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

Phase 3

Active, not recruiting

Conditions: Hemodialysis
Renal Failure
Vascular Access
End Stage Renal Disease

Interventions: Biological: Human Acellular Vessel (HAV)
Procedure: Arteriovenous fistula (AVF)
Other: Hemodialysis

Registration Number: NCT03183245

Lead Sponsor: Humacyte, Inc.

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

Detailed Description: 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 240

Inclusion Criteria

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.
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.
Subjects aged at least 18 years at Screening.
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.
Hemoglobin ≥8 g/dL and platelet count ≥100,000 /mm3.
International Normalized Ratio (INR) ≤ 1.5.
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.
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 2 years.

Exclusion Criteria

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.
Uncontrolled diabetes;

a. HbA1c >10% (at Screening).
History or evidence of severe peripheral arterial disease in the extremity selected for implant.
Known or suspected central vein stenosis or obstruction on the side of planned SA creation, unless corrected prior to randomization.
Planned AVF creation that requires more than one stage to complete. (e.g. basilic vein transposition AVF performed in 2 stages).
Planned AVF creation by means other than suture or vascular anastomotic clips (e.g. endovascular surgery or other anastomotic creation devices).
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 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)
Anticipated renal transplant within 6 months.
History of heparin-induced thrombocytopenia.
Venous outflow from SA cannot be located more centrally than the venous outflow of any previous failed access in 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 one week post resolution of that infection before SA creation.
Known serious allergy or intolerance to aspirin and alternative antiplatelet therapy.
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 SA.
Previous enrollment in this study or any other study with HAV.
Employees of Humacyte and employees or relatives of an investigator.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Human Acellular Vessel (HAV)	Human Acellular Vessel (HAV)	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.
Human Acellular Vessel (HAV)	Hemodialysis	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.
Arteriovenous fistula (AVF)	Arteriovenous fistula (AVF)	The comparator is an autologous arteriovenous fistula created in the forearm or upper arm on Study Day 0.
Arteriovenous fistula (AVF)	Hemodialysis	The comparator is an autologous arteriovenous fistula created in the forearm or upper arm on Study Day 0.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with functional patency at 6 months post study access (SA) creation	6 months post SA creation	Co-primary endpoint #1: Proportion of subjects with functional patency at 6 months post study access (SA) creation The definition of "functional patency" is: Dialysis with "2 needles for ≥75% of dialysis sessions over a continuous 4-week period and either: (1) 4 consecutive sessions during the 4-week period in which 2 needles are used and the mean dialysis machine blood pump speed is ≥300 mL/min, or (2) a measured spKt/Vurea is ≥ 1.4 or urea reduction ratio \>70% during any session in which 2 needles are used within the 4-week period. SpKt/Vurea is calculated from pre and post-treatment serum urea nitrogen concentrations, body weight, and dialysis session duration." The functional patency ascertainment period will take place between the 1st day of Week 21 (Day 140) and the last day of Week 26 (Day 181) after AVF creation or HAV placement. The endpoint is met when the functional patency criteria are satisfied within any consecutive 4 week period within this ascertainment period.
Proportion of subjects with secondary patency of SA at 12 months post SA creation.	12 months post SA creation	Co-primary endpoint #2: Proportion of subjects with secondary patency of SA at 12 months post SA creation. The SA maintains secondary patency until it is abandoned, irrespective of interventions to maintain or restore patency. Abandonment is defined as AVF or HAV that can no longer be used for 2-needle, prescribed dialysis as it may be unable to provide adequate flows and/or is deemed unsafe for the subject, and the associated problem cannot be corrected by any intervention, including medical, surgical, or radiological interventions or rest.

Secondary Outcome Measures

Name	Time	Method
Frequency and severity of AEs.	12, 24, and 60 months post SA creation
Incidence rate of HD access-related infections over the period from SA creation until SA abandonment.	12, 24, and 60 months post SA creation
Time to loss of primary unassisted patency	12, 24, and 60 months post SA creation
Proportion of HD sessions completed via DC (1 or 2 lines) over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment.	12 months post SA creation
Number of days with DC in situ "catheter contact time" over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment	12 months post SA creation
Time to loss of secondary patency (abandonment).	12, 24, and 60 months post SA creation
Incidence rate of HD access related interventions over the period from SA creation until SA abandonment or 12 months post SA creation	12 months post SA creation
Incidence rate of infections related to any HD access in situ over the period from SA creation until 12 months post SA creation, irrespective of SA abandonment.	12 months post SA creation
Proportion of subjects with unassisted functional patency at 6 months post SA creation.	6 months post SA creation
Incidence rate of HD access-related interventions over the period from SA creation until SA abandonment or the conclusion of the suitability ascertainment period (6 months).	6 months post SA creation
Incidence rate of clinically significant aneurysm or pseudoaneurysm over the period from SA creation until SA abandonment	12, 24, and 60 months post SA creation
Histopathological remodeling of HAV and AVF - based on histological examination of SA samples explanted for clinical reasons	12, 24, and 60 months post SA creation
Incidence rate of SA site infections (CDC definition) over the period from SA creation until SA abandonment.	12, 24, and 60 months post SA creation

Trial Locations

Locations (31): University of California, Irvine
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Irvine, California, United States
Alliance Research
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Laguna Hills, California, United States
University of Southern California
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Los Angeles, California, United States
Balboa Nephrology
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San Diego, California, United States
Grady Memorial Hospital
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Atlanta, Georgia, United States
Brigham and Women's Hospital
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Boston, Massachusetts, United States
VA Pittsburgh
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Pittsburgh, Pennsylvania, United States
Arizona Kidney Disease and Hypertension Center (AKDHC)
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Phoenix, Arizona, United States
Denver Health Medical Center
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Denver, Colorado, United States
Kaiser Permanente Sunnsyide
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Portland, Oregon, United States
UC Davis
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Sacramento, California, United States
University of Arizona
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Tucson, Arizona, United States
University of CA, San Diego - LaJolla VA Hospital
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La Jolla, California, United States
University of California San Diego, Jacobs Medical Center
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La Jolla, California, United States
Huntington Hospital
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Pasadena, California, United States
VA Long Beach Healthcare System
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Long Beach, California, United States
Mills Peninsula Hospital
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San Mateo, California, United States
Olive View- UCLA Medical Center
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Sylmar, California, United States
Memorial Healthcare System
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Pembroke Pines, Florida, United States
The Vascular Experts
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Darien, Connecticut, United States
Coastal Vascular & Interventional, PLLC
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Pensacola, Florida, United States
Tampa General Hospital
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Tampa, Florida, United States
United Surgical Associates
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Lexington, Kentucky, United States
Kidney Care & Transplant Services of New England
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West Springfield, Massachusetts, United States
Rutgers University
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Newark, New Jersey, United States
Overlook Medical Center
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Summit, New Jersey, United States
Surgical Specialists of Charlotte
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Charlotte, North Carolina, United States
The Regional Medical Center
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Orangeburg, South Carolina, United States
University of Tennessee Knoxville
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Knoxville, Tennessee, United States
South Plains Surgery Center
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Lubbock, Texas, United States
Decatur Memorial Hospital
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Decatur, Illinois, United States