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

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

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

Study Overview

• Status: Completed
• Conditions: Renal Failure; Hemodialysis; End Stage Renal Disease; Vascular Access
• Intervention / Treatment: Biological: Human Acellular Vessel (HAV); Device: ePTFE graft

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 355
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitätsklinikmn Erlangen, Gefäßchirurgie - Chirurgisches Zentrum
  • Hessen
    • Frankfurt/Main, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt Klinik für Gefäß- und Endovascular-Chirurgie
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9103102
    • Sharee Zedek Medical Center
  • Tzrifin, Israel, 70300
    • Assaf Harofeh Medical Center
  • Haifa
    • Hadera, Haifa, Israel, 38100
      • Hillel Jaffe Medical Center
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 52621
      • The Chaim Sheba Medical Center
• Poland
  • Poznan, Poland, 61-848
    • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
  • Warszawa, Poland, 02-097
    • Samodzielny Publiczyn Centralny Szpital Klinziczny
  • Wroclaw, Poland, 51-124
    • Oddzial Chirurgii Naczyniowej Wojewódzki Szpital Specjalistyczny we Wrocławiu
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-081
      • Katedra i Klinika Chirurgii Naczyń i Angiologii Uniwersytetu Medycznego w Lublinie
• Portugal
  • Porto, Portugal, 4250-449
    • Hospital da Prelada
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth II Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary
  • London, United Kingdom
    • St. George's Hospital
  • East Midlands/ Leicestershire
    • Leicester, East Midlands/ Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RT
      • Guy´s Hospital, Kings´College London
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • University Hospital Birmingham QE Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Kidney Disease and Hypertension Center (AKDHC)
    • Tucson, Arizona, United States, 85745
      • Carondelet St. Mary's Hospital
  • California
    • Fresno, California, United States, 93710
      • Ladenheim Dialysis Access Center
    • Irvine, California, United States, 92868
      • University of California, Irvine
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Mather, California, United States, 95655
      • Sacramento VA Medical Center
    • San Diego, California, United States, 92123
      • Balboa Nephrology
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Alsip, Illinois, United States, 60803
      • Southwest Vascular Access Center
  • Maryland
    • Easton, Maryland, United States, 21601
      • University of Maryland Shore Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Flint, Michigan, United States, 48507
      • Michigan Vascular Center
  • Mississippi
    • Greenwood, Mississippi, United States, 38930
      • Greenwood Leflore Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers University
    • Summit, New Jersey, United States, 07901
      • Overlook Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97201
      • Kaiser Permanente
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • The Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75226
      • Texas Vascular Associates / Baylor
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Human Acellular Vessel (HAV); Surgical implantation of the HAV and subsequent use of the implanted vascular conduit for hemodialysis vascular access.; Other Names: (regulated as a biological product)
Active Comparator: ePTFE; 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; Surgical implantation of a commercially available ePTFE graft and subsequent use of the implanted vascular conduit for hemodialysis vascular access.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Humacyte, Inc.
• Collaborators: California Institute for Regenerative Medicine (CIRM); CTI Clinical Trial and Consulting Services
• Investigators: Study Director: Shamik Parikh, MD, Humacyte, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2016
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: December 30, 2015
• First Posted (Estimated): January 1, 2016

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: CLN-PRO-V006; 2015-003261-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO