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Physicians

HAV-ACCESS
Human Acellular Vessel
– A Controlled Comparison
of Efficacy and Safety Study

ATTENTION CLINICIAN: The purpose of this website is to alert you that this patient is enrolled in the HAV-ACCESS Phase III AV Access Clinical Trial.

PRIOR TO INTERVENTION: We request that you read Intervention Guidelines and refer to the appropriate Medical Monitor phone number listed below if you have questions regarding interventions to this arteriovenous (AV) access.

This patient’s vascular access may be either an autologous arteriovenous fistula (AVF), or the Human Acellular Vessel (HAV).

Be advised, balloon for angioplasty or thrombectomy SHOULD NOT EXCEED 6MM in diameter within the HAV as disruption or tearing of HAV may occur.

Humacyte HAV-ACCESS
Phase III Clinical Trial

STUDY POPULATION:
ESRD patients who are currently receiving hemodialysis with a catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula

STUDY SITES:
Approximately 20 Sites in the United States

ENROLLMENT: 
At least 240 patients

RANDOMIZATION: 
1:1 AVF:HAV

ENROLLMENT PERIOD: 
Approximately 12 months

EXPECTED START DATE: 
August 2017

FOLLOW UP PERIOD: 
Up to 5 years

SPONSOR: 
Humacyte, Inc.

CONTACT:
Medical Monitor by Region
US: 1-800-723-2890

The HAV-ACCESS Phase III clinical trial will compare the HAV with a current standard of care AVF when used for hemodialysis access in the above study population. Below you can review Intervention Guidelines, or below you can review cannulation guidelines or if you would like to learn more about the Humacyte technology, the HAV-ACCESS clinical trial, or Phase II clinical trial results.

Cannulation Guidelines

1. We recommend needle cannulation access of the study implant in accordance with the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines as outlined in CLINICAL PRACTICE GUIDELINES FOR VASCULAR ACCESS, Section I, Guideline 3. http://www2.kidney.org/professionals/kdoqi/guideline_uphd_pd_va/va_guide3.htm

2. For purposes of this clinical trial, the study implant will require 4 weeks of tissue incorporation time prior to cannulation and use for hemodialysis. The surgical clinician must evaluate the patient prior to use to ensure there are no contraindications for cannulation.

3. Great care must be exercised when accessing the study implant so as to not inadvertently puncture through both the anterior and posterior wall of the study implant, which may result in injury or hematoma. This is best accomplished by inserting the needle at a shallow angle (i.e., 25° or less).

4. Techniques and procedures applicable to accessing a native fistula should be practiced. We recommend the use of a 17 gauge needle for access, and a flow rate of 200-250 ml/min during the first week of use. After an initial week of successful use, the dialysis unit may step up to a 16 gauge needle and increase the flow rate to 300-350 ml/min. Assuming no issues with study implant use after the second week, the dialysis unit may increase to use of a 15 gauge needle and, at the nephrologists’ discretion, flow rates above 350 ml/min thereafter.

5. Hemostasis can be achieved with light pressure from a single digit over the puncture site on the access (which may not exactly correspond with the skin puncture site), typically in under 10 minutes.

6. It is essential to properly rotate needle sites in a “rope ladder” technique. Puncture sites must be adequately separated to allow the skin and tissue over the study implant to properly heal between needle punctures. Multiple punctures in the same area may lead to disruption of the study implant material or formation of a perigraft hematoma or pseudoaneurysm.

7. We do not recommend the use of the “button hole” technique for patients in this clinical trial.

Clinical Trial Synopsis - HAV-ACCESS

Official Title of the Clinical Trial:

A Phase 3 Study to Compare the Efficacy and Safety of Humacyte’s Human Acellular Vessel with that of an Autologous Arteriovenous Fistula in Subjects with End‑Stage Renal Disease

Subjects with end-stage renal disease (ESRD) who are currently receiving hemodialysis with a catheter (e.g. Permcath™) and who are suitable candidates for placement of a dialysis graft or creation of a dialysis fistula will be considered for participation in this prospective, multicenter, randomized, comparative study. Subjects will be implanted with either a HAV or will have an AVF created in the forearm or upper arm using standard vascular surgical techniques. The 1:1 randomization will occur in the operating room, but prior to skin incision, and will be stratified by upper arm or forearm placement based on the Investigator’s determination of where the Study Access (SA) should be located. All subjects will be required to take daily aspirin (81-325 mg) unless they are already taking another antiplatelet agent. Subjects who are known to be aspirin-sensitive should take another antiplatelet agent at the discretion of the Investigator.

