Humacyte's HAV for Femoro-Popliteal Bypass in Patients With PAD

Peripheral Artery Disease Clinical Trial

Official title:

A Phase 2 Study for the Evaluation of Safety and Efficacy of Humacyte's Human Acellular Vessel for Use as a Vascular Prosthesis for Femoro-Popliteal Bypass in Patients With Peripheral Arterial Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02887859
• Other study ID #: CLN-PRO-V004
• Status: Completed
• Phase: Phase 2
• Start date: December 20, 2016
• Est. completion date: December 2023

Study information

• Verified date: February 2024
• Source: Humacyte, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate how well Humacyte's Human Acellular Vessel (HAV) works when surgically implanted into a leg to improve blood flow in patients with peripheral arterial disease (PAD). This study will also evaluate how safe it is to use the HAV in this manner.

Description:

This is a prospective, open label, single treatment arm, multicenter phase 2 study to evaluate the safety and efficacy of the HAV in patients with PAD undergoing femoro-popliteal bypass surgery. The primary objective of this study is to evaluate the safety and tolerability of the HAV in these patients and to determine the patency of the Humacyte HAV at 12 months post-implantation. The secondary objectives of this study are to further assess safety in terms of PRA response, and to determine the rates of HAV interventions required to keep the HAV patent. There is no formal hypothesis testing planned; the study involves only a single, open-label treatment group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2023
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Patients with disabling symptomatic peripheral arterial disease

1. Rutherford stage 4 or 5 who require femoro-popliteal bypass surgery or

2. Rutherford stage 3 with severe claudication (less than 50 yards AND causing severe impairment of ability to work or undertake social activities)

2. Ankle - brachial index = 0.6 in the study leg

3. Patient has failed adequate medical therapy which included

1. Exercise program

2. Smoking cessation therapy

3. Control of diabetes, hypertension and dyslipidemias

4. Antiplatelet therapy

4. Preoperative angiography or CT angiography shows superficial femoral artery occlusion AND required Humacyte Human Acellular Vessel (HAV) length of = 38cm. This imaging may have been conducted up to 6 months prior to study entry provided that the patient's symptoms have remained stable since that time

5. Preoperative imaging shows at least one below knee vessel patent to the ankle with good runoff

6. Proximal HAV anastomosis is expected to be to the common femoral artery below the inguinal ligament or to the superficial femoral artery

7. Distal anastomosis is expected to be to the popliteal artery above the knee

8. Femoral artery occlusion is not considered suitable for endovascular treatment; e.g. long segment chronic total occlusion, previous failed stent or stent graft in the superficial femoral artery, previous failed endovascular treatment where the lesion could not be crossed

9. Autologous vein graft is not feasible in the judgment of the treating surgeon; e.g. because all suitable veins have been used previously for coronary or peripheral bypass, or pre-operative vein mapping shows inadequate length or quality of vein to complete the planned bypass

10. Aged 18 to 85 years old, inclusive

11. Hemoglobin = 10g/dL and platelet count = 100,000/mm3 at screening

12. Other hematological and biochemical parameters within a range considered acceptable for the administration of general anesthesia at screening

13. Adequate liver function, defined as serum bilirubin = 1.5 mg/dL; and INR = 1.5 at screening

14. Able to communicate meaningfully with investigative staff, competent to give written informed consent, and able to comply with entire study procedures

15. Life expectancy of at least 1 year

Exclusion Criteria:

1. Leg at high risk of amputation (SVS WIfI stage 4)

2. Recent clinically significant trauma to the leg receiving the HAV

3. Severe active infection (SVS foot infection grade 3) in the leg receiving the HAV

4. Distal anastomosis planned to a below knee artery

5. 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

6. Stroke within six (6) months prior to study entry (Day 1)

7. Chronic renal disease such that multiple administrations of contrast agents may pose an increased risk of nephrotoxicity (eGFR<45mL/min)

8. Uncontrolled diabetes (HbA1c >10% at screening)

9. Treatment with any investigational drug or device within 60 days prior to study entry (Day 1)

10. Cancer that is being actively treated with a cytotoxic agent

11. AIDS / HIV infection

12. Documented hypercoagulable state or history as defined as either:

1. a biochemical diagnosis (e.g. Factor V Leiden, Protein C deficiency, etc.) - OR -

2. a clinical history of thrombophilia as diagnosed by 2 or more spontaneous intravascular thrombotic events (e.g. DVT, PE, etc.) within the previous 5 years

13. Spontaneous or unexplained bleeding diathesis clinically documented within the last 5 years or a biochemical diagnosis (e.g. von Willebrand disease, etc.).

