months post-implantation | 
| Access-related infections | Using Dialysis Event Surveillance Manual: CDC; 2013. | 12, 18, 24, & 60 months post-implantation | 
| Rate of interventions required to achieve/maintain Secondary Patency |  | 12, 18, 24, & 60 months post-implantation | 
| Time to loss of Primary Assisted Patency from implantation |  | 12, 18, 24, & 60 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 60 months post-implantation | 
| The efficiency of dialysis as assessed by spKt/Vurea (subset of subjects) |  | 12, 18 & 24 months post-implantation | 
| Frequency and severity of AEs |  | 12, 18, & 24 months post-implantation | 
| True aneurysm formation (conduit lumen diameter >9mm) | Assessed by ultrasound | 12, 18, 24, & 60 months post-implantation | 
| Pseudoaneurysm formation | Assessed by ultrasound | 12, 18, 24, & 60 months post-implantation | 
| Study conduit rupture | Assessed by ultrasound | 12, 18, 24, & 60 months post-implantation | 
| Anastomotic bleeding or rupture | Assessed by ultrasound | 12, 18, 24, & 60 months post-implantation |