Humacyte Human Acellular Vessel (HAV) in Patients With Vascular Trauma

Study Overview
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Brief Summary
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This study evaluates the use of the Human Acellular Vessel (HAV) in adults with vascular trauma below the neck who are undergoing vascular reconstructive surgery. There will be a torso cohort and a limb cohort. All subjects will be implanted with a HAV as an interposition vessel or bypass using standard vascular surgical techniques. There is no control arm.

Detailed Description
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This is a prospective, multicenter, multi cohort, non-randomized phase 2 study in up to 40 adult patients with life or limb threatening vascular trauma which requires surgical repair. There will be a limb cohort and a torso cohort. The limb cohort will include patients who require repair of a vessel contained to the upper or lower extremity. The torso cohort includes patients who require repair of vessels within the thorax (excluding the heart), abdomen, and retroperitoneum. Subjects will be implanted with a Humacyte Human Acellular Vessel (HAV) as an interposition vessel or bypass using standard vascular surgical techniques. There is no control arm. The active study duration for each study participant will be 36 months from HAV implantation or until HAV failure/ removal/ death if earlier. Follow up after month 12 will involve the capture of information on assessments performed at standard of care routine clinic visits or by telephone follow up with the patient or his/her physician with physical exam and ultrasound at month 24 and month 36 The total expected duration of the clinical study is 61 months (24 months of enrollment and 36 months of follow up).

Official Title
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A Phase 2/3 Study for the Evaluation of Safety and Efficacy of Humacyte's Human Acellular Vessel for Vascular Replacement or Reconstruction in Patients With Life or Limb-threatening Vascular Trauma

Conditions
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Trauma, Vascular System Injury

Intervention / Treatment
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* Biological: Human Acellular Vessel (HAV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, which requires replacement or reconstruction Preoperative imaging or clinical examination indicates the damaged vessel has a defect length of ≤ 38cm and is appropriately size matched to the 6mm Human Acellular Vessel (HAV) per the judgment of the treating surgeon taking into account vasoconstriction and situational inflow and outflow considerations. Autologous vein graft is either not feasible in the judgment of the treating surgeon (e.g. because of lack of availability of suitable conduit, presence of severe venous insufficiency) or is not desirable because of the urgency of revascularization Aged 18 to 85 years old, inclusive Able to communicate meaningfully with investigative staff, and able to comply with entire study procedures. If the patient is unconscious, then information from a reliable witness indicates that the patient would normally be able to comply with study procedures Patient or relative is able, willing and competent to give informed consent Life expectancy of at least 1 year Exclusion Criteria: Mangled Extremity Severity Score (MESS) of ≥ 7 Limb at high risk of amputation despite vascular reconstruction (e.g., because of crush injury) Catastrophic injuries that make survival unlikely (e.g. Abbreviated Injury Scale (AIS) > 5 or Injury Severity Score (ISS) >60) HAV may not be used for coronary artery repair Known pregnant women Known medical condition which would preclude long term antiplatelet therapy after resolution of acute injuries Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV Previous exposure to HAV Known participation in any investigational study within the last 30 days Employees of the sponsor or patients who are employees or relatives of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Acellular Vessel (HAV)<br>Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, will be implanted with the Humacyte Human Acellular Vessel (HAV) as an interposition vessel or bypass using standard vascular surgical techniques. | Biological: Human Acellular Vessel (HAV)<br>* The investigational medicinal product (IMP) - the Human Acellular Vessel (HAV) is a sterile acellular tubular graft composed of human collagen types I and III and other extracellular matrix proteins, including fibronectin and vitronectin which can be used for arterial bypass or reconstruction in patients with life or limb threatening vascular trauma. The vessel is 6 mm in diameter and approximately 42 cm in length. The product is supplied on a silicone mandrel immersed in sterile phosphate buffered saline in a sealed and labeled plastic container. The Humacyte HAV is implanted using standard vascular surgical techniques similar to placement of predicate peripheral vascular prostheses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAV primary patency | Primary patency is defined as 'the interval from the time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis or the measurement of patency', i.e., patent without interventions | 30 days | 
| Frequency and Severity of Adverse Events |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Limb viability (avoidance of amputation; limb cohort only) |  | 36 months | 
| HAV primary patency | Primary patency is defined as 'the interval from the time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis or the measurement of patency', i.e., patent without interventions | 36 months | 
| HAV primary assisted patency | Primary assisted patency is defined as 'the interval from the time of access placement until access thrombosis or the time of measurement of patency, including intervening manipulations (surgical or endovascular interventions) designed to maintain the functionality of patent access' i.e., patent without an intervention to clear a thrombus | 36 months | 
| HAV secondary patency | Secondary patency is defined as 'the interval from the time of access placement until access abandonment', i.e., patent with or without interventions | 36 months | 
| Rate of HAV interventions |  | 36 months | 
| Patient survival |  | 36 months | 
| HAV remodeling as shown by histopathology of any clinical explants |  | 36 months | 
| Frequency of anastomotic bleeding or spontaneous rupture |  | 36 months | 
| Frequency of HAV infection |  | 36 months | 
| Frequency of HAV thrombosis |  | 36 months | 
| Frequency of HAV pseudoaneursym formation |  | 36 months | 
| Frequency of HAV aneursym formation |  | 36 months | 
| Frequency of HAV of hemodynamically significant stenosis (>70% by duplex ultrasound criteria) |  | 36 months | 
| Frequency of HAV removal |  | 36 months |