14. Ongoing treatment with vitamin K antagonists or oral direct thrombin inhibitors or factor Xa inhibitors (e.g. dabigatran, apixaban or rivaroxaban )

15. Previous arterial bypass surgery (autologous vein or synthetic graft) in the operative leg

16. Stenosis of >50% of the inflow aortoiliac system ipsilateral to the index leg. Any such stenosis must be corrected with angioplasty with or without stenting prior to, or at the time of, HAV implantation

17. Active autoimmune disease - symptomatic or requiring ongoing drug therapy

18. Active local or systemic infection (WBC > 15,000/mm3)

19. Known serious allergy to aspirin

20. Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the Humacyte Human Acellular Vessel (HAV)

21. Previous exposure to HAV

22. Employees of the sponsor or patients who are employees or relatives of the investigator

23. Pregnant women or women planning to become pregnant (Women of child bearing potential, WOCBP, must use adequate contraception [hormonal or barrier method of birth control; abstinence] for the duration of study participation; WOCBP defined as not sterile or not > 1 year postmenopausal.)

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Artery Disease

Intervention

Biological:
• Human Acellular Vessel (HAV)
Patients will be implanted with a Human Acellular Vessel (HAV) as a femoro-popliteal bypass conduit using standard vascular surgical techniques

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	Michigan Vascular Center	Flint	Michigan
United States	UCSF	San Francisco	California
United States	Overlook Medical Center	Summit	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Humacyte, Inc.	Atlantic Research Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient Survival		60 months
Other	Frequency of HAV Remaining as a Functional Conduit in Situ (With or Without Interventions)		60 months
Other	Evidence of Aneurysmal Dilatation (Conduit Lumen Diameter >9 mm) or Stenosis of the HAV (>70%) on Routine Clinical US		60 months
Primary	Number of Participants With Aneurysm Formation, Anastomotic Bleeding or Spontaneous Rupture, HAV Infection, HAV Removal, and Significant Inflammation at the HAV Implantation Site		12 months
Primary	Number of Participants With Adverse Events		12 months
Primary	Number of Participants With HAV Patency Rates (Primary, Primary-assisted, Secondary)	Primary patency = patent ("open" to blood flow) without any interventions; Primary-assisted patency = patent without an intervention to clear a thrombus; Secondary patency = patent with or without interventions	12 months
Primary	Number of Participants With Hemodynamically Significant Stenosis (>70% by Duplex Ultrasound Criteria)		12 months
Secondary	Number of Participants With a Change in Panel Reactive Antibodies (PRA) From Baseline		12 months
Secondary	Changes From Baseline in Hematology Parameters - Hemoglobin		12 months
Secondary	Changes From Baseline in Coagulation Parameters - International Normalized Ratio (INR)		12 months
Secondary	Changes From Baseline in Clinical Chemistry Parameters - Sodium, Potassium		12 months
Secondary	Number of Participants With HAV Interventions	e.g., angioplasty, thrombectomy, surgical revision	12 months
Secondary	Mean Vascular Quality of Life Questionnaire (VascuQoL) Score (1-7) for Patients With PAD Symptoms	scoring per Vascular Quality of Life Questionnaire (VascuQoL) Likert scale: 7, there is 1 (the worst) to 7 (the best possible)	12 months
Secondary	Ankle Brachial Index (ABI)	Normal: 1.0 - 1.4 Borderline: 0.9 - 1.0 Mild PAD (peripheral artery disease): 0.8 - 0.9 Moderate PAD: 0.4 - 0.7 Severe PAD: < 0.4	12 months
Secondary	Six Minute Walk Test - Duration		12 months
Secondary	Microscopic Evidence of HAV Remodeling (Host Cells Within HAV)		12 months
Secondary	Changes From Baseline in Hematology Parameters - Hematocrit		12 months
Secondary	Changes From Baseline in Hematology Parameters - Lymphocytes, Monocyte, Eosinophil, Basophil, White Blood Cell, and Neutrophil Counts		12 months
Secondary	Changes From Baseline in Coagulation Parameters - Activated Partial Thromboplastin Time		12 months
Secondary	Changes From Baseline in Clinical Chemistry Parameters - Calcium, BUN, Bilirubin, Creatinine, Glucose		12 months
Secondary	Changes From Baseline in Clinical Chemistry Parameters - Albumin		12 months
Secondary	Six Minute Walk Test - Distance		12 months