Each subject will be followed by study specific visits until the patient completes 2 years (24 months) of follow-up after implantation (irrespective of patency status). After 2 years, subjects with a HAV (irrespective of patency) and subjects with a patent AVF will be followed (while the study access remains patent) for up to 5 years (60 months) post-implantation at routine study visits. The expected duration of the clinical investigation is about 75 months (initiation of enrollment through completion of data collection).

Primary Endpoints:

Co-primary Endpoint #1:
Proportion of subjects with functional patency at 6 months post SA creation.
  • The definition of “functional patency” is that which Dember, et al, of the Hemodialysis Fistula Maturation Study Group described as “clinical maturation.” (Dember 2014)
    • 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/V urea is ≥ 1.4 or urea reduction ratio >70% during any session in which 2 needles are used within the 4-week period. SpKt/V urea 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 180) after SA creation. The endpoint is met when the functional patency criteria are satisfied within any consecutive 4 week period within this 6-week ascertainment period. Regular use of the SA for functional hemodialysis (HD) prior to the ascertainment period does not count towards achievement of this endpoint. If a subject has not begun dialysis with 2 needles by Week 23, he or she will not achieve functional patency as defined for this co-primary endpoint.
Co-primary Endpoint #2:
Proportion of subjects with secondary patency 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. (Lee 2011)

SECONDARY ENDPOINTS

Efficacy
  • Time to loss of secondary patency (abandonment).
    • Defined as the time from SA creation until SA abandonment.
  • Incidence rate of HD access related interventions over the period from SA creation until SA abandonment or 12 months post SA creation.
    • For purposes of this study, HD access refers to any surgically created permanent access or device to provide a route for HD (e.g. SA, previous AVF or AVG, dialysis catheter [DC]).
Safety
  • 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.
Study Product: The Investigational Medicinal Product is Humacyte’s HAV, a human tissue-engineered vascular conduit for hemodialysis access.

The comparator will be creation of autologous AVF

Humacyte Vessel

The HUMACYTE HAV is a tissue-engineered blood vessel that is being investigated as a surgical option for vascular access. The HAV is a sterile, vascular tube, composed of human connective tissue and proteins. This complex connective tissue has similarities to human vascular tissue but HAV is non-living. To date, the HAV has been implanted in over 250 patients worldwide in various clinical trials.

To read more about the Humacyte HAV, click here.

Phase II Clinical Trial Results

The following clinical data were adapted from the Humacyte Phase II AV access clinical trial results as reported by Lawson, et al. The Lancet, May 2016.

Two, single arm Phase II clinical trials were conducted in adults in the US and Poland to evaluate the safety and efficacy of the novel bioengineered HAV when implanted into the arms of patients with ESRD who were deemed not suitable for fistula creation to create a vascular access for dialysis.

Primary endpoints were safety (freedom from immune response/infection, aneurysm, or mechanical failure, incidence of adverse events). Efficacy was assessed by primary, primary assisted and secondary patencies at 6 months. Secondary endpoints included patency and intervention rates at 12, 18 and 24 months, and changes in panel reactive antibodies (PRA) following HAV implantation. During the course of the trial, 60 HAVs were implanted into the arms of 60 patients at 6 centers across the US and Poland with planned 24 months of follow up. All patients in this report were followed for at least 1 year, or had a censoring event.

Conclusion: The results of the Phase II clinical trials provide evidence of the potential safety and effectiveness of the bioengineered HAV when used for hemodialysis access as well as evidence of HAV repopulation with host vascular cells, but warrant further study in randomized controlled clinical trials.

US / POLAND
COMBINED

NUMBER OF PATIENTS IMPLANTED

60

PATENCY - NUMBER (%)

PRIMARY PATENCY

6 MONTHS36 (63%)

12 MONTHS15 (28%)

PRIMARY ASSISTED PATENCY

6 MONTHS41 (73%)

12 MONTHS20 (38%)

SECONDARY PATENCY

6 MONTHS54 (97%)

12 MONTHS 46 (89%)

INTERVENTIONS (PER PATIENT YEAR)

1.89

HAV INFECTION, NUMBER (%PPY)

1(1.3%)