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
Phase: PHASE2
Conditions: Peripheral Artery Disease
Sponsor: Humacyte, Inc.

Humacyte, Inc. 
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Study No. CLN-PRO-V004 
 
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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  
 
Medicinal Product: 
Humacyte Human Acellular Vessel (Humacyte HAV) 
Study No.: 
CLN-PRO-V004 
IND No: 
16,746 
Sponsor: 
Humacyte, Inc.  
Address: 
2525 East NC Highway 54 
Durham, NC 27713 
Phone: 
919-313-9633 
 
CRO: 
Atlantic Research Group, Inc. 
 
2421 Ivy Road, Suite 200 
 
Charlottesville, VA 22903 
 
 
Version:  
4.0 (Amendment to version 3.0 dated 16 July 2018) 
1 Oct 2020 
 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, applicable independent ethics committees or institutional 
review boards, and competent authorities. The contents of this document shall not be disclosed 
to others without written authorization from Humacyte, Inc. (or others, as applicable), unless it is 
necessary to obtain informed consent from potential study participants. 
 

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STATEMENT OF COMPLIANCE 
This trial will be conducted in compliance with the protocol and the following regulatory 
requirements:  
● Declaration of Helsinki adopted by the 18th World Medical Assembly in Helsinki, Finland, 
in 1964, as last amended by the World Medical Assembly in 2013 
● International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH), E6 Good Clinical Practice: Consolidated Guidance 
(ICH E6) 
● ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting 
● ICH E8 Guidance on General Considerations for Clinical Trials 
● Applicable sections of United States Food and Drug Administration (FDA) Code of Federal 
Regulations (CFR), including: 
o 21 CFR Part 11, Electronic Records; Electronic Signatures 
o 21 CFR Part 50, Protection of Human Subjects 
o 21 CFR Part 54, Financial Disclosure by Clinical Investigators 
o 21 CFR Part 56, Institutional Review Boards 
o 21 CFR Part 312, Investigational New Drug Application 

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PRINCIPAL INVESTIGATOR AGREEMENT PAGE FOR THE 
PROTOCOL 
I agree: 
● To assume responsibility for the proper conduct of the study at this site, and to conduct 
the study in compliance with this protocol, any future amendments, and with any other 
study conduct procedures provided by the sponsor, Humacyte, Incorporated (Humacyte), 
or their authorized representatives. 
● Not to implement any deviations from or changes to the protocol (including protocol 
amendments) without agreement from the sponsor and prior review and written approval 
from the Institutional Review Board (and FDA, if applicable) except where necessary to 
eliminate an immediate hazard to the patient(s), or for administrative aspects of the study 
(where permitted by all applicable regulatory requirements). 
● That I am familiar with the appropriate use of the investigational medicinal product, as 
described in this protocol and any other information provided by the sponsor including, but 
not limited to the current Investigator Brochure or equivalent document provided by 
Humacyte. 
● To ensure that all persons assisting me with the study are adequately informed about the 
investigational medicinal product and of their study-related duties and functions. 
● That I have been informed that certain regulatory authorities require the sponsor to obtain 
and supply details about the investigator’s ownership interest in the sponsor or the 
Investigational Medicinal Product, and more generally about his/her financial ties with the 
sponsor. Humacyte will use and disclose the information solely for the purpose of 
complying with regulatory requirements. 
 
 
Principal Investigator:  _______________________________________________ 
Name and Title 
 
Signed: 
 
Date: 
 
 

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PROTOCOL APPROVAL 
 
 
 
 
Sponsor Medical Approval:  Kiernan DeAngelis, MD, VP Clinical, Humacyte Inc 
Name and Title 
 
Signed: 
 
Date: 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
STATEMENT OF COMPLIANCE .................................................................................... 2 
PRINCIPAL INVESTIGATOR AGREEMENT PAGE FOR THE PROTOCOL ................. 3 
PROTOCOL APPROVAL ................................................................................................ 4 
LIST OF ABBREVIATIONS ........................................................................................... 10 
PROTOCOL SUMMARY ............................................................................................... 12 
1. STUDY PERSONNEL............................................................................................. 19 
2. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ......................... 21 
2.1. 
Background Information ................................................................................. 21 
2.2. 
Scientific Rationale ......................................................................................... 21 
2.3. 
Summary of Nonclinical Information ............................................................... 22 
2.4. 
Summary of Clinical Studies .......................................................................... 24 
2.4.1. Overview ................................................................................................ 24 
2.4.2. Experience in Peripheral Arterial Bypass Patients ................................. 24 
2.4.3. CLN-PRO-V002 Study Results (24 M) ................................................... 25 
2.4.4. Experience in Hemodialysis Patients ..................................................... 26 
2.4.5. CLN-PRO-V001 and CLN-PRO-V003 Study Results (24 M) ................. 27 
2.4.6. CLN-PRO-V006 Preliminary Study Results (18 M) ................................ 28 
2.4.7. Human Acellular Vessel Host Response and Remodeling Data ............ 30 
2.4.8. Conclusions ........................................................................................... 32 
2.5. 
Potential Risks and Benefits ........................................................................... 32 
2.5.1. Potential Risks ....................................................................................... 32 
2.5.2. Potential Benefits ................................................................................... 33 
2.5.3. Risk-Benefit Rationale ........................................................................... 33 
3. STUDY OBJECTIVES ............................................................................................ 34 
3.1. 
Primary Objectives ......................................................................................... 34 
3.2. 
Secondary Objectives .................................................................................... 34 
4. STUDY DESIGN ..................................................................................................... 35 
4.1. 
Description of the Study Design ..................................................................... 35 
4.2. 
Study Endpoints ............................................................................................. 35 

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4.2.1. Primary Endpoints ................................................................................. 35 
4.2.2. Secondary Endpoints ............................................................................. 35 
4.2.3. Long Term Endpoints (post Month 12 through Month 60) ..................... 36 
4.3. 
Duration of Study Participation ....................................................................... 36 
5. STUDY POPULATION ............................................................................................ 37 
5.1. 
Description of the Study Population ............................................................... 37 
5.1.1. Patient Inclusion Criteria ........................................................................ 37 
5.1.2. Patient Exclusion Criteria ....................................................................... 38 
6. INVESTIGATIONAL MEDICINAL PRODUCT ......................................................... 40 
6.1. 
Product Description ........................................................................................ 40 
6.2. 
Manufacturer of the IMP ................................................................................. 40 
6.3. 
Packaging, Storage, and Labeling ................................................................. 40 
6.4. 
Implantation of the Humacyte human acellular vessel (HAV) ......................... 41 
6.5. 
IMP Accountability Procedures ...................................................................... 41 
6.6. 
Assessment of Patient Compliance with IMP ................................................. 41 
6.7. 
Prior and Concomitant Medications ............................................................... 41 
6.8. 
Essential, Precautionary and Prohibited Medications .................................... 42 
6.8.1. Essential Medications ............................................................................ 42 
6.8.2. Restricted Medications .......................................................................... 43 
7. STUDY PROCEDURES / EVALUATIONS ............................................................. 44 
7.1. 
Clinical Evaluations Through Month 12 .......................................................... 44 
7.2. 
Clinical Evaluations in Long Term Follow Up (Post Month 12 to Month 
60) ........................................................................................................... 45 
7.3. 
Laboratory Evaluations ................................................................................... 45 
7.3.1. Clinical and Research Laboratory Evaluations and Specimen 
Collection ........................................................................................ 45 
7.4. 
Imaging Evaluations ....................................................................................... 46 
7.4.1. CT angiography ..................................................................................... 46 
7.4.2. Duplex ultrasound .................................................................................. 46 
7.5. 
Study Schedule .............................................................................................. 47 
7.5.1. Screening (Day -35 to Day -1) ............................................................... 47 
7.5.2. Enrollment – Day 1 (HAV Implantation) ................................................. 48 

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7.5.3. Follow-up Visits Day 5 through Month 12 .............................................. 48 
7.5.4. Long Term Follow Up Post Month 12 through Month 60 (± 30 
days) ............................................................................................... 50 
7.5.5. Early Termination Visit ........................................................................... 50 
7.5.6. Unscheduled Visits ................................................................................ 51 
7.6. 
Medical Care during the Study and upon Study Termination ......................... 51 
7.7. 
Histological Examination of Resected HAV Material ...................................... 51 
8. SAFETY ASSESSMENTS AND ADVERSE EVENTS ............................................ 52 
8.1. 
Adverse Event Definition ................................................................................ 52 
8.2. 
Serious Adverse Event Definition ................................................................... 52 
8.3. 
Suspected Unexpected Serious Adverse Reaction ........................................ 53 
8.4. 
Events of Special Interest ............................................................................... 53 
8.5. 
Reporting of Adverse Events .......................................................................... 54 
8.5.1. Criteria for Determining Causal Relationship to the HAV and 
Criteria for Determining Causal Relationship to the Index 
Surgical Procedure .......................................................................... 54 
8.5.2. Criteria for Defining the Severity of an Adverse Event ........................... 56 
8.5.3. Reporting of Action Taken to Resolve AE .............................................. 56 
8.5.4. Reporting the Outcome of the AE .......................................................... 56 
8.5.5. Reporting Serious Adverse Events ........................................................ 57 
8.5.6. Reporting of Events of Special Interest .................................................. 58 
8.5.7. Follow-Up of Adverse Events ................................................................ 58 
8.6. 
Reporting of Pregnancy .................................................................................. 58 
8.7. 
Data Monitoring Committee ............................................................................ 59 
8.8. 
Interim Analysis and Stopping Criteria ........................................................... 59 
9. STATISTICAL CONSIDERATIONS ........................................................................ 60 
9.1. 
Analysis Population ........................................................................................ 60 
9.2. 
Safety Analyses ............................................................................................. 60 
9.3. 
Efficacy Analyses ........................................................................................... 60 
9.4. 
Other Analyses ............................................................................................... 61 
9.5. 
Sample Size Rationale ................................................................................... 61 
9.6. 
Interim analyses ............................................................................................. 61 

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10. STUDY MANAGEMENT AND DATA COLLECTION .............................................. 62 
10.1. Ethical Conduct of the Trial ............................................................................ 62 
10.2. Institutional Review Board .............................................................................. 62 
10.3. Subject Informed Consent .............................................................................. 62 
10.4. Amendments to the Protocol .......................................................................... 63 
10.5. Study Initiation ................................................................................................ 63 
10.6. Study Monitoring ............................................................................................ 63 
10.7. Case Report Form .......................................................................................... 64 
10.8. Verification Procedures .................................................................................. 64 
10.9. Retention of Records ...................................................................................... 64 
10.10. Protocol Deviations ........................................................................................ 65 
10.11. Insurance and Indemnity ................................................................................ 65 
10.12. Audit ............................................................................................................... 65 
11. REPORTING .......................................................................................................... 66 
12. QUALITY CONTROL AND QUALITY ASSURANCE .............................................. 67 
13. RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR ................................. 68 
13.1. Informed Consent ........................................................................................... 68 
13.2. Compliance with the Protocol ......................................................................... 68 
13.3. Medical Care of Patients ................................................................................ 69 
13.4. Safety Reporting ............................................................................................ 70 
14. SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL 
INVESTIGATION ......................................................................................... 71 
15. PUBLICATION POLICY .......................................................................................... 72 
16. REFERENCES ....................................................................................................... 73 
APPENDIX 1. 
HAV CLINICAL VISIT SCHEDULE ................................................. 75 
 
 
 

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LIST OF TABLES 
Table 1: 
Summary of Mechanical Properties of Explanted Acellular Vessels .........................22 
Table 2 
Summary of Secondary Patency Losses - ITT Set .....................................................28 
Table 3 
Summary of Access-Related Infections in V006 ........................................................30 
 
LIST OF FIGURES 
Figure 1: 
Images of Mid-Vessel Segment Explanted at 11-Months Post-Implant ....................31 
 
 

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LIST OF ABBREVIATIONS  
ABI 
Ankle brachial index 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
aPTT 
Activated partial thromboplastin time 
AV 
Arteriovenous 
AVF 
Autologous arteriovenous fistula 
BUN  
Blood urea nitrogen 
CAVG 
Canine acellular vascular graft 
CT 
Computed tomography 
CM 
Concomitant medication 
eCRF 
Electronic case report form 
CRO 
Contract research organization 
DMC 
Data Monitoring Committee 
DTH 
Delayed-type hypersensitivity 
ECG 
Electrocardiogram 
ECM 
Extracellular matrix 
EDFMV 
Endothelium-dependent flow-mediated vasodilation 
ePTFE 
Expanded polytetrafluoroethylene 
ESRD 
End-stage renal disease 
ET 
Early termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HAV 
Human Acellular Vessel 
HCG 
Human chorionic gonadotropin 
HIV 
Human immunodeficiency virus 
IB 
Investigator Brochure 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IgG 
Immunoglobulin G 
IHC 
Immunohistochemistry 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 

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IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
IU 
International unit 
IV 
Intravenous 
LMWH 
Low molecular weight heparin 
MedDRA 
Medical Dictionary for Regulatory Activities 
M 
Month 
N 
Number (typically refers to participants) 
NYHA 
New York Heart Association 
OTC 
Over-the-counter 
PAD 
Peripheral arterial disease 
PE 
Physical examination 
PI 
Principal Investigator 
PORF 
Pregnancy & Outcome Report Form 
PRA 
Panel reactive antibodies 
PTFE 
Polytetrafluoroethylene 
RBC 
Red blood cells 
RMST 
Restricted mean survival time 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
SVS WIfI 
Society for Vascular Surgery: Wound, Ischemia, and foot Infection 
US 
Ultrasound 
USA 
United States of America 
WBC 
White blood cell(s) 
WOCBP 
Women of child bearing potential 
 
 

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PROTOCOL SUMMARY 
Full 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 Phase 
Phase 2 
Sponsor  
Humacyte, Inc. 
Planned Study Sites 
Up to 8 sites in the United States  
Sample Size 
Up to 25 patients  
Study Population 
Patients with peripheral arterial disease (PAD) 
Inclusion Criteria 
1. Patients with disabling symptomatic peripheral arterial 
disease  
a. Rutherford stage 4 or 5 who require femoro-
popliteal bypass surgery or 
b. 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 (ABI) ≤ 0.6 in the study leg 
3. Patient has failed adequate medical therapy which 
included 
a. Exercise program 
b. Smoking cessation therapy 
c. Control 
of 
diabetes, 
hypertension 
and 
dyslipidemias 
d. Antiplatelet therapy 
4. Preoperative angiography or computed tomography (CT) 
angiography shows superficial femoral artery occlusion 
AND required Humacyte Human Acellular Vessel (HAV) 
length of ≤ 38 cm. This imaging may have been conducted 
up to 6 months prior to study entry (Day 1) 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 

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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 ≥ 10 g/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 international normalized ratio (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 (New York 
Heart Association [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) 

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7. Chronic renal disease such that multiple administrations of 
contrast agents may pose an increased risk of 
nephrotoxicity (eGFR < 45 mL/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. Acquired immunodeficiency syndrome (AIDS) / human 
immunodeficiency virus (HIV) infection 
12. Documented hypercoagulable state as defined as either: 
a) a biochemical diagnosis (e.g. Factor V Leiden, Protein 
C deficiency, etc.)   - OR - 
b) 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 (white blood cells 
[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 

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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.) 
Expected Enrollment 
Start 
4 Q 2016 
Accrual Period 
36 months 
Study Duration 
The active study duration for each study participant will be 
60 months from HAV implantation.  The total expected duration of 
the clinical investigation is 97 months. 
Study Design 
Prospective, multicenter, single arm, non-randomized study 
Investigational 
Product/Intervention 
Description 
Patients will be implanted with a HAV as a femoro-popliteal 
bypass conduit using standard vascular surgical techniques.  
Primary Objectives 
 
Safety 
● To evaluate the safety and tolerability of the Humacyte 
HAV in PAD patients undergoing femoro-popliteal bypass 
surgery 
Efficacy 
● To determine the patency (primary, primary assisted and 
secondary) rate of the Humacyte HAV at Month 12 
● To 
determine 
the 
incidence 
of 
hemodynamically 
significant stenosis (> 70%) defined by duplex ultrasound, 
and the time to stenosis development 
Secondary Objectives 
Safety  
● To assess changes in the panel reactive antibodies (PRA) 
response after HAV implantation 
● To determine mechanical stability of the HAV based on 
freedom from aneurysmal degeneration on duplex 
ultrasound and CT imaging 

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● To determine HAV durability in terms of freedom from 
need for HAV explantation or replacement due to infection, 
bleeding, or conduit degeneration 
Efficacy 
● 
To determine the patency of the HAV (primary, primary 
assisted and secondary) at Months 3, 6 and 9 
● 
To determine the rates of interventions needed to maintain 
/ restore patency in the HAV through Month 12 
● 
To assess effect of HAV implantation on symptoms of PAD 
using the VascuQol instrument 
● 
To assess effect of the HAV on ABI 
● 
To assess effect of the HAV on 6 minute walk test 
Endpoints 
Endpoints will be assessed over a period of up to 60 months after 
HAV implantation. The primary analysis of the study will be 
conducted on the earlier of a) when the final subject enrolled 
reaches 12 months post-implant or b) all subjects enrolled in the 
initial 36 month accrual period have reached 12 months 
post-implant. 
 
Primary Endpoints: 
● 
Incidence of HAV aneurysm formation (true or pseudo) 
● 
Anastomotic bleeding or spontaneous rupture 
● 
HAV infection 
● 
HAV removal 
● 
Significant local inflammation at the HAV implantation site 
● 
Frequency and severity of adverse events 
● 
HAV patency rates (i.e., primary, primary assisted, and 
secondary) 
● 
Hemodynamically significant stenosis (> 70% using 
duplex ultrasound criteria) 
 
Secondary Endpoints: 
● 
Change from baseline in PRA 
● 
Change from baseline in hematology, coagulation, and 
clinical chemistry parameters 

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● 
HAV interventions  
● 
Patient reported PAD symptoms (VascuQol) 
● 
ABI 
● 
6 minute walk test 
● 
HAV remodeling at Months 1 (Day 29), 6 and 12 by CT 
angiography and US 
 
Long Term Endpoints (post Month 12 through 60): (to be 
evaluated at specified study visits): 
● 
HAV interventions 
● 
Evidence of aneurysmal dilatation or stenosis of the HAV 
on routine clinical duplex US 
● 
Primary, primary assisted, and secondary patency at 18, 
24, 30, 36, 42, 48, 54 and 60 months 
● 
Limb salvage/amputation at 18, 24, 36, 48, and 60 months, 
for all subjects who have not died, withdrawn, or been lost 
to follow-up. 
● 
Incidence of surgical revascularization of the implanted 
limb, at the level of the HAV or distal to HAV, for all patients 
who have not died, withdrawn, or been lost to follow-up. 
● 
VascuQol PAD symptom assessment consists of 25 
questions.  The total score and the 5 domain scores 
(Activity, Symptom, Pain, Emotional, and Social) will be 
recorded in the clinical database, at 18, 24, 36, 48 and 60 
months, for all patients who have not died, withdrawn, or 
been lost to follow-up.   
Protocol Approval 
(Version and Date) 
 
Version 4.0 (1 Oct 2020) 
 
 
 

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Schematic of Study Design: (obtain informed consent prior to any study-specific activities) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-enrollment activities: Standard pre-op assessments. 
Angiography or CT angiography within the previous 6 months. 
Vein mapping within the previous 6 months to exclude the availability of a suitable 
autologous conduit  
Day – 35 to Day – 1 (Screening): Document medical history including PAD history 
(claudication distance, rest pain, ischemic ulcers), PAD symptoms (VascuQol), co-
morbidities, medications and prior vascular interventions. Review pre-op angiography 
or CT angiography & vein mapping for vascular anatomy. Hematology, clinical 
chemistry, coagulation and PRA. Physical examination (PE); ABI; ECG; vital signs;  
6 minute walk test. Confirm eligibility. 
Day 1: Changes to medical history since screening and confirm eligibility.  Surgical 
placement of HAV (incl. documentation of surgical procedure and any complications); 
Confirmation of patency (HAV assessment) by intraoperative angiography and PE of 
HAV site; baseline intraoperative HAV assessment by US; AEs; HAV interventions; 
vital signs, concomitant medications (CMs). 
Day 5 (or prior to discharge if earlier): PE of HAV site, lymphadenopathy, size and 
number of ischemic lesions and to assess AEs; vital signs; AEs; HAV interventions; 
CMs. 
Day 29 (± 4 days): PAD symptoms (VascuQol); ABI; PE of HAV site, 
lymphadenopathy, size and number of ischemic lesions and to assess AEs; vital 
signs; HAV assessment by duplex US; CT angiography of HAV; AEs; HAV 
interventions; CMs; endothelium-dependent, flow-mediated vasodilatation (EDFMV, 
subset of patients). 
Months 3, 6, 9, 12 (± 14 days): PAD symptoms (VascuQol); ABI; PE of HAV site, size 
& # of ischemic lesions, and to assess AEs; 6 minute walk test (Months 3 and 12 
only), vital signs; HAV assessment by clinical duplex US (& high resolution duplex US 
@ Months 3, 6, 12); AEs; HAV interventions; CMs; hematology, clinical chemistry, 
coagulation, PRA (all lab tests at Month 6 only); CT angiography of HAV (Months 6 
&12 only); EDFMV (subset of patients; Month 12 only) 
Every 6 months through Month 60 (± 30 days): PAD symptoms (VascuQol), ABI, 
PE of HAV site, HAV assessment by clinical duplex US (months 18-54) and CT 
angiography (M60 only); SAEs and Events of Special Interest; HAV Interventions 

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1. 
STUDY PERSONNEL 
An updated list of all study personnel will be maintained by the CRO. Protocol amendments will 
not be required for staff changes at Humacyte, the CRO or the sites (except change of Principal 
Investigator at a site). 
CRO Project Manager: 
 
Brad Whitlow 
Project Manager 
Atlantic Research Group 
2421 Ivy Road, Suite 200 
Charlottesville, VA 22903, USA 
 
Email: 
bwhitlow@atlanticresearchgroup.com 
Mobile: 828-442-0526 
Office: 434-202-4537 
Fax: 
434-202-4537 
 
 
Sponsor Medical Representative: 
 
Kiernan DeAngelis, MD 
VP Clinical 
Humacyte, Inc. 
2525 East NC Highway 54 
Durham, NC 27713, USA 
 
Email: 
kdeangelis@humacyte.com  
Mobile: 443-386-3759 
Office: 919-313-9633 
 
 
 
 
Sponsor Regulatory Representative: 
 
William Tente  
Chief Regulatory Officer 
Humacyte, Inc.  
2525 East NC Highway 54 
Durham, NC 27713, USA 
 
Email: 
tente@humacyte.com  
Mobile: 401-714-4151 
Office: 919-313-9633     
 
Sponsor Clinical Operations 
Representative: 
 
Angela Rose 
Sr. Director, Clinical Development 
Humacyte, Inc. 
2525 East NC Highway 54 
Durham, NC 27713, USA 
 
Email: 
 rose@humacyte.com 
Mobile: 
919-667-3507 
Office: 
919-313-9633    
 
 

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CRO Safety Representative: 
 
Todd Fisher 
Sr. Drug Safety Specialist 
Atlantic Research Group 
2421 Ivy Road, Suite 200 
Charlottesville, VA 22903 USA 
 
Email: 
safety@atlanticresearchgroup.com  
Phone: 
888-619-3216 
Fax: 
866-851-9318 
 
 
CRO Medical Monitor: 
 
Jennifer Prichard, MD 
Medical Monitor 
Atlantic Research Group 
2421 Ivy Road, Suite 200 
Charlottesville, VA 22903 USA 
 
Email: jprichard@atlanticresearchgroup.com 
Mobile: 434-249-5530 
Phone: 888-619-3216 
Fax: 
866-851-9318 
 
 

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2. 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1. 
Background Information 
Peripheral arterial disease (PAD), involving atherosclerosis with complete or partial occlusion of 
blood vessels in the peripheral circulation, is a major cause of morbidity and mortality in the 
developed world. It is estimated to affect between 8 and 12 million people in the United States of 
America (USA) (Criqui, 1997). In many patients, peripheral arterial disease is asymptomatic and 
its importance lies mainly as a marker of generalized atherosclerosis and the associated high risk 
of myocardial infarction and stroke (Hirsch, 2001). Peripheral arterial disease may however cause 
disabling symptoms, progressing from intermittent claudication which limits mobility, to rest pain 
and ultimately to critical ischemia of the limb necessitating amputation.  
In many patients, the disease can be managed effectively with medical therapy including 
antiplatelet agents and statins, and an exercise program to increase exercise tolerance. However, 
in more severe disease a range of techniques have been developed to improve or restore blood 
flow to the affected limb. Depending on the anatomical location and extent of the atherosclerotic 
lesions, percutaneous procedures such as angioplasty and stenting may be effective to reopen 
blocked vessels. However, for long segment stenosis and occlusions, bypass grafting with 
autologous vein or synthetic grafts such as polytetrafluoroethylene (PTFE) or DacronTM may be 
required (Norgren, 2007; Conte, 2015). The long-term success of these procedures, particularly 
those using synthetic grafts, is limited by early thrombotic occlusion and by later neo-intimal 
hyperplasia leading to stenosis at the anastomoses. In addition, infection is a common occurrence 
associated with synthetic grafts. This additional hazard is compounded by the difficulties 
frequently encountered with antibiotic treatment of these infections. 
There is thus a need for alternative conduits which more closely mimic human vascular tissue, 
that may avoid or reduce the complications associated with PTFE and Dacron. 
2.2. 
Scientific Rationale 
Humacyte, Inc. (Humacyte) has developed an acellular, human collagen-based vessel (Human 
Acellular Vessel – HAV) to provide an alternative to synthetic materials and to autologous grafts 
for the creation of vascular access for dialysis and for use in peripheral vascular bypass surgery. 
Because this product mimics native vascular tissue, it may possess the advantages of an 
autologous graft as well as the off-the-shelf availability benefit of synthetic grafts. Use of an 
off-the-shelf product avoids the surgical morbidity associated with vein graft harvest and, most 

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importantly, allows vessel bypass surgery in patients who have no suitable veins available. 
Because the product mimics native vessel, it may not have the compliance mismatch associated 
with synthetic alternatives. In addition, pre-clinical studies in pigs, canines and primates have 
shown that the HAVs resist intimal hyperplasia at the anastomoses (Quint, 2011, Prichard, 2011, 
Dahl, 2011). Upon implantation, it is anticipated (based on pre-clinical studies) that the collagen 
matrix comprising the HAV will be infiltrated with host cells and remodeled by the host. This could 
result in a vascular structure that is more similar to the histological composition of the native 
vascular tissue that may improve HAV longevity and be less likely to become infected. 
2.3. 
Summary of Nonclinical Information 
The nonclinical testing program was designed to comprehensively address: 
● local and systemic effects of the product in multiple in vivo animal models acutely and 
chronically, 
● functional aspects of product implanted into animal models as an arteriovenous conduit, 
● biocompatibility of the HAV material in standardized in vitro and in vivo test protocols. 
● Overall, the results of these studies indicated that the HAV extracellular matrix (ECM) 
material was non-toxic, well tolerated, and met standards for biocompatibility. Generally, 
the HAVs functioned as intended and maintained patency during the implantation period. 
(See the Investigator Brochure [IB] for a detailed summary of nonclinical data.) 
● Pre-implantation, the HAV has mechanical properties (burst pressure and suture retention 
strength) comparable with native human artery and vein (Table 1). There was no evidence 
that HAV strength deteriorated after long-term implantation into baboons. 
Table 1: 
Summary of Mechanical Properties of Explanted Acellular Vessels 
a From L’Heureux et al, Nature Medicine, 2006. (L’Heureux, 2006) 
In the chronic animal testing, Humacyte grafts produced using canine cells were implanted into 
12 canines (canine acellular vascular graft, CAVG) and 14 baboons (HAV) in a variety of 
anatomical locations. In general, the Humacyte vessels were safe and well tolerated and 
functioned as intended.  
Test Material 
Burst Pressure (mm Hg) 
Suture Strength (g) 
Pre-Implant Humacyte HAVs 
3415 ± 1011 (n=4) 
180 ± 44 (n=12) 
Post-Explant Humacyte HAVs 
3669 ± 1305 (n=5) 
276 ± 84 (n=11) 
Human Saphenous Vein 
1,680 – 2,273a 
196 ± 2 (n=7)a 
Human Artery 
2,031 – 4,225a 
200 ± 119 (n=9)a 

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Mechanical failure was not observed in any HAV. Calcification was not observed in any CAVG or 
HAV. No graft exhibited hemodynamically significant intimal hyperplasia. Unlike with PTFE graft 
implantation, no evidence of systemic infection attributable to implantation of HAV was observed 
in any of the animals. One HAV developed an aneurysm that was resected and did not harm the 
animal. The HAV material showed no evidence of toxicity in hematology, clinical chemistry, and 
necropsy data. The HAVs could be accessed by venipuncture, and hemostasis was achieved 
following needle puncture.  
On microscopic analysis, the HAVs were found to be well integrated into the host tissue. Overall, 
the cellular host response to the HAVs demonstrated smooth muscle actin-positive cells within 
the vessel wall, endothelial cells lining the lumen, and an adventitial-like outer layer adjacent to 
the vessel. These findings indicate that implanted HAVs were populated with cell types that are 
characteristic of healthy native vasculature. Examination of the anastomotic sections showed that 
the HAVs were well integrated with adjoining vasculature with minimal intimal hyperplasia 
observed. Furthermore, immunohistochemistry (IHC) was employed to identify CD-68 positive 
macrophages in the venous intimal tissue. Studies have shown a substantial macrophage 
population has been observed within venous intimal tissue adjacent to inflammatory PTFE 
arteriovenous grafts (Kelly, 2002, Roy-Chaudhury, 2001). Only sparse CD-68 positive 
macrophages were observed, indicating that the degree and the aggressiveness of the intimal 
hyperplasia associated with the HAV were less than that typically associated with PTFE grafts 
(Prichard, 2011). 
Over time, the organization and composition of ECM components indicated that, aided by 
infiltration of host vascular cells, HAVs were remodeled in vivo in a manner that mimicked the 
dynamic remodeling process of native blood vessels. Given the difficulties associated with the 
baboon animal model, where mismatches in vein versus graft diameter were encountered and 
animals perturbed their wounds postoperatively, an overall assisted patency rate of approximately 
80% (11/14) was achieved. In a xenogeneic transplant model that did not employ 
immunosuppression, the HAV material did not elicit biologically significant cellular or delayed-type 
hypersensitivity (DTH) immune responses. All animals developed immunoglobulin G (IgG) titers 
to the HAV material that did not appear to detrimentally impact vessel function. 
In internationally recognized in vitro and in vivo International Organization for Standardization 
(ISO) test protocols, the HAV material met criteria for biocompatibility required of medical devices.  
These data collectively support the safety of the HAV for the proposed clinical investigation. 
 

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2.4. 
Summary of Clinical Studies 
2.4.1. 
Overview 
The HAV clinical development program currently includes 8 clinical studies: 5 in patients with 
end-stage renal disease (ESRD) receiving hemodialysis (CLN-PRO-V001, CLN-PRO-V003, 
CLN-PRO-V006, CLN-PRO-V007, and CLN-PRO-V011), 2 in patients with PAD (CLN-PRO-V002 
and CLN-PRO-V004) and 1 in patients with vascular trauma (CLN-PRO-V005). Three Phase 1/2 
studies have completed primary analysis with long-term follow-up ongoing (CLN-PRO-V001, 
CLN-PRO-V002 and CLN PRO V003), 1 Phase 3 study completed enrollment and follow up is 
ongoing (CLN-PRO-V006), 2 Phase 2 studies (CLN-PRO-V004 and CLN-PRO-V005) and one 
Phase 3 study (CLN-PRO-V007) are open for enrollment. One Phase 2 study has completed 
enrollment and primary analysis is ongoing (CLN-PRO-V011).   
As of 20 February 2020, 392 patients (330 ESRD patients, 35 PAD patients, and 27 vascular 
trauma patients) have received a HAV. The first implant for hemodialysis was performed in 
December 2012, and the first peripheral arterial bypass in October 2013. Overall, the total 
treatment exposure is approximately 523 patient-years in the hemodialysis access population and 
81 patient-years in the PAD population. More information on the clinical profile of the HAV in these 
ongoing studies is provided in the Investigator Brochure. 
2.4.2. 
Experience in Peripheral Arterial Bypass Patients 
Humacyte has two Phase 2 studies to assess the safety and efficacy of the HAV when used as 
an above-knee arterial bypass graft. The first study, CLN-PRO-V002, is a single group 
uncontrolled study conducted at 3 sites in Poland that is fully enrolled and in long-term follow up. 
Eligible patients required a femoro-popliteal bypass graft for the management of symptomatic 
PAD. Pre-operative imaging (angiography or computed tomography [CT] angiography) must have 
demonstrated at least two below knee vessels patent to the ankle with good runoff. The proximal 
anastomosis was expected to be below the inguinal ligament and the distal anastomosis above 
the knee. Autologous vein grafts must not have been 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).  
The HAV was implanted using standard vascular surgical techniques and the patency of the 
bypass confirmed by intraoperative angiography or ultrasound. The patient was then followed up 

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at study visits at 15 days, 6 weeks and 3, 6, 12, 18 and 24 months. At each visit, safety was 
assessed by clinical examination and adverse events (AEs), and the HAV was examined using 
duplex ultrasound (US) to visualize the entire length to confirm patency, flow and to detect 
stenosis, aneurysm development or dilatation.  
The primary objectives of the study are to evaluate the safety and tolerability of the Humacyte 
HAV in PAD patients undergoing above-knee femoro-popliteal bypass surgery and to determine 
the patency (primary, primary assisted and secondary) rate of the Humacyte HAV at 24 months. 
Secondary objectives include assessment of the panel reactive antibodies (PRA) and IgG 
response to the HAV and to assess patency (primary, primary assisted and secondary) at 6, 12 
and 18 months, to determine the rates of interventions needed to maintain / restore patency in 
the HAV, to assess any effect of implantation on claudication, rest pain and ischemic ulcers and 
to assess any effect on ankle-brachial index (ABI). 
The second PAD study of similar design, CLN-PRO-V004, is being conducted in the US. 
2.4.3. 
CLN-PRO-V002 Study Results (24 M) 
Recruitment began in October 2013 and was completed in June 2014 with 20 patients implanted. 
Thirteen patients completed the 2 year follow up visit. Of the seven patients terminating the study 
early, three died and four were withdrawn after occlusion of the HAV.  None of the deaths were 
considered related to the investigational device or procedure. 
Kaplan-Meier analyses in which deaths were censored revealed primary, primary assisted, and 
secondary patency probability rates of 79.2%, 79.0%, and 89.5% at Week 26, 63.3%, 63.2%, and 
84.2% at Month 12, 63.3%, 63.2%, and 79.0% at Month 18, and 58.1%, 57.9%, and 73.7% at 
Month 24. 
Six patients (30%) required at least 1 graft intervention to maintain or restore HAV patency during 
the study. Four patients required 1 intervention and 1 patient each required 3 and 4 interventions. 
Most interventions successfully restored patency. However, in 1 patient the graft patency could 
not be restored and the HAV was replaced with an alternative bypass graft. Two patients, who 
had previously undergone successful interventions, developed a recurrent thrombosis which was 
not treated and the HAV was left occluded. Two patients experienced HAV thrombosis with no or 
minimal symptoms and refused interventions on the HAV.  

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All 20 patients experienced AEs (a total of 92 events). Thirty-one of these events in 13 patients 
were considered serious. The most frequent AEs reported included graft thrombosis (35% of 
patients), anastomotic stenosis (20% of patients), lymphocele (20% of patients), and local 
swelling (15% of patient). Those serious adverse events (SAEs) reported by at least 2 patients 
were graft thrombosis (6 patients, 30%) and anastomotic stenosis (2 patients, 10%). 
No patient showed an increase in PRA levels. Two patients had a significant (>2-fold) increase 
from baseline in IgG levels. One of these patients experienced a thrombosis of the HAV between 
3 and 6 months after implantation, while the other patient has had no HAV-related AEs and 
continues to have primary patency. Neither patient has had any evidence of dilatation or structural 
degeneration of the HAV. 
CLN-PRO-V002 Conclusions:  
● 
Humacyte HAV was safe and well tolerated in PAD patients.  
● 
The HAV is able to withstand long term use in a high pressure, high outflow resistance 
arterial circuit.  
● 
Patency rates for the HAV are within the ranges of patency rates of synthetic and 
autologous grafts presented in the literature.  
● 
Humacyte HAV was not immunogenic.  
2.4.4. 
Experience in Hemodialysis Patients 
Two Phase 2 trials, one in Poland (CLN-PRO-V001) and one in the US (CLN-PRO-V003) have 
completed enrollment. Both recruited subjects requiring hemodialysis access for ESRD whom 
were not suitable for creation of an autologous arteriovenous fistula (AVF). Most subjects had 
undergone previous vascular access procedures, in many cases multiple attempts including both 
AVFs and synthetic grafts. Initial results from these Phase 2 studies are discussed below.   
The primary objectives of these two studies are to evaluate both the safety of HAV and its efficacy 
in terms of primary and secondary patency at 6 months. Secondary objectives include 
measurement of a PRA response, development of IgG antibodies to the ECM material in the HAV 
and a 2-year evaluation of patency and an assessment of the need for interventions to 
maintain/restore patency. Follow up has now been extended up to 120 months. 
A Phase 3 randomized study comparing HAV with expanded PTFE (ePTFE) grafts (CLN-PRO-
V006) has completed enrollment in the US, Europe, and Israel. Preliminary Month 18 results are 
presented below. A second Phase 3 randomized study (CLN-PRO-V007) comparing HAV with 

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AVF is currently enrolling in the US. As the sponsor is blinded, no efficacy information currently 
available for CLN-PRO-V007; however, blinded safety data is presented in the IB. A Phase 2 
study of ESRD patients in Poland (CLN-PRO-V011) has primary assessments ongoing, and no 
safety or efficacy information is currently available.  
2.4.5. 
CLN-PRO-V001 and CLN-PRO-V003 Study Results (24 M) 
All subjects (n=60) have now completed at least 24 months since implantation (or had a censoring 
event). The first subjects recruited are now beyond 60 months after HAV implantation, some with 
functioning HAV for hemodialysis access. Together these two trials provide more than 150 years 
of follow up during which the HAV has been used for more than 15,000 hemodialysis sessions.  
When HAV thrombosis has occurred, it has almost always been managed successfully, often 
allowing immediate resumption of dialysis without the need for the placement of a dialysis 
catheter. One non-serious arteriovenous (AV) graft aneurysm was reported in Study 
CLN-PRO-V001 (moderate in intensity, considered possibly related to the investigational 
medicinal product [IMP] and considered not related to procedure – this patient died before the 
Sponsor could complete the follow up of this event). An expected number of small 
pseudoaneurysms have been observed, which is consistent with all surgically-created 
hemodialysis access. Most have resolved spontaneously with only 2 cases requiring surgical 
intervention. Flow rates through the HAV were more than sufficient to allow for effective dialysis.  
In both studies, the product has generally been well tolerated and blood chemistry, hematology 
and coagulation data are not indicative of any HAV-associated toxicity.  Immunogenic response 
to the HAV material has not been observed as demonstrated by a general lack of HAV-related 
change in PRA levels (Class I or II). Three subjects had elevations in their PRA levels: all 
3 subjects had experienced one or more renal transplant failures; one subject recently; one 
subject developed septic shock about a month before the elevated value; and the third subject, 
who was severely debilitated with a decubitus ulcer, died approximately a month after HAV 
abandonment.   
IgG titers increased in 5 subjects; in 4 cases, the IgG titer increased and then decreased while 
the HAV remained functional with no clinical evidence of an inflammatory response; in one case 
the IgG titer increase occurred in a subject who maintained primary patency.  

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AEs related to the HAV / access site (excluding thrombotic events) were few; there have been 
only three access-site infections, of which only one required removal of part of the HAV. There 
have been:  
● 
1 transplant (known to be functioning well at 12 months post-transplant) 
● 
15 deaths, all after abandonment or during follow-up; none of the deaths were 
considered related to the presence of the HAV 
Patency data for the two studies in dialysis access has been pooled for a combined Kaplan Meier 
analysis (Lawson, 2016). Based on these Kaplan-Meier plots, the patency at 6, 12 and 24 months 
is estimated to be 60%, 26% and 15% (primary patency) and 97%, 89% and 77% (secondary 
patency). 
2.4.6. 
CLN-PRO-V006 Preliminary Study Results (18 M) 
Details of Study CLN-PRO-V006 can be found in the IB. The CLN-PRO-V006 study was designed 
to enroll a broad range of ESRD patients in whom a clinical decision has been made to implant a 
‘graft’ to provide vascular access for hemodialysis. The trial was limited to adults (≥18 years old), 
and subjects were either on hemodialysis or expected to start dialysis within 12 weeks of conduit 
implantation. The standard synthetic graft implanted in this clinical setting is an ePTFE graft 
(6 mm by 40 mm, straight, standard wall, non-stretch, and non-tapered).  
The primary objective 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. Key secondary objectives of the study 
are to compare the primary patency of the HAV with that of the ePTFE graft (efficacy) and to 
compare the rate of access-related infections for the HAV with that of the ePTFE graft (safety). 
A summary of losses of secondary patency (events) for ePTFE and HAV are shown in Table 2. 
At 6 and 12 months post-implantation, the HAV arm had 9 and 6 fewer losses, respectively, of 
secondary patency than the ePTFE arm. At 18 months, the ePTFE arm had 4 fewer losses of 
secondary patency than the HAV arm.   
Table 2 
Summary of Secondary Patency Losses - ITT Set 
Time Point 
Number of 
ePTFE Patency 
Losses 
ePTFE Kaplan-Meier 
Probability of 
Patency 
Number of HAV 
Patency 
Losses 
HAV Kaplan-Meier 
Probability of 
Patency 
6 Months 
21 
88.0% 
13 
92.3% 
12 Months 
33 
80.7% 
29 
81.8% 
18 Months 
37 
77.6% 
41 
73.0% 
ePTFE=expanded polytetrafluoroethylene; HAV=Human Acellular Vessel; ITT=Intent to Treat 

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The CLN-PRO-V006 Statistical Analysis Plan pre-specified the use of the Cox Proportional 
Hazards model to compare the secondary patency rates of HAV and ePTFE. The observed 
hazard ratio for loss of secondary patency at 18 months is 1.19, with lower and upper 95% 
confidence interval (CI) of 0.78 and 1.81, respectively. Since the observed upper 95% CI is greater 
than the non-inferiority margin, we failed to reject the null hypothesis, and therefore, could not 
establish non-inferiority of HAV relative to ePTFE.   
However, given that the hazards for loss of secondary patency between HAV and ePTFE were 
not proportional (i.e., the curves for secondary patency cross near 400 days, making the relative 
risks of loss of patency non-proportional over time), the pre-specified Cox Proportional Hazards 
model is not ideally suited to analysis of the CLN-PRO-V006 secondary patency data. Therefore, 
a sensitivity analysis was performed using the non-parametric restricted mean survival time 
(RMST) method, which does not make assumptions regarding proportionality of hazards between 
the two arms of the trial. RMST estimates a gain or loss in the event-free survival time due to 
treatment versus control in a specified time period. The results from the RMST analysis indicated 
that the time to failure of secondary patency was delayed, on average, by 11 days in the HAV 
arm compared to the ePTFE arm at the 18 month time point, and non-inferiority of the HAV in 
comparison to ePTFE was demonstrated with this alternative RMST analysis.  
The time to loss of primary patency was significantly shorter for the HAV than for ePTFE, with a 
hazard ratio of 1.89. Since losses of primary patency for the HAV seemed to briefly accelerate 
around 60 to 90 days, it is unclear the extent to which study-mandated ultrasounds at 60 and 
90 days, combined with the lack of experience in managing the HAV at most study sites, may 
have triggered interventions on the HAV study conduit that would have led to a loss of primary 
patency at those times. 
Information on access-related infections was collected for all study subjects. Table 3 provides the 
rates of access-related infections involving the study conduit (not local site infections, and not 
infections of tunneled dialysis catheters or other accesses). The HAV had significantly fewer study 
access-related infections than ePTFE (p= 0.041), with the absolute rate of infections for ePTFE 
roughly five times higher than HAV (4.76 vs. 0.97 infections per 100 subject years of dialysis use 
for ePTFE and HAV, respectively). Fewer HAV subjects required intravenous antibiotics for 
treating their access related infections.  Markedly fewer HAV subjects required hospitalization for 
infection (13 vs. 3 instances of hospitalization for infection with ePTFE and HAV, respectively). 
Lastly, conduit removals were more frequent for ePTFE than for HAV.   

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Table 3 
Summary of Access-Related Infections in V006 
Clinical Event 
ePTFE 
(N = 178) 
HAV 
(N = 177) 
Total 
(N = 355) 
Conduit Infections per 100 subject-years of dialysis 
4.76 
0.97 
(p=0.041) 
Subjects Needing IV Antibiotics 
15 
9 
24 
Subjects Needing Hospitalization 
13 
3 
18 
Conduit Removals (partial and complete) 
8 
13 
21 
ePTFE = expanded polytetrafluoroethylene, HAV = Human Acellular Vessel, IV = intravenous 
2.4.7. 
Human Acellular Vessel Host Response and Remodeling Data 
Humacyte has been able to assess the general host response to the HAV in a number of human 
participants; this was accomplished through the microscopic examination of explanted HAV and 
adjoining tissue samples obtained during surgical revision procedures (Kirkton, 2019). The 
analysis (mostly of a section close to the venous anastomosis) included assessments of:  
● 
Cellular infiltration of histotypic, inflammatory and immunological populations. 
● 
Extracellular remodeling processes, including neo-synthesis and reorganization of 
ECM components that typically occur in native blood vessels. 
In 16 cases, small segments of the HAV and adjacent vascular tissue were explanted, fixed in 
formalin solution and shipped to Humacyte for analysis. Implant duration ranged from 16 to 
200 weeks.  
In man, the HAV remodeled in a manner consistent with that observed in primate studies. There 
was infiltration of cell populations that are normally associated with angiogenesis and vascular 
organization and structure; namely, those with endothelial, smooth muscle and fibroblastic 
phenotypic characteristics were observed. Endothelial cells formed a monolayer on the luminal 
surface of the HAV. Migration of actin-positive smooth muscle cells into the wall of the HAV was 
consistently observed. A well-vascularized adventitial layer of non-constrictive fibrous tissue 
formed around HAV. Infiltration of the graft material by inflammatory and immunoreactive cell 
populations was either not evident or was mild and generally unremarkable. Degradation or 
breakdown of the implant was not observed.  
Histotypic neo-synthesis and reorganization of the ECM was observed in patterns indicative of 
integration of the HAV into the host. An increase in the density of collagen type I, the main type 
of collagen found in the wall of native blood vessels, was apparent in the majority of HAV explant 
specimens. The structure of collagen type I in these specimens exhibited a more mature, 

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organized pattern, with distinct fibers and a prominent circumferential alignment evident in 
explanted samples in comparison with pre-implant specimens. In some specimens, the fibrillar 
staining pattern of collagen III became more prominent and more organized, with a circumferential 
orientation. Fibronectin levels and staining patterns remained unchanged.  
Cannulation sites within the HAV appeared to be repaired by the host in a fashion similar to wound 
repair in the body (Figure 1). In one case, an explanted specimen was tested for suture retention 
strength at the time of explant and exhibited a substantial increase over the pre-implant level. 
Figure 1: 
Images of Mid-Vessel Segment Explanted at 11-Months Post-Implant 
 
 
A: Low magnification showing 3 cannulation sites (in dashed boxes),  
B: Fresh cannulation track,  
C: Cannulation track during remodeling 
D: Older cannulation track that has been repaired.  
The image above shows a mid-vessel segment explanted at 11 months post-implant and shows 
several prior cannulation tracts from dialysis access. Figure 1B shows a very recent cannulation 
site with fresh clot extending into the tract from the lumen.  Figure 1C and D show partially healed 

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cannulation tracts, with evidence of cellular repopulation extending in from the lumen. Remodeled 
cannulation tracks contain new collagen and a few micro-conduits. 
In conclusion, the HAVs were remodeled by the host to form a vascular-like structure more similar 
to the histological appearance of native vasculature. The HAVs were repopulated by cell types 
that are characteristic of healthy native vasculature. Evidence of ECM remodeling processes, 
including neo-synthesis and reorganization of ECM components that typically occur in native 
blood vessels, were observed. The cellular infiltration and ECM remodeling patterns were 
indicative of the integration of the HAV into the host. 
2.4.8. 
Conclusions 
Clinical experience indicates that the HAV remains mechanically strong over implantation periods 
of more than 60 months with no evidence of dilatation. The HAV profile includes use as a 
hemodialysis access in ESRD subjects, an arterial bypass conduit in PAD and vascular trauma 
subjects, and an interposition vessel in vascular trauma subjects. The benefit-risk for the HAV 
remains favorable in these subject groups and continued clinical development for these target 
indications is warranted. The SAE profile has been typical of that expected in the dialysis and 
PAD populations. In hemodialysis populations, secondary patency of the HAVs is substantially 
higher than the historical data for both ePTFE and AVF (accounting for non-maturation). In PAD, 
patency is in line with historical ePTFE and autologous conduit for above-knee bypass.  No 
evidence of immunogenicity of the HAV has been found, and the HAV remains mechanically 
robust even after repeated puncture for hemodialysis and under high pressure, high outflow 
resistance in arterial reconstruction.  
These data support the use of HAV in future Phase 2 and Phase 3 studies for vascular 
replacement and reconstruction in diseased or damaged (trauma) vessels.  
2.5. 
Potential Risks and Benefits 
2.5.1. 
Potential Risks 
It is anticipated that subjects participating in the study will be exposed to similar risks to those 
associated with other arterial conduits. Risks associated with the study investigational product 
may include but are not limited to: 
● 
Thrombosis/occlusion of the conduit or host vessels, with consequent limb ischemia 
● 
Embolism from a thrombosed conduit 

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● 
Bleeding and hematoma formation at the surgical site  
● 
Infection – at the surgical site or systemic 
 
● 
Stenosis of the conduit or its anastomoses 
● 
Aneurysm or pseudoaneurysm formation  
● 
Swelling of the limb 
Regular clinical examination of the HAV implantation site and assessment of the patency, blood 
flow and diameter using ultrasound during the study should allow early detection of complications 
and permit appropriate intervention including HAV explantation. CT angiography at Months 1, 6, 
12 and 60 will allow the detection of anatomical abnormalities of the HAV such as localized dilation 
and intimal hyperplasia. 
The HAV is grown using donor human aortic smooth muscle cells. The HAV is decellularized 
during manufacturing and thus consists of human ECM proteins. It is possible that the HAV may 
provoke an immune response which may lead to damage to the HAV and possible cross reactivity 
against host proteins. Possible antibody formation will be assessed by analyzing PRA. 
2.5.2. 
Potential Benefits 
Patients who undergo implantation of the Humacyte HAV may benefit from a reduced number of 
infections and infection-related complications versus a conventional ePTFE or a Dacron graft. In 
addition, the risks listed in Section 2.5.1 typically encountered with conventional synthetic grafts 
may be decreased with the Humacyte HAV. Finally, the longevity (secondary patency) of the 
Humacyte HAV may be greater than that of conventional synthetic grafts.  
2.5.3. 
Risk-Benefit Rationale 
The risks anticipated in this study are similar to those associated with currently marketed 
prosthetic grafts used for peripheral bypass surgery. The potential advantages of the HAV 
compared to currently marketed grafts may lead to a lower infection rate and reduced need for 
HAV replacement.  
Recruitment will be restricted to a maximum of 25 subjects who receive implants to provide safety 
and efficacy data in the PAD population. 
There is no formal hypothesis testing in this study, but data from the study will be compared with 
historical data on synthetic peripheral bypass grafts to assess the safety and efficacy of the HAV. 

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3. 
STUDY OBJECTIVES 
3.1. 
Primary Objectives 
This is an open label Phase 2 study. There is no formal hypothesis testing. 
Safety: 
● 
To evaluate the safety and tolerability of the Humacyte HAV in PAD patients 
undergoing femoro-popliteal bypass surgery 
Efficacy: 
● 
To determine the patency (primary, primary assisted and secondary) rate of the 
Humacyte HAV at Month 12  
● 
To determine the incidence of hemodynamically significant stenosis (>70%) defined 
by duplex ultrasound, and the time to stenosis development 
3.2. 
Secondary Objectives 
Safety: 
● 
To assess changes in the PRA response after HAV implantation 
● 
To determine mechanical stability of the HAV based on freedom from aneurysmal 
degeneration on duplex ultrasound and CT imaging 
● 
To determine HAV durability in terms of freedom from need for HAV explantation or 
replacement due to infection, bleeding or conduit degeneration 
Efficacy: 
● 
To determine the patency of the HAV (primary, primary assisted and secondary) at 
Months 3, 6 and 9 
● 
To determine the rates of interventions needed to maintain / restore patency in the 
HAV through Month 12 
● 
To assess effect of HAV implantation on symptoms of PAD using the VascuQol 
instrument 
● 
To assess effect of the HAV on ABI 
● 
To assess effect of the HAV on 6 minute walk test 

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4. 
STUDY DESIGN 
4.1. 
Description of the Study Design 
Prospective, multicenter, single arm, non-randomized Phase 2 study  
4.2. 
Study Endpoints 
Endpoints will be evaluated at multiple time points up to 60 months after HAV implantation. The 
primary analysis of the study will be conducted on the earlier of a) when the final subject enrolled 
reaches 12 months post-implant or b) all subjects enrolled in the initial 36 month accrual period 
have reached 12 months post-implant. 
4.2.1. 
Primary Endpoints 
Safety: 
● 
Incidence of HAV aneurysm formation (true or pseudo) 
● 
Anastomotic bleeding or spontaneous rupture 
● 
HAV infection 
● 
HAV removal 
● 
Significant local inflammation at the HAV implantation site  
● 
Frequency and severity of adverse events 
Efficacy: 
● 
HAV patency rates (primary, primary assisted, and secondary patency rate)  
● 
Hemodynamically significant stenosis (>70% by duplex ultrasound criteria)  
4.2.2. 
Secondary Endpoints 
Safety: 
● 
Change from baseline in PRA  
● 
Change from baseline in hematology, coagulation, and clinical chemistry parameters 

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Efficacy: 
● 
HAV interventions  
● 
Patient reported PAD symptoms (VascuQol) 
● 
ABI 
● 
6 minute walk test 
● 
HAV remodeling at Months 1 (Day 29), 6 and 12 by CT angiography and US 
4.2.3. 
Long Term Endpoints (post Month 12 through Month 60) 
● HAV interventions 
● Evidence of aneurysmal dilatation or stenosis of the HAV on routine clinical duplex 
US 
● Primary, primary assisted, and secondary patency at 18, 24, 30, 36, 42, 48, 54 and 
60 months 
● Limb salvage/amputation at 18, 24, 36, 48, and 60 months, for all subjects who have 
not died, withdrawn, or been lost to follow-up. 
● Incidence of surgical revascularization of the implanted limb, at the level of the HAV 
or distal to HAV, for all patients who have not died, withdrawn, or been lost to 
follow-up. 
● VascuQol PAD symptom assessment consists of 25 questions.  The total score and 
the 5 domain scores (Activity, Symptom, Pain, Emotional, and Social) will be 
recorded in the clinical database, at 18, 24, 36, 48 and 60 months, for all patients 
who have not died, withdrawn, or been lost to follow-up.   
4.3. 
Duration of Study Participation 
For an individual subject, the expected duration of active study participation is approximately 61 
months. Enrollment (accrual) is expected to occur over 36 months. Additional data on patient and 
HAV status will be collected at 6 month intervals through 60 months after HAV implantation. 

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5. 
STUDY POPULATION 
5.1. 
Description of the Study Population 
The study population will consist of 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. 
5.1.1. 
Patient Inclusion Criteria 
1. Patients with disabling symptomatic peripheral arterial disease  
a. Rutherford stage 4 or 5 who require femoro-popliteal bypass surgery or 
b. Rutherford stage 3 with severe claudication (less than 50 yards AND causing 
severe impairment of ability to work or undertake social activities) 
2. ABI ≤ 0.6 in the study leg 
3. Patient has failed adequate medical therapy which included 
a. Exercise program 
b. Smoking cessation therapy 
c. Control of diabetes, hypertension and dyslipidemias 
d. Antiplatelet therapy 
4. Preoperative angiography or CT angiography shows superficial femoral artery occlusion 
AND required Humacyte HAV length of ≤ 38 cm. This imaging may have been conducted 
up to 6 months prior to study entry (Day 1) 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 ≥ 10 g/dL and platelet count ≥ 100,000/mm3 at screening  

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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 international 
normalized ratio (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 
5.1.2. 
Patient Exclusion Criteria  
1. Limb at high risk of amputation (SVS WIfI [Society for Vascular Surgery: Wound, 
Ischemia, and foot Infection] stage 4) 
2. Recent clinically significant trauma to the limb receiving the HAV 
3. Severe active infection (SVS foot infection grade 3) in the limb receiving the HAV  
4. Distal anastomosis planned to a below the knee artery 
5. History or evidence of severe cardiac disease (New York Heart Association [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 < 45 mL/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. Acquired immunodeficiency syndrome (AIDS) / human immunodeficiency virus (HIV) 
infection 
12. Documented hypercoagulable state as defined as either: 
a) a biochemical diagnosis (e.g. Factor V Leiden, Protein C deficiency, etc.)  - OR –  
b) 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 limb 
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 

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17. Active autoimmune disease – symptomatic or requiring ongoing drug therapy 
18. Active local or systemic infection (white blood cells [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 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.) 

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6. 
INVESTIGATIONAL MEDICINAL PRODUCT 
Additional information on the manufacturing process and testing of the IMP is provided in the 
Investigator Brochure. 
6.1. 
Product Description 
The investigational medicinal product (IMP) is a Humacyte human acellular vessel (HAV), which 
is a tissue-engineered vascular prosthesis for arterial bypass in patients with peripheral arterial 
disease. It is a sterile, non-pyrogenic acellular tubular vessel composed of human collagen types 
I and III and other extracellular matrix proteins, including fibronectin and vitronectin. The vessel 
is 6 mm in diameter and approximately 42 cm in length. The product is supplied on a silicone 
mandrel immersed in normal physiological saline in a sealed and labeled container. 
There is no placebo or comparator control group in this study.  
6.2. 
Manufacturer of the IMP 
The HAV is manufactured by: 
 
AlloSource 
 
6278 S. Troy Circle 
 
Centennial, CO 80111 USA 
Traceability of the HAV during and after the clinical investigation will be achieved by the 
assignment of lot numbers. A unique identifying lot number will be assigned to each vessel. 
6.3. 
Packaging, Storage, and Labeling 
Packaging: Each HAV is contained in a sealed, flexible plastic primary container closure system 
that was developed by Humacyte. The system meets container/closure requirements to maintain 
sterility as well as product and fluid integrity. The vessel is contained inside the system in a fixed 
manner, immersed in a sterile, phosphate buffered saline. The total volume of the storage solution 
is approximately 300 mL. 
Storage: The product is shipped under controlled conditions to maintain temperature at 4ºC 
(range: 2 – 10ºC). The product should be stored in a refrigerator that maintains this temperature 
range. The HAV MUST NOT be allowed to freeze. 
Labeling: The IMP will be labeled according to applicable guidelines and relevant regulatory 
agency requirements. A tamper proof label affixed to the secondary container will be used to 
ensure that the product is not compromised prior to use. 

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6.4. 
Implantation of the Humacyte human acellular vessel (HAV) 
The Humacyte HAV is implanted using standard vascular surgical techniques similar to placement 
of standard peripheral vascular prostheses (see study manual for details).  
Tunneling of the HAV must be performed using a sheathed tunneler. During tunneling, the HAV 
should be handled by pulling on the Dacron cuff (see study manual for details) 
After placement, HAV patency and integrity are checked by pressurizing the HAV. Prior to 
completion of surgery angiography is performed to confirm adequacy of the HAV anastomoses, 
HAV patency and peripheral runoff. The surgical site is closed using standard techniques. 
Implantation of the HAV will be undertaken by qualified vascular surgeons experienced in 
peripheral arterial bypass surgery. 
6.5. 
IMP Accountability Procedures 
Documentation of receipt, dispensing, and return of all IMP must be maintained by the Principal 
Investigator or his/her designee. It is the Principal Investigator’s responsibility to ensure that all 
IMPs are kept in a secure location, with access limited to individuals authorized by the Principal 
Investigator. The product will be shipped with the IMP Receipt Form. Once signed, the original 
IMP Form should be returned to Humacyte, and a copy will be maintained in the Principal 
Investigator’s Files. The IMP Accountability Log will be used to account for all IMP received, 
dispensed, and returned and must be maintained by the site until the conclusion of the study, at 
which time the original will be retrieved by Humacyte or their authorized designee and a copy kept 
at the site. Following accountability of the IMP by Humacyte or their authorized designee, all 
unused IMP will be returned to Humacyte. 
6.6. 
Assessment of Patient Compliance with IMP 
Not applicable. 
6.7. 
Prior and Concomitant Medications 
Prior medications are defined as all prescription medications or non-prescription aspirin taken 
within 7 days (whether continuing or not) prior to Day 1. All prior and concomitant medications 
(including immediately pre-surgery and post-surgery medications) must be listed in the patient’s 
medical record and recorded on the electronic case report form (eCRF). Drugs used during 
anesthesia should be recorded in the anesthesia records but should not be transcribed into the 

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eCRF. Patients should be questioned at each study visit concerning any new medications or 
changes in current medications. Note: particular attention should be made to identify the use 
of antithrombotic or antiplatelet agents (e.g., aspirin, clopidogrel, prasugrel, direct 
thrombin inhibitors, factor Xa inhibitors, or vitamin K antagonists). 
For each medication taken, the following information will be collected: 
● Medication generic name / components of combination product 
● Dose 
● Route of administration 
● Frequency of administration 
● Date started 
● Date stopped 
● Indication for use 
6.8. 
Essential, Precautionary and Prohibited Medications  
6.8.1. 
Essential Medications 
All patients should receive both antibiotic and antithrombotic prophylaxis in conjunction with HAV 
implantation: 
Antibiotic prophylaxis:  
● 
All patients must have at least 1 day of antibiotic prophylaxis in accordance with local 
hospital guidelines. Longer antibiotic prophylaxis is at the discretion of the 
investigator.  
Antithrombotic prophylaxis: 
● 
Intraoperative heparin: up to 150 IU/kg unfractionated heparin during surgery. 
● 
Further measures to prevent venous thromboembolism are at the discretion of the 
investigator and may include low molecular weight heparin (LMWH). 
● 
If antiplatelet therapy was not ongoing at the time of surgery, it should be commenced 
as soon as possible post operatively. Antiplatelet therapy (usually dual therapy with 
aspirin 81 to 325 mg and clopidogrel 75 mg daily) should continue long term while the 
HAV is in place. Choice of an alternative antiplatelet regimen if the patient is unable 
to tolerate aspirin or clopidogrel is at the discretion of the investigator 

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6.8.2. 
Restricted Medications  
Vitamin K antagonists, antiplatelet agents other than aspirin and clopidogrel, direct thrombin 
inhibitors and factor Xa inhibitors (e.g., dabigatran, apixaban and rivaroxaban) should be avoided 
unless essential for treatment of a medical condition arising postoperatively. In that case, 
consideration should be given to modification or cessation of antiplatelet therapy. Antiplatelet 
therapy should be restarted on cessation of these anticoagulant drugs. 

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7. 
STUDY PROCEDURES / EVALUATIONS 
7.1. 
Clinical Evaluations Through Month 12 
● Medical History: at screening and Day 1, from patient interview and medical records 
covering relevant past medical history with particular reference to peripheral arterial 
disease, prior surgical or percutaneous procedures for PAD, other cardiovascular 
disease and concurrent medical conditions. Failure of optimum medical therapy for 
PAD should be documented. 
● Smoking history and smoking cessation therapy: at screening and Day 1 
● PAD symptoms assessment: at screening and all follow up visits from Day 29 onward 
through Month 12 using the VascuQol instrument (Morgan MBF et al 2001) 
● Review of medications: at all study visits; prescription medication and non-prescription 
aspirin from Day -7 onward (see Section 6.7). Particular attention should be paid to the 
identification of over-the-counter (OTC) medications containing aspirin. 
● Physical Exam: full exam at screening and Month 12 visit or final study visit for early 
termination (ET). Focused vascular clinical examination of the operative limb (including 
any ischemic lesions) and HAV at all post-operative visits; physical exam for 
lymphadenopathy at Day 5 and Day 29; additional clinical exam as needed to evaluate 
AEs. 
● ABI (supine after 5 minute rest): at screening and all follow up visits from Day 29 onward 
through Month 12 
● 6 minute walk test: at screening and at Months 3 and 12 
● Vital signs (temperature, heart rate and sitting blood pressure): at screening and all 
subsequent study visits through Month 12 
● Adverse events: post-operatively on Day 1 and all subsequent study visits; the patient 
will be asked a general question about his/her health and for any HAV problems since 
the previous visit. 
● Angiography / CT angiography: this is a standard part of the pre-operative assessment 
of PAD patients. Patients should not be considered for the study unless results of a 
recent (within the 6 months prior to the screening visit and with no significant clinical 
deterioration subsequently) study are available.  
● Vein mapping: this is a standard part of the pre-operative assessment of PAD patients. 
Patients should not be considered for the study unless results of a recent (within the 6 
months prior to the screening visit) are available and indicate the absence of a suitable 
conduit for autologous vein bypass grafting. 
● CT angiography to assess HAV anatomy at Day 29 and Months 6 and 12  
● Intraoperative angiography to assess anastomotic anatomy, patency and runoff  

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● Clinical duplex ultrasound: clinical assessment at all postoperative visits from Day 29 
through Month 12 to assess HAV patency, mid HAV diameter and flow rate. The full 
length of the HAV should be imaged at each assessment to monitor for aneurysm 
development. 
● High resolution duplex ultrasound intra-operatively and at Months 3, 6 and 12  
● Endothelium-dependent, flow-mediated vasodilatation assessed by ultrasound 
(selected patients only at Day 29 and Month 12) 
● Electrocardiogram (ECG; 12-lead): at screening  
● Documentation of HAV interventions, surgical procedures and any complications 
immediately postoperatively through Month 12 
7.2. 
Clinical Evaluations in Long Term Follow Up (Post Month 12 
to Month 60) 
● Focused vascular clinical exam of operative limb 
● ABI (supine after 5 minute rest) 
● SAEs associated with the HAV 
● Events of Special Interest as defined in Section 8.4  
● Documentation of HAV interventions 
● PAD symptoms assessment: VascuQol instrument (Morgan MBF et al 2001) 
● Clinical duplex ultrasound: clinical assessment at all long term follow up visits from 
Month 18 onward through Month 54 to assess HAV patency, mid HAV diameter and 
flow rate. The full length of the HAV should be imaged at each assessment to monitor 
for aneurysm development. 
● CT angiography to assess HAV anatomy at Month 60 
7.3. 
Laboratory Evaluations 
7.3.1. 
Clinical and Research Laboratory Evaluations and Specimen Collection 
The following parameters will be measured at screening and Month 6: 
● 
Hematology: hemoglobin, hematocrit, red blood cells (RBC), WBC with differential, 
platelet count  
● 
Clinical chemistry: sodium, potassium, calcium, blood urea nitrogen (BUN), creatinine, 
albumin, total bilirubin, glucose (non-fasting) 
● 
Urine or serum human chorionic gonadotropin (HCG) pregnancy test for WOCBP 
defined as not sterile or not > 1 year postmenopausal (screening only) 
● 
Coagulation: INR and activated partial thromboplastin time (aPTT) 

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● 
HbA1c (Screening only) 
● 
PRA 
All laboratory tests (except assay of PRA) will be conducted at certified hospital laboratories. 
Routine monitoring, maintenance or calibration of laboratory equipment is required per local site 
procedures. Samples for analysis of PRA will be shipped to Humacyte for analysis at a central 
laboratory. 
Details concerning sample collection and processing can be found in the Study Manual. 
7.4. 
Imaging Evaluations 
7.4.1. 
CT angiography 
At Day 29 and Months 6, 12, and 60 CT angiography of the Humacyte HAV will be obtained using 
a multi-detector (≥ 16-slice detector) CT scanner. CT angiography images of the entire HAV will 
be acquired in a craniocaudal direction with a slice thickness of ≤ 1 mm using a bolus-tracking 
technique to optimize contrast opacification with automated injection of iodinated contrast (iohexol 
or similar).  
Details of the procedure and the method of assessment of the images by a core lab will be given 
in a separate Imaging Procedures Manual. 
7.4.2. 
Duplex ultrasound 
Clinical duplex ultrasound examinations will be performed at Day 29 and Months 3, 6, 9,  12, 18, 
24, 30, 36, 42, 48, and 54 and will follow standard bypass graft imaging protocols, including 
B-mode, power duplex and color duplex ultrasound imaging of the HAV with velocity spectral 
waveform analysis. The purpose of this clinical duplex ultrasound surveillance is to detect HAV 
stenosis and aneurysm development. 
High-resolution duplex ultrasound imaging will be performed at Day 1 and Months 3, 6 and 12 to 
investigate the structural, mechanical and functional characteristics of the Humacyte HAV. This 
protocol will involve standard vascular lab imaging equipment and can be accomplished 
immediately following the clinical scan. The estimated additional scanning time is 15-20 minutes. 
A subset of patients will also undergo endothelium-dependent flow-mediated vasodilation 
(EDFMV) testing of the HAV at Day 29 and Month 12. HAV diameter, time-averaged blood flow 
velocity and mean blood flow will be measured at baseline and during reactive hyperemia. The 

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percent change in HAV diameter during reactive hyperemia represents flow-mediated 
vasodilation, considered evidence of endothelial function. 
Details of the procedure and the method of assessment of the images by a core lab will be given 
in a separate Imaging Procedures Manual.  
7.5. 
Study Schedule 
7.5.1. 
Screening (Day -35 to Day -1) 
Potential study participants who are being considered for femoro-popliteal bypass surgery will be 
informed about the study and invited to participate. After explanation of the potential risks and 
benefits of the HAV and of the study procedures, written informed consent will be obtained. No 
study specific procedures may be performed prior to patient consent. 
The following assessments will be performed within 35 days prior to surgery (Day 1): 
● Informed consent 
● Medical history 
● Review of medical therapy for PAD (exercise program; antiplatelet therapy; 
management of diabetes, hypertension and dyslipidemias to current guidelines; 
smoking history and assistance with smoking cessation) 
● PAD symptoms (VascuQol) 
● Prior and concomitant medications (all prescription medications plus non-prescription 
aspirin)  
● Full physical examination including number, size and location of ischemic lesions on 
the intended implant leg 
● Evaluation of inclusion/exclusion criteria 
● ABI – measured with patient supine after 5 minutes rest 
● 6 minute walk test 
● Vital signs (blood pressure, heart rate, temperature – oral, axillary or tympanic) 
● Review of recent angiography / CT angiography (within previous 6 months and no 
significant clinical change since then) to confirm length of stenosis / occlusion of 
superficial femoral artery, length of required HAV and patency of run-off vessels 
● Review of vein mapping to confirm absence of suitable autologous conduit 
● ECG (12-lead) 

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● Laboratory testing 
▪ 
Hematology: full blood count and differential 
▪ 
Clinical chemistry; sodium, potassium, calcium, BUN, creatinine, albumin, total 
bilirubin, glucose (non-fasting) 
▪ 
Urine or serum HCG pregnancy test for WOCBP  
▪ 
Coagulation tests: aPTT and INR 
▪ 
HbA1c 
▪ 
PRA (sample to be taken for later analysis) 
7.5.2. 
Enrollment – Day 1 (HAV Implantation)  
Prior to surgery the following assessments will be performed: 
● Medical history (change from screening) 
● Medication history (change from screening) 
● Physical exam including surgical site (and HAV patency), number, size and location of 
ischemic lesions on the implant limb, and to evaluate any AEs 
● Confirmation of eligibility (all screening results reviewed) 
● Vital signs (heart rate, blood pressure, temperature – oral, axillary or tympanic) 
● Adverse events 
Intraoperative Procedures: 
● Implantation of HAV and documentation of surgical procedure, any complications (e.g., 
prolonged oozing at anastomoses), and interventions 
● Confirmation of adequacy of anastomoses, patency and run-off by intraoperative 
angiography 
● High-resolution duplex ultrasound of the HAV will be performed to provide a baseline for 
follow up measurements 
7.5.3. 
Follow-up Visits Day 5 through Month 12 
Day 5 (or prior to hospital discharge if earlier)  
● Review of concomitant medications   
● Physical exam including surgical site (and HAV patency); lymphadenopathy; number, 
size and location of ischemic lesions on the implant leg; and to evaluate any AEs 
● Vital signs  

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● Documentation of any HAV interventions 
● Adverse events 
Day 29 (± 4 days) 
● PAD symptoms (VascuQol) 
● Review of concomitant medications 
● Physical exam including surgical site (and HAV patency); lymphadenopathy; number, 
size and location of ischemic lesions on the implant leg; and to evaluate any AEs 
● Clinical duplex ultrasound of the HAV 
● EDFMV testing of the HAV (subset of patients) using high resolution duplex ultrasound 
● CT angiography of HAV 
● Documentation of interventions 
● ABI – supine after 5 minutes rest 
● Adverse events 
● Vital signs 
Months 3, 6 and 9 (± 14 days) 
● PAD symptoms (VascuQol) 
● Review of concomitant medications  
● Physical exam including surgical site (and HAV patency); number, size and location of 
ischemic lesions on the implant leg; and to evaluate any AEs 
● Vital signs 
● ABI – supine after 5 min rest 
● 6 minute walk test (Month 3 visit only) 
● Clinical duplex ultrasound of the HAV 
● High resolution duplex ultrasound of the HAV (Months 3 and 6 only) 
● CT angiography of HAV (Month 6 only) 
● Documentation of interventions 
● Adverse events 
● Laboratory assessments (clinical chemistry, hematology and coagulation, PRA) – all at 
Month 6 only 

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Month 12 (±14 days) and Early Termination 
● PAD symptoms (VascuQol) 
● Review of concomitant medications  
● ABI – supine after 5 min rest 
● 6 minute walk test 
● Clinical and high resolution duplex ultrasound of the HAV 
● EDFMV testing of the HAV (subset of patients) using high resolution duplex ultrasound 
● CT angiography of HAV 
● Documentation of interventions 
● Adverse events 
● Full physical exam including surgical site (and HAV patency); number, size and location 
of ischemic lesions on the implant leg; and to evaluate any AEs 
● Vital signs 
7.5.4. 
Long Term Follow Up Post Month 12 through Month 60 (± 30 days) 
The status of the patient and HAV will be ascertained every 6 months through 5 years after HAV 
implantation. 
● PAD symptoms (VascuQol)  
● ABI – supine after 5 min rest 
● Documentation of interventions 
● SAEs  
● Events of Special Interest as defined in Section 8.4 
● Physical exam of HAV surgical site and distal limb 
● Clinical duplex ultrasound of the HAV (Months 18 through Month 54) 
● CTA of operative extremity (Month 60 only) 
7.5.5. 
Early Termination Visit 
The patient may withdraw from the study at any time at his/her own discretion.  The treating 
physician may also withdraw the subject for safety reasons. If withdrawal occurs before Month 12, 
the patient will be asked to complete an early termination visit at which all assessments normally 
performed at Month 12 will be completed. If withdrawal occurs after Month 12 and prior to 

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Month 60, the patient will be asked to complete an early termination visit at which all assessments 
normally conducted during the long term follow up visits will be completed.    
The reasons for early termination should be recorded in the eCRF. 
7.5.6. 
Unscheduled Visits 
If necessary to evaluate adverse events or HAV complications, additional visits may be scheduled 
at the discretion of the investigator. At a minimum, HAV status on clinical examination and Doppler 
ultrasound and adverse events will be recorded. 
If, at any of the scheduled visits, duplex ultrasound surveillance suggests the development 
of a ≥ 50% stenosis within the HAV but immediate intervention is not required, closer follow 
up should be considered. Intervention to manage any such stenosis is at the discretion of 
the investigator taking into account the degree and rate of progression of the stenosis.  
7.6. 
Medical Care during the Study and upon Study Termination 
Optimal medical therapy should be continued during the study. This should include: 
● An exercise program 
● Smoking cessation advice and therapy 
● Management of diabetes, hypertension and dyslipidemias according to current guidelines.  
● Antiplatelet therapy (see Section 6.8.1) 
After the final study visit at Month 60, patients will not receive any further study-specific treatment. 
They will be treated by their physician in a way that is appropriate for them.  
7.7. 
Histological Examination of Resected HAV Material 
If all or part of the HAV is resected, it should, wherever possible, be retained for future histological 
examination. Instructions for preservation, storage and shipping of this material will be provided 
separately in a procedures manual. If a patient dies with an HAV in situ and it is feasible to obtain 
a fresh postmortem sample of the HAV, this should be attempted in accordance with local 
regulations. 

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8. 
SAFETY ASSESSMENTS AND ADVERSE EVENTS 
Safety of the HAV will be assessed in terms of: 
● Aneurysm formation 
● Pseudoaneurysm formation 
● Anastomotic bleeding or spontaneous rupture 
● HAV infection 
● Need for HAV removal 
● Significant inflammation at the implantation site  
● Other adverse events 
● Laboratory parameters (clinical chemistry, hematology, and coagulation) 
● Increase from baseline in PRA 
8.1. 
Adverse Event Definition 
An AE is any untoward medical occurrence in a patient administered an IMP and which does not 
necessarily have a causal relationship with the IMP. An AE can, therefore, be any unfavorable 
and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an IMP, whether or not related to the IMP. Any worsening of the 
patient’s disease under study or other medical conditions will also be considered to be an AE, 
unless it is within the normal range of disease fluctuation for that patient. 
8.2. 
Serious Adverse Event Definition 
An AE is considered “serious” if, in the view of either the investigator or Sponsor, it: 
● Results in death 
● Is life-threatening 
o The term “life-threatening” in the definition of “serious” refers to an event in which 
the patient was at immediate risk of death at the time of the event; it does not 
include an adverse event that had it occurred in a more severe form, might have 
caused death. 

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● Requires patient hospitalization or prolongation of existing hospitalization 
o This is defined as the patient being hospitalized for 24 hours or more or the 
patient’s hospital stay being prolonged for at least an additional overnight stay. 
● Requires intervention to prevent permanent damage 
● Results in persistent or significant disability/incapacity 
● Is a congenital anomaly/birth defect 
● Important Medical Events 
o For the purpose of this study, this includes any event involving the HAV that results 
in a surgical or endovascular radiological intervention. The event(s) which caused 
the procedure should be reported as an SAE.  For example: in the event of HAV 
thrombosis, the thrombosis would be considered the SAE; any associated 
stenoses (or other associated findings) that are present would be considered AEs. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting to 
the sponsor is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the patient or 
may require medical or surgical intervention to prevent one of the other outcomes listed in the 
definition above. These may also be considered to be SAEs. 
Note: Hospitalization for the surgery to implant the HAV is not a SAE. However, prolongation of 
the initial hospitalization due to an AE will be considered a SAE. 
8.3. 
Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is any adverse drug reaction that is 
serious (as defined in Section 8.2), unexpected (is not listed in the IB or is not listed at the 
specificity or severity that has been observed) and suspected (meaning there is a reasonable 
possibility that the IMP caused the adverse event).  
8.4. 
Events of Special Interest 
Events of Special Interest are: 
● HAV occlusion (thrombosis) 
● HAV spontaneous rupture 

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o Iatrogenic injuries are not an Event of Special Interest and should be reported as 
an AE 
● HAV infection 
● HAV abandonment 
● HAV aneurysm  
● HAV pseudoaneurysm 
● HAV excision (partial or complete) 
8.5. 
Reporting of Adverse Events 
At each evaluation, the investigator will determine whether any AEs have occurred. The patient 
will be questioned in a general way and no specific symptoms will be suggested. If any AEs have 
occurred, they should be documented in the patient’s medical chart and recorded on the AE pages 
of the eCRF. If known, the diagnosis should be recorded in preference to the listing of individual 
signs and symptoms. All serious adverse events (SAEs should be reported to the Safety Contract 
Research Organization (CRO) within 24 hours from the time the investigator or study personnel 
first become aware of the event. 
AE reporting begins from implantation of the HAV (the moment the patient undergoes anesthesia) 
and ends at the conclusion of the Month 12 or ET visit unless an unresolved AE is still being 
followed.    
During the long term follow up period from post Month 12 through Month 60, only the following 
will be reported by the investigator: 
● All SAEs  
● All Events of Special Interest (Section 8.4) 
8.5.1. 
Criteria for Determining Causal Relationship to the HAV and Criteria for 
Determining Causal Relationship to the Index Surgical Procedure 
The criteria for determining the causal relationship of an AE with the HAV are presented in the 
table below. A separate assessment of causal relationship of an AE to the index surgical 
procedure is required as well using the same criteria and definitions presented in the table below. 
Please note that causal relationship to procedure only refers to the index surgical procedure in 
which the HAV was initially implanted. 

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Causal Relationship 
to the IP 
Criteria for Determining Causal Relationship 
Definitely Related 
There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, 
including an abnormal laboratory test result, occurs in a plausible 
time relationship to surgical placement of the HAV and cannot be 
explained by concurrent disease or other devices, drugs, or 
chemicals. 
Possibly Related 
There is some evidence to suggest a causal relationship (e.g., the 
event occurred within a reasonable time after the surgical placement 
of the HAV). However, the influence of other factors may have 
contributed to the event (e.g., the subject’s clinical condition, other 
concomitant medications). Although an adverse event may rate only 
as “possible” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to certain as appropriate. 
Unlikely Related 
A clinical event, including an abnormal laboratory test result, whose 
temporal relationship makes a causal relationship improbable (e.g., 
the event did not occur within a reasonable time after surgical 
placement of the HAV) and in which other drugs or chemicals or 
underlying disease provide plausible explanations (e.g., the subject’s 
clinical condition, other concomitant treatments). 
Not Related 
A clinical event, including an abnormal laboratory test result, which 
occurs when the HAV was not implanted; or, another cause is 
obvious and in which there is sufficient information that the etiology 
of the event is not related to the HAV. 
The sponsor will make the final determination of causality for the purposes of reporting to the 
regulatory authorities and to the Principal Investigators.  

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8.5.2. 
Criteria for Defining the Severity of an Adverse Event 
Severity of adverse events, including abnormal clinical laboratory values, will be assessed 
according to the criteria below and entered in the eCRF: 
Grade 
Severity Assessment Standard 
1-Mild 
Events require minimal or no treatment and do not interfere 
with the subject’s daily activities. 
2-Moderate 
Events result in a low level of inconvenience or concern with 
the therapeutic measures. Moderate events may cause 
some interference with functioning. 
3-Severe 
Events interrupt a subject’s usual daily activity and may 
require systemic drug therapy or other treatment. Severe 
events are usually incapacitating. 
4-Life-threatening 
Any adverse event that places the subject or participant, in 
the view of the investigator, at immediate risk of death from 
the reaction as it occurred, i.e., it does not include a reaction 
that, had it occurred in a more severe form, might have 
caused death. 
5-Death 
Death related to AE. 
8.5.3. 
Reporting of Action Taken to Resolve AE 
● None 
● Lab tests / further evaluation 
● Treatment required (specify if hospitalized) 
● Patient withdrawn from study 
● Other (specify) 
8.5.4. 
Reporting the Outcome of the AE 
● Recovered, with sequelae 
● Recovered, without sequelae 
● Ongoing 
● Death 

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● Lost to follow-up 
8.5.5. 
Reporting Serious Adverse Events 
The urgency for reporting SAEs is 4-fold: (1) to facilitate discussion (and implementation, if 
necessary) by the sponsor and the investigator of appropriate follow-up measures, (2) to facilitate 
investigator reporting of unanticipated problems involving risk to human subjects to the 
institutional review board (IRB), (3) to facilitate the sponsor’s rapid dissemination of information 
regarding AEs to other investigators/sites in a multi-center study, and (4) to enable the sponsor 
to fulfill the reporting requirements to the appropriate regulatory authority. 
Any SAE that occurs through Month 60, whether or not causally related to the IMP, must 
be reported by the investigator or designee to the Safety CRO within 24 hours of learning 
of its occurrence. This applies also to any AE that could affect the safety of the study 
participants or the conduct of the study.  
Information about an SAE will be collected and recorded on the SAE Report Form. The 
investigator must assess the relationship to the investigational product and any relevant 
procedure. 
The investigators must complete the SAE Report Form in English, and send the completed, 
signed form by fax or email (see below) IMMEDIATELY (at latest within 24 hours) after 
becoming aware of the SAE.  
Copies of relevant medical records (e.g., admission and/or discharge summary, laboratory reports 
and autopsy report), may also be submitted with the SAE form to clarify the circumstances 
surrounding the SAE(s). The entire medical records should NOT be sent with the SAE form.  
Atlantic Research Group, Inc. 
Drug Safety Department 
Fax: +1-866-851-9318 
Email: Safety@atlanticresearchgroup.com 
Phone: +1-888-619-3216 
The investigator will be requested to supply as much detailed information as possible regarding 
the SAE that is available at the time of the initial contact. The investigator should also complete 
missing or requested information and submit follow-up reports until the SAE has resolved or, in 
the case of permanent impairment, until the SAE has stabilized.  

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It is the responsibility of each Principal Investigator to promptly notify his/her IRB of all SAEs that 
are received by the Sponsor or designee and that occur at his/her institution in accordance with 
institutional practices.  
The Safety CRO will inform the sponsor about all SAEs within 1 business day after receipt of the 
respective report from the investigator. 
8.5.6. 
Reporting of Events of Special Interest 
Events of Special Interest are defined in Section 8.4 and should be reported to the Safety CRO 
within 24 hours of learning of its occurrence.  For each of these events detailed surgical notes 
(with illustrative diagram), including reason for and outcome of any intervention or abandonment, 
should be completed within 48 hours and uploaded to the clinical database. 
Detailed information about the occurrence and treatment/intervention for these events will be 
collected throughout the study up to 5 years post HAV implant.  This information will include the 
following: 
● Summarized surgical notes, including a simplified anatomical diagram showing where 
angioplasties, stents, or revisions have been performed (using intervention worksheet 
provided) 
● Need for hospitalization (number of nights) 
● Need for antibiotics (in the case of HAV-related infections) 
8.5.7. 
Follow-Up of Adverse Events 
If any AEs are present when a subject completes 1 year post implant (Month 12) or ET, if earlier, 
or if a subject is withdrawn from the study, the subject will be re-evaluated within an appropriate 
period of time. At the investigator’s discretion, minor AEs can be re-evaluated via telephone and 
documented. If the AE has still not resolved, additional follow-up will be performed as appropriate. 
The investigator or his designee should make every effort to contact the subject until the AE has 
resolved or stabilized or the medical monitor and investigator agree that further follow-up is not 
necessary. This should be documented in the subject’s medical records. 
8.6. 
 Reporting of Pregnancy  
If a study participant becomes pregnant during study participation, the participant will be 
withdrawn from the study and the event will be recorded as an adverse event in the eCRF. The 

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site will also collect information about the pregnancy on the Pregnancy & Outcome Report Form 
(PORF), which must be submitted to the Safety CRO within 1 business day of completion. 
Complications experienced during the pregnancy will be recorded as AEs in the eCRF.  
The participant will be asked to report the outcome of the pregnancy to the site. The site should 
collect the available outcome information and provide an updated PORF to the Safety CRO within 
1 business day of receipt. If there is a congenital anomaly in the infant, this will be recorded as a 
SAE in the data forms for the mother (i.e., the study participant). 
Partner pregnancies do not need to be reported. 
8.7. 
 Data Monitoring Committee 
A Data Monitoring Committee (DMC) will review safety on an ongoing basis and provide 
recommendations about stopping, continuing or otherwise modifying the study. The DMC consists 
of individuals who are not directly involved in the conduct of the study. A charter describes the 
roles and responsibilities of the DMC. Responsibilities of the DMC will include review of aggregate 
safety data from other studies in the HAV clinical development program.  
8.8. 
 Interim Analysis and Stopping Criteria 
This is a Phase 2 study with no formal interim analysis. Periodic reviews of safety data will be 
undertaken by the DMC with particular attention to events that might indicate structural failure of 
the HAV. Events that might have implications for already implanted HAVs and their possible 
removal - such as aneurysm formation (true or pseudo) or spontaneous rupture - will trigger a 
referral of the event urgently for DMC review  
The DMC may recommend modification or early termination of the study for safety reasons. 

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9. 
STATISTICAL CONSIDERATIONS 
This is a prospective, open label, single treatment arm, multicenter pilot 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. 
Endpoints will be assessed over a period of up to 60 months after HAV implantation. The primary 
analysis of the study will be conducted on the earlier of a) when the final subject enrolled reaches 
12 months post-implant or b) all subjects enrolled in the initial 36 month accrual period have 
reached 12 months post-implant. Details of data handling and planned descriptive statistics are 
given in the Statistical Analysis Plan. 
9.1. 
Analysis Population 
All patients who receive an HAV will be included in the analyses. For discontinued or withdrawn 
patients, all available data will be included in the safety and efficacy analyses.  
9.2. 
Safety Analyses 
Safety analyses will be performed on all patients who have an HAV implanted when the final 
patient enrolled reaches 12 months post-implant 
Incidence of HAV aneurysm formation (true or pseudo), anastomotic bleeding or spontaneous 
rupture, HAV infection, HAV removal, and significant local inflammation at the HAV implantation 
site will be separately tabulated and listed. 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terms. 
Adverse events will be listed and summarized by system organ class, preferred term, incidence, 
severity, and duration. HAV complications will be listed in terms of incidence, severity, and (where 
appropriate) time to onset and duration. Serious adverse events will be summarized separately. 
Any premature discontinuations due to adverse events and deaths will be listed and summarized. 
Laboratory data, including PRA, will be listed and summarized using appropriate descriptive 
statistics at each visit and for the absolute change from baseline values for all post-surgery visits. 
The closest non-missing values prior to surgery on Day 1 will be used as baseline values. 
9.3. 
 Efficacy Analyses 
Primary, primary assisted, and secondary patency rates of the HAV at Month 12 and at all other 
post-surgery visits with evaluation of patency will be described.  

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Primary patency is defined as the functional patency until any type of intervention; primary 
assisted patency is defined as an HAV still working without thrombosis; secondary patency is 
defined as the functional patency, with or without preceding successful interventional or surgical 
procedures to maintain or reestablish patency, until either final failure or the access is abandoned. 
Early discontinued patients prior to the visit of interest will be determined as being non-patent 
irrespective of the reason for discontinuation. 
The rate and type of interventions needed to maintain / restore patency in the HAV will be 
descriptively tabulated.  
The absolute change from baseline (Day 1) values to all post-surgery visits of duplex ultrasound 
parameters will be summarized. Summary statistics will also be provided at each time point.  
The methods and endpoints regarding the efficacy parameters employed in this study are 
consistent with current clinical practice and are meaningful to the research community. Every 
attempt has been made to minimize the variability on the part of the surgeon when using this 
product. The results of this study will be used to determine the sample size of subsequent clinical 
studies. 
9.4. 
Other Analyses 
All clinical parameters will be listed for all patients treated at each study visit. Descriptive statistics 
will be summarized for continuous outcomes such as age and BMI. If necessary, number and 
percentage of patients will be reported for categorical outcomes. 
9.5. 
Sample Size Rationale 
Up to 25 patients will be recruited into the study. As limited data evaluating the use of HAV to 
treat PAD are available, this Phase 2 study was designed to provide preliminary evidence of 
safety and efficacy.  
The study is not powered to assess the efficacy of the HAV. 
9.6. 
Interim analyses 
There is no formal interim analysis. 

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10. 
STUDY MANAGEMENT AND DATA COLLECTION 
10.1. 
Ethical Conduct of the Trial 
This study will be conducted according to the protocol; 21 CFR Parts 11, 50, 54, 56, and 312; the 
World Medical Association Declaration of Helsinki (Appendix II) and Good Clinical Practice (GCP). 
Each investigator will conduct the trial according to applicable local or regional regulatory 
requirements. 
10.2. 
Institutional Review Board 
IRBs must be constituted according to the applicable state and federal requirements, including 
International Conference on Harmonization (ICH) GCP. 
It is the responsibility of each investigator to submit the protocol, Investigator Brochure, subject 
informed consent, subject recruitment materials (if applicable), and other documentation as 
required by the IRB to his/her IRB for review and approval.  A copy of the written approval must 
be provided to the CRO. The documentation should clearly mention the approval/favorable 
opinion of the protocol, the subject informed consent form, and subject recruitment materials (if 
applicable), including respective version dates.  The written approval must be obtained from the 
IRBs and provided to the CRO prior to the release of clinical study supplies to the investigational 
site and commencement of the study. If any member of the IRB has direct participation in this 
trial, written notification regarding his or her abstinence from voting must also be obtained. 
Each investigator must adhere to all requirements stipulated by his/her respective IRB. This 
includes notification to the IRB regarding protocol amendments, updates to the subject informed 
consent, recruitment materials intended for viewing by subjects, investigational new drug safety 
reports, SAEs and unexpected AEs, reports and updates regarding the ongoing review of the trial 
at intervals specified by the respective IRB, and submission of final study reports and summaries 
to the IRB. 
10.3. 
Subject Informed Consent 
Prior to any study procedures being performed, subjects and persons conducting the consent 
discussion will be required to sign and date the IRB-approved informed consent, and each subject 
will be given a copy. In addition, this information should be recorded in the subject’s medical 
record (i.e., source document). 
The written consent document will embody the elements of informed consent as described in the 
World Medical Association Declaration of Helsinki, 21 CFR Part 50.25, ICH E6 guideline (GCP), 
and in accordance with any local regulations. The investigator is responsible for the preparation, 
content, and IRB approval of the informed consent document. The consent form must be 
approved by the site’s IRB and be acceptable to Humacyte. 

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The consent form must be written in a language fully comprehensible to the prospective subject. 
The investigator or designee shall give the subject adequate opportunity to read it before it is 
signed and dated. Information should be given in both oral and written form whenever possible 
and in the manner deemed appropriate by the IRB. Subjects must be given ample opportunity to 
inquire about details of the study. 
10.4. 
Amendments to the Protocol 
An amendment must be agreed to in writing by Humacyte and submitted to the Food and Drug 
Administration (FDA) and approved by IRBs before the amendment can be implemented. Written 
approval of a protocol amendment is not required prior to implementation of changes to the 
protocol which eliminate an immediate hazard to the study patient; however, approval must be 
obtained as soon as possible thereafter. Any agreed amendments must also be signed by the 
Principal Investigator. 
10.5. 
Study Initiation 
The investigator must not enroll any patients prior to attendance at the Investigator Meeting or 
the completion of a formal site initiation visit conducted by the CRO. These meetings will include 
a detailed review of the study protocol and eCRF pages. The Principal Investigator will not be 
supplied with IMP until all necessary pre-study requirements have been completed and essential 
signed documents provided to the CRO. 
10.6. 
Study Monitoring 
It is the responsibility of the investigator to ensure that the study is conducted in accordance with 
the protocol, GCP, applicable regulatory requirements, and the currently approved Declaration of 
Helsinki, and that valid data are entered into the eCRF. 
To achieve this objective, the monitor’s duties are to ensure the maintenance of complete, legible, 
well-organized, and easily retrievable data. The monitor will review the protocol with the 
investigator. In addition, the monitor will explain the investigator’s reporting responsibilities and 
all applicable regulations concerning the clinical evaluation of the IMP. 
The investigator will permit representatives of Humacyte and the CRO to monitor the study as 
frequently as Humacyte or the CRO deem necessary to determine that data recording and 
protocol adherence are satisfactory. The eCRF data and related source documents will be 
reviewed in detail by the monitor at each visit, in accordance with relevant standard operating 
procedures (SOPs) and ICH GCP regulations. This includes results of tests performed as a 
requirement for participation in this study and any other medical records required to confirm 
information contained in the eCRF such as past medical history and secondary diagnoses. The 
investigator and his/her staff will be expected to cooperate with the monitor and provide any 
missing information whenever possible. 

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All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
10.7. 
Case Report Form  
An eCRF will be used for this study. The data will be entered into the eCRF in a timely manner 
on an ongoing basis.  
The investigator is responsible for ensuring that data are properly recorded on each patient’s 
eCRF and related documents. An investigator who has signed the protocol signature page should 
personally sign the eCRFs in accordance with the procedure described in the eCRF completion 
guidelines to ensure that the observations and findings are correct and complete.  
For data handled by the CRO, eCRF data and some or all of the study-related data will be 
managed and stored electronically in the CRO’s database system. Validated data will 
subsequently be transferred to the sponsor. 
10.8. 
Verification Procedures 
It is the investigator’s obligation to ensure documentation of all relevant data in the subject’s 
medical record. The subject’s medical record will be considered the source document. The eCRF 
should not be used as the source for study information. 
The investigator will maintain a subject identification code list to enable unambiguous 
identification of the subjects (subject names and corresponding subject numbers). The subject 
identification code list is an essential document and as such should be maintained according to 
the ICH GCP guidelines. 
10.9. 
Retention of Records 
All documentation pertaining to the study will be kept by Humacyte or their designee in 
accordance with ICH guidelines and US FDA regulations. 
The investigator will maintain a study file, which should be used to file the Investigator Brochure, 
protocol, and IMP records; correspondence with the IRB and Humacyte; and other study-related 
documents. 
The investigator agrees to keep records and those documents that include (but are not limited to) 
the identification of all participating subjects, medical records, study-specific source documents, 
source worksheets, all original signed and dated informed consent forms, query responses, and 
detailed records of drug disposition to enable evaluations or inspections from regulatory 
authorities and Humacyte or its designees. 
The investigator shall retain records required to be maintained under this part for a period of 
2 years following the date a marketing application is approved for the IMP for the indication for 

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which it is being investigated; or, if no application is to be filed or if the application is not approved 
for such indication, until 5 years after the investigation is discontinued. However, these documents 
should be retained for a longer period if required by the applicable regulatory requirement(s) or if 
needed by the sponsor. In addition, the investigator must make provision for the subject’s medical 
records to be kept for the same period of time. No data should be destroyed without the agreement 
of Humacyte. Humacyte will inform the investigator in writing when the trial-related records are no 
longer needed. Subject’s medical records and other original data will be archived in accordance 
with the archiving regulations or facilities of the study site.  
10.10. Protocol Deviations 
A protocol deviation is any noncompliance with the protocol or GCP requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. 
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. Although in principle protocol deviations are not permitted, under emergency 
circumstances, deviations may proceed without prior approval of the sponsor and the IRB to 
protect the rights, safety, and well-being of human subjects. 
All protocol deviations will be documented and reported by the CRO during the course of the study 
in the Monitoring Reports. All deviations will be reported to the sponsor who will agree on the 
necessary actions to be taken. 
If required per their guidelines, reports about protocol deviations must be reported to the local 
IRB. 
10.11. Insurance and Indemnity 
Insurance coverage for damages emerging from the study will be provided according to applicable 
legal requirements. During the informed consent procedure, the investigator must inform the 
patient accordingly.  
10.12. Audit 
It is the responsibility of CRO and Humacyte to perform auditing (if applicable) as part of 
implementing quality assurance. The purpose of an audit, which is independent of and separate 
from routine monitoring or quality control functions, is to evaluate trial conduct and compliance 
with the protocol, SOPs, GCPs, and the applicable regulatory requirements. The auditor and 
regulatory authorities will require authority from the investigator to have direct access to the 
subject’s medical records. 

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11. 
REPORTING 
Following completion of follow-up of all patients to the 12-month endpoint, the results will be 
evaluated by Humacyte or a designee for clinically meaningful findings. A clinical study report will 
be generated, including a summary of all available data, statistical measures, tabulated results, 
graphical results and interpretations. This report will be submitted to regulatory authorities in a 
timely manner. An addendum to the report will be generated to include data up to 60 months 
follow-up. This addendum will be submitted to regulatory authorities in a timely manner. 

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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following written standard operating procedures, the monitors will verify that the clinical trial is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable regulatory requirements. Reports of monitoring activities will 
be submitted to Humacyte in a timely manner. 
The investigational site will provide direct access to all trial related areas, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
Quality control procedures will be implemented for data entry and the generation of data quality 
control checks and will be run on the database. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 

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13. 
RESPONSIBILITIES OF THE PRINCIPAL 
INVESTIGATOR 
The role of the Principal Investigator is to implement and manage the day-to-day conduct of the 
clinical investigation as well as to ensure data integrity and the rights, safety, and well-being of 
the patients involved in the clinical investigation. 
13.1. 
Informed Consent 
The Principal Investigator shall ensure that the process for obtaining informed consent  
● includes all aspects of the