Evaluation of the Safety and Efficacy of a Vascular Prosthesis as an Above-Knee Bypass Graft in Patients With PAD

A Pilot Study for Evaluation of the Safety and Efficacy of Humacyte's Human Acellular Vascular Graft as an Above-Knee Femoro-Popliteal Bypass Graft in Patients With Peripheral Arterial Disease

The purpose of this study is to assess the safety and efficacy of a novel, tissue-engineered vascular prosthesis, the Human Acellular Vessel (HAV).

The HAV is intended as an alternative to synthetic materials and to autologous grafts in the creation of an above-knee femoro-popliteal bypass graft in patients with peripheral arterial disease.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Peripheral Vascular Disease
• Intervention / Treatment: Biological: HAV implantation

Detailed Description

The HAV is a sterile, non-pyrogenic, acellular tubular graft composed of human collagens and other natural extra-cellular matrix proteins. Upon implantation, it is anticipated (based on pre-clinical studies) that the collagen-based matrix comprising the graft will be infiltrated with host cells and re-modeled by the host. This will result in a vascular structure more similar to the histological composition of the native vascular tissue that may improve graft longevity and be less likely to become infected.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Lublin, Poland, 20-081
    • Clinic of Vascular Surgery and Angiology; Medical University in Lublin
  • Szczecin, Poland, 70-111
    • Pomeranian University in Szczecin; Clinic of General, Vascular Surgery and Angiology
  • Wrocław, Poland, 51-124
    • Regional Specialist Hospital in Wroclaw; Clinic of Vascular Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with symptomatic peripheral arterial disease who require above knee femoro-popliteal bypass surgery
• Claudication distance of 200 m or less or rest pain or critical limb ischemia
• Preoperative angiography or angio-CT shows superficial femoral artery occlusion of >10 cm AND graft length required ≤ 30 cm. This imaging may have been conducted up to 3 months prior to study entry provided that the patient's symptoms have remained stable since that time
• Preoperative imaging shows at least two below knee vessels patent to the ankle with good runoff
• Femoral artery occlusion is not considered suitable for endovascular treatment
• Autologous vein grafts are not suitable or feasible e.g. because of severe venous disease or prior use of leg veins for other bypass surgery or there is a clinical need to preserve those veins for future bypass surgery in the coronary or peripheral circulation
• Aged 18 to 80 years old, inclusive
• Hemoglobin ≥ 10 g/dL and platelet count ≥ 100,000/mm3 prior to Day 1
• Other hematological and biochemical parameters within a range considered acceptable for the administration of general anesthesia prior to Day 1
• Adequate liver function, defined as serum bilirubin ≤ 1.5 mg/dL; GGT, AST, ALT, and alkaline phosphatase ≤ 2x upper limit of normal or INR ≤ 1.5 prior to Day 1.
• Able to communicate meaningfully with investigative staff, competent to give written informed consent, and able to comply with entire study procedures
• Able and willing to give informed consent
• Life expectancy of at least 2 years

Exclusion Criteria:

• History or evidence of severe cardiac disease (NYHA Functional Class III or IV), myocardial infarction within six months prior to study entry (Day 1), ventricular tachyarrhythmias requiring continuing treatment, or unstable angina
• Acute injury or active infection (including positive cultures of pathogenic bacteria) in the limb receiving the graft
• Stroke within six (6) months prior to study entry (Day 1)
• Treatment with any investigational drug or device within 60 days prior to study entry (Day 1)
• Women of child bearing potential
• Active diagnosis of cancer within the previous year
• Immunodeficiency including AIDS / HIV
• Documented hypercoagulable state or history of 2 or more DVTs or other spontaneous intravascular thrombotic events
• Bleeding diathesis
• Ongoing treatment with vitamin K antagonists or direct thrombin inhibitors or factor Xa inhibitors (e.g. dabigatran, apixaban or rivaroxaban)
• Previous arterial bypass surgery (autologous vein or synthetic graft) in the operative limb
• Previous angioplasty with stenting in the operative limb unless the graft anastomoses can be made at least 1cm distant from the site of the stent
• Stenosis of >50% of the external iliac artery unless it is planned to treat this stenosis with angioplasty with or without stenting prior to, or at the time of, graft implantation
• Distal graft anastomosis likely to be below the knee
• Active autoimmune disease - symptomatic or requiring ongoing drug therapy
• Active local or systemic infection (WBC > 15,000/mm3)
• Known serious allergy to aspirin or penicillin
• Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAVG
• Previous enrollment in this study
• Employees of the sponsor or patients who are employees or relatives of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human Acellular Vessel (HAV); HAV implantation to study participants.	Biological: HAV implantation; Patients will be implanted with a Human Acellular Vessel (HAV) as an above-knee femoro-popliteal bypass graft using standard vascular surgical techniques.; Other Names: Human Acellular Vessel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HAV characteristics	The incidence of aneurysm formation, anastomotic bleeding or rupture, graft infection and irritation/inflammation/infection at the implantation site will be assessed by Doppler ultrasound and tabulated.	From day 5 to month 24 after HAV implantation.
Change in HAV patency rate	Determine the patency (primary, primary assisted and secondary) rate of the Humacyte HAV by Doppler ultrasound.	From day 5 to month 24 after HAV implantation.
Change in frequency and severity of Adverse Events	Frequency and severity of AEs of each patient will be documented.	From day 1 to month 24 after HAV implantation.
Change in hematology, coagulation and clinical chemistry parameters	Change from baseline in hematology, coagulation and clinical chemistry parameters.	From baseline to week 26 after HAV implantation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Panel Reactive Antibody (PRA)	Assess changes in the Panel Reactive Antibody response over 6 months after graft implantation.	From baseline to week 26 after HAV implantation.
Development of IgG antibodies	Determine whether IgG antibodies to the extracellular matrix material are formed in response to implantation of the HAVG over the 6 months after implantation.	From baseline to week 26 after HAV implantation.
HAV patency rates	To determine the patency rates of the graft (primary, primary assisted and secondary).	At months 6, 12, 18 after HAV implantation.
Graft interventions	Determine the rates of interventions needed to maintain / restore patency in the graft.	At days 5, 15, weeks 6, 12, 16, months 12, 18, 24 after HAV implantation.
Effect of graft implantation on PAD symptoms	Assessment of any effect of graft implantation on claudication, rest pain and ischemic ulcers.	From baseline to weeks 6, 12, 26, months 12, 18, 24 after HAV implantation.
Effect of graft on ankle-brachial index (ABI)	Assessment of any effect of the graft on ankle-brachial index (ABI).	From baseline to weeks 6, 12, 26, months 12, 18, 24 after HAV implantation.

Collaborators and Investigators

• Sponsor: Humacyte, Inc.
• Collaborators: FGK Clinical Research GmbH
• Investigators: Study Director: Shamik Parikh, MD, Humacyte, Inc.

Publications and helpful links

General Publications

• Gutowski P, Gage SM, Guziewicz M, Ilzecki M, Kazimierczak A, Kirkton RD, Niklason LE, Pilgrim A, Prichard HL, Przywara S, Samad R, Tente B, Turek J, Witkiewicz W, Zapotoczny N, Zubilewicz T, Lawson JH. Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease. J Vasc Surg. 2020 Oct;72(4):1247-1258. doi: 10.1016/j.jvs.2019.11.056. Epub 2020 Feb 21.

Helpful Links

• Results of the clinical study have been published

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2013
• Primary Completion (Actual): May 30, 2016
• Study Completion (Actual): July 18, 2024

Study Registration Dates

• First Submitted: May 22, 2013
• First Submitted That Met QC Criteria: June 3, 2013
• First Posted (Estimated): June 7, 2013

Study Record Updates

• Last Update Posted (Actual): November 13, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: PAD; Atherosclerosis; Peripheral circulation; Blood Vessel Prosthesis; Tissue-Engineered Vascular Graft; Vascular Prosthesis Implantation; Femoro-Popliteal Bypass
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: CLN-PRO-V002

Plan for Individual participant data (IPD)

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