Humacyte Clinical Trials and Publications

Publications

"Patency of ePTFE Arteriovenous Graft Placements in Hemodialysis Patients: Systematic Literature Review and Meta-analysis"

Kidney 360

2020

"Arterial Reconstruction with Human Bioengineered Acellular Blood Vessels in Patients with Peripheral Arterial Disease"

Journal of Vascular Surgery


2020

"Bioengineered Human Blood Vessels"

American Association for the Advancement of Science

2020

"Challenges and Novel Therapies for Vascular Access in Haemodialysis"

Nature

2020

"Clinical Outcomes of Arteriovenous Access in Incident Hemodialysis Patients with Medicare Coverage 2012-2014"

American Journal of Nephrology

2019

 

"Bioengineered Human Acellular Vessels Recellularize and Evolve into Living Blood Vessels after Human Implantation"

Science Translational Medicine

2019

"Clinical Implementation of the Humacyte Human Acellular Vessel: Implications for Military and Civilian Trauma Care"

The Journal of Trauma and Acute Care Surgery

2019

"Cost Attributable to Arteriovenous Fistulae And Arteriovenous Graft Placements in Hemodialysis Patients with Medicare Coverage"

American Journal of Nephrology


2019

"Susceptibility of EPTFE Vascular Grafts and Bioengineered Human Acellular Vessels to Infection"

Journal Of Surgical Research

2018

"Arteriovenous Fistulae for Hemodialysis: A Systematic Review and Meta-Anaylsis of Efficacy and Safety Outcomes"

European Journal of Vascular and Endovascular Surgery

2017

"Bioengineered Hemodialysis Access Graft"

Journal of Vascular Access


2017

"Bioengineered Human Acellular Vessels for Dialysis Access in Patients with End-Stage Renal Disease: Two Phase 2 Single-Arm Trials"

The Lancet


2016

"An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia"

Journal of Cardiovascular Translational Research

2011

"Readily Available Tissue-Engineered Vascular Grafts"

Science Translational Medicine


2011

"Functional Arteries Grown in Vitro"

Science




1999

VASCULAR ACCESS

Humacyte’s clinical trials are currently evaluating use of the HAV as a hemodialysis vascular access conduit in patients with end-stage renal disease (ESRD). In patients suffering from ESRD hemodialysis is conducted outside of the body- a point of access to the patient’s circulatory system (“vascular access”) must be created so that blood can be transported from the body to the dialyzer, which removes toxins and waste and returns the blood to the patient’s body. Current methods of vascular access are: 1) creation of an arteriovenous fistula (surgically connecting a vein to an artery, typically in the patient’s arm); 2) sewing a synthetic graft such as expanded polytetrafluoroethylene (ePTFE) between an artery and vein in the patient’s arm; and 3) placement of a catheter directly into a large vein in the patient. All three methods are associated with substantial limitations. Some patients are not candidates for a fistula, and in many patients, fistulas fail to ever become usable for dialysis. Synthetic grafts have high rates of bloodstream infections, and the access thickens and narrows over time, eventually making it unusable. Catheters are associated with even higher rates of infection, as well as higher risks for all-cause mortality and cardiovascular events.

The HAV could be an important alternative for hemodialysis as a durable biologic vascular access with lower rates of infection than available methods, improving on current standard of care.

Vascular Access Clinical Program

V001 is an open-label, single treatment pilot study conducted in Poland of the HAV in patients with ESRD receiving hemodialysis who were not candidates for fistula. A total of 40 patients received an HAV and began hemodialysis between 4 to 8 weeks after implantation. The primary safety goal of the study was to evaluate the safety and tolerability of the HAV in ESRD patients undergoing routine dialysis; the primary efficacy goal was to determine the primary, primary assisted and secondary patency rates of the HAV at Month 6. Patients were followed for safety and efficacy for 24 months post-HAV implantation. Patients who had a patent HAV and who were continuing dialysis at Month 24 are continuing to be assessed in long-term follow up for patient and HAV status through 10 years post-implantation.

Results of the clinical study have been published in Lawson et al. Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials. Lancet. 2016 14;387(10032):2026-34.

In addition, results that show remodeling of the HAV to become more similar to the native vasculature are published in Kirkton et al.  Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation. Sci Transl Med. 2019 Mar 27;11(485):eaau6934.

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT01744418.

 

V003 is an open-label, single treatment arm Phase 1 study conducted in the United States of the HAV in patients with ESRD receiving hemodialysis who were not candidates for fistula. Overall, a total of 20 patients were implanted with an HAV as a vascular access for hemodialysis and followed for safety and efficacy for 24 months post-HAV implantation. The primary safety goal was to evaluate the safety and tolerability of the HAV in ESRD patients who were on or were about to start hemodialysis and required an arteriovenous (AV) graft for dialysis access. The primary efficacy goal was to determine the primary, primary assisted, and secondary patency rates of the HAV at 6 months.

Results of the clinical study have been published in Lawson et al. Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials. Lancet. 2016 14;387(10032):2026-34.

In addition, results that show remodeling of the HAV to become more similar to the native vasculature are published in Kirkton et al.  Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation. Sci Transl Med. 2019 Mar 27;11(485):eaau6934.

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT01840956.

V006 is a Phase 3, randomized, two-arm, comparative study conducted in the United States, Germany, Poland, Portugal, United Kingdom (UK) and Israel of the HAV in patients with ESRD who were targeted for implantation of an AV graft for hemodialysis. The study was designed to compare HAV with two common, commercially available ePTFE grafts: Gore® PROPATEN® Vascular Graft or Bard® Impra® Vascular Graft. Eligible patients were randomized to either HAV or ePTFE in a 1:1 manner. Overall, 355 patients were enrolled. All patients are followed through 24 months post-implantation for safety and efficacy. After 24 months, patients with a patent study conduit continue to be followed for up to 5 years post-implantation at routine study visits. The primary goal of the study is to compare the secondary patency of the HAV with that of the ePTFE graft when used as a conduit for hemodialysis. A secondary efficacy objective is to compare the primary patency of the HAV with ePTFE. A secondary safety objective is to compare the rate of access-related infections for the HAV with ePTFE. Other secondary efficacy objectives are to compare rates of interventions, primary assisted patency, and efficiency of dialysis between the HAV and ePTFE and to describe the remodeling of explanted samples from HAV and ePTFE. Other safety objectives were to compare the safety and tolerability of the HAV with ePTFE and to compare relative rates of true aneurysm and pseudoaneurysm formation.     

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT02644941 as well as in the EU Clinical Trials Register using EudraCT Number  .

 

This is a Phase 3, open-label, randomized, two-arm, comparative study conducted in the United States of the HAV in patients with ESRD receiving hemodialysis. Patients are randomized to receive either the HAV for vascular access or an autogenous arteriovenous fistula. Patients are followed for 24 months after creation of the study access (either HAV or fistula) at routine study visits. After 24 months, patients in the fistula group with a fistula that is still patent will be followed (while it remains patent) for up to 5 years. After 24 months, all HAV subjects will be followed, regardless of patency, for 5 years. The primary goals of the study are to compare the ability of the HAV with that of autogenous arteriovenous fistula to support functional hemodialysis.  Key secondary efficacy objectives are to compare time to loss of secondary patency (abandonment) of the HAV with that of autogenous arteriovenous fistula when all subjects have reached 12 months post-study access creation, and to compare the rates of hemodialysis access-related interventions between the HAV and autogenous arteriovenous fistula treatment groups over 12 months post-study access creation. The key secondary safety objective is to compare the rates of hemodialysis access-related infections between the HAV and autogenous arteriovenous fistula treatment groups over 12 months post-study access creation, irrespective of study access abandonment.

This study is currently enrolling as of December 2020. Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT03183245.

This is an open-label, single-arm Phase 2 study conducted in Poland of the HAV in patients with ESRD who are not candidates for autogenous arteriovenous fistula. The purpose of this study is to evaluate HAV that were manufactured on Humacyte’s commercial LUNA platform. Patients will have the HAV implanted in the forearm or upper arm using standard vascular surgical techniques. Subjects will then be followed for safety and efficacy assessments through 12 months, then for up to 36 months (3 years) while the HAV remains patent. The primary goal of the study is to evaluate the safety, efficacy, and immunogenicity of HAVs manufactured using the commercial manufacturing system (LUNA), and the secondary goal is to evaluate the long-term safety and efficacy of the HAV. 

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT04135417 as well as in the EU Clinical Trials Register using EudraCT Number 2018-003570-26.   

VASCULAR TRAUMA

Humacyte’s ongoing clinical trial is evaluating the HAV for use as a replacement vessel in patients who have experienced vascular trauma, that will support the utilization of the product in both military and civilian environments. Arterial injuries resulting from trauma are common in military and civilian populations, frequently resulting in the loss of life or limb. Autologous vein is the preferred conduit for vascular repair due to favorable outcomes when compared to synthetic or other existing biologic alternatives. However, harvesting of autologous vein is not always feasible, due to damage, removal during a prior vein harvest, inadequate size, or venous disease. Even when vein is available, harvesting autologous vein is a serious operation that requires additional time and may have increased risks, including surgical site infections, chronic pain, and limb swelling that severely impact the patient’s quality of life. Despite substantial limitations with autologous vein, synthetic materials remain inferior in resistance to infection and durability and are generally only used when autologous vein is not an option.

The properties of the HAV offer a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma, including rapid off-the-shelf accessibility in time-constrained surgical environments, and reduced risk of infection in “dirty” wounds. The Department of Defense has been working with Humacyte in this indication and has emphasized their urgent need for the availability of the HAV. 

Vascular Trauma Clinical Program

V005 is a non-randomized, open-label Phase 2/3 pivotal study conducted in the United States, Poland, and Israel of the HAV in patients with life- or limb-threatening vascular trauma. In this study, patients with life- or limb-threatening vascular trauma, in either the extremities or the torso, will be implanted with a Humacyte HAV as an interposition replacement or bypass using standard vascular surgical techniques. The primary efficacy goal is to assess the primary patency of the HAV at 30 days in vascular trauma patients undergoing surgery for vascular replacement or reconstruction. The primary safety goal is to evaluate the safety and tolerability of the HAV in vascular trauma patients undergoing surgery for vascular replacement or reconstruction. The secondary efficacy goals are to determine the primary patency of the HAV at 15 days; determine the primary, primary assisted, and secondary patency of the HAV at 6, 12, 24, and 36 months; determine the rates of interventions needed to maintain / restore patency in the HAV; determine the rate of limb salvage in the limb cohort; determine patient survival; determine infection rates of the HAV; evaluate remodeling of the HAV; and assess post-traumatic injury patient lifestyle. The secondary safety goals are to determine mechanical stability of the HAV based on freedom from aneurysmal degeneration, anastomotic bleeding or spontaneous rupture, infection, or significant stenosis; and determine the durability of the HAV repair in terms of freedom from HAV removal or replacement.

V005 is currently enrolling as of December 2020. Details of the study can be found at ClinicalTrials.gov using the Study Identifier .

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT01744418.

Peripheral Arterial Disease (PAD)

The HAV is also being evaluated for use as a bypass conduit for patients with peripheral arterial disease (PAD). PAD involves partial or complete occlusion of blood vessels in the peripheral circulation and is a major cause of morbidity and mortality. Patients with severe PAD undergo peripheral arterial bypass surgery where a conduit is implanted above and below the area of the arterial obstruction, to provide a “bypass” route for blood to flow around the blocked artery, predominately in the lower limb. The various conduits available for peripheral arterial bypass surgery include autologous veins, synthetic grafts, allografts, and xenografts.  Each of these materials has significant limitations, including increased time for vein harvest, increased risk for thrombosis (blood clot) and vessel narrowing (stenosis), and structural degradation that is particularly prevalent for xenogenic materials. 

HAVs may offer an essential alternative to synthetic and autologous materials, including mimicking native vascular tissue and being available off-the-shelf.

Peripheral Arterial Disease Clinical Program

V002 is an open-label, single treatment pilot study conducted in Poland of the HAV in patients with symptomatic PAD and claudication, requiring above-knee peripheral bypass surgery. Patients were implanted with an HAV using standard vascular surgical techniques. Safety and efficacy of the HAV was then followed for 2 years. Efficacy assessments evaluated patency, interventions on the HAV, and disease symptoms. For patients with a patent HAV, safety and efficacy assessments are ongoing through 10 years post-implantation. The primary safety goal was to evaluate the safety and tolerability of the HAV in PAD patients undergoing above-knee femoro-popliteal bypass grafting, and the primary efficacy goal was to determine the primary, primary assisted and secondary patency rates of the HAV over 24 months. Long-term follow up assessments include patency, disease symptoms, ankle-brachial index measuremenets, HAV interventions and complications, and HAV structural integrity.        

Results of the clinical study have been published in: Gutowski et al. Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease. J Vasc Surg. 2020 Oct;72(4):1247-1258.

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT01872208.

 

V004 is a single arm, non-randomized Phase 2 study of the HAV conducted in the United States in patients with symptomatic peripheral vascular disease as evidenced by claudication, rest pain or critical limb ischemia, who are being considered for femoro-popliteal bypass surgery. Patients had the HAV implanted using standard vascular surgical techniques. The primary safety goal is to evaluate the safety and tolerability of the HAV in PAD patients undergoing femoro-popliteal bypass surgery, and the primary efficacy goals are to determine the patency (primary, primary assisted and secondary) rate of the HAV at Month 12 and to determine the incidence of hemodynamically significant stenosis (>70%) defined by duplex ultrasound, and the time to stenosis development. The secondary efficacy objectives are to determine the patency of the HAV (primary, primary assisted and secondary) at Months 3, 6 and 9; determine the rates of interventions needed to maintain / restore patency in the HAV through Month 12; assess effect of HAV implantation on symptoms of peripheral arterial disease using the VascuQol instrument (a questionnaire for assessment of PAD symptoms); assess effect of the HAV on ankle-brachial index; and assess effect of the HAV on 6 minute walk test.

Details of the study can be found at ClinicalTrials.gov using the Study Identifier NCT02887859.

FUTURE APPLICATIONS​

We are currently exploring use of the HAV, including smaller diameter HAVs, for additional vascular applications and as a cell delivery system for treatment of Type 1 diabetes. These indications are in various stages of preclinical development to support planned future IND-filing.

We are developing a smaller diameter HAV product for use in pediatric heart surgery as a BT shunt, a surgical procedure used to increase pulmonary blood flow for the treatment of babies born with Tetralogy of Fallot. Although ePTFE grafts are currently used as the most common BT shunt, they suffer similar limitations described above, such as infection which can be lethal for the child. HAVs are currently being tested as BT shunts in juvenile primates.

CABG is one of the most commonly performed surgical operations in the world. Used to treat atherosclerotic blockage of the arteries supplying the heart, CABG provides a bypass conduit from the aorta to the affected artery supplying the heart muscle. Typically, a CABG operation involves harvesting of both the patient’s own artery and vein to provide suitable vessel conduit to supply blood to the heart. However, many patients do not possess adequate saphenous vein for use in CABG. In patients that do have sufficient vein, comorbidities such as obesity, diabetes, or old age increase risk for vein harvest complications, including failure to heal the vein harvest incision, infection, and prolonged swelling of the operative leg. It is a procedure that would substantially benefit from the HAV.

We have conducted pilot studies for CABG in canines, with promising results. We have initiated a preclinical study to evaluate the use of our small diameter HAV for CABG in adult primates.

Type 1 diabetes, caused by auto-immune destruction of insulin-producing cells in the islets of the pancreas, is a devastating disease, and many patients cannot achieve consistent target blood sugar levels even with the newer insulin delivery technologies. Pancreas transplantation is limited due to the associated morbidity and cost; an alternative “Edmonton Protocol” has been developed whereby insulin producing cells are transplanted into the portal vein in the liver. However, the majority of the injected cells are lost to inflammation and clotting, and only 18% of Type 1 diabetes patients who receive the Protocol are cured long term. The HAV may represent a means to deliver a therapeutic number of pancreatic islets to patients with Type 1 diabetes.  Proof-of-concept studies in rodents and pigs have shown promise that this “Biovascular Pancreas” can reduce glucose levels.  Studies in non-human primates are planned. 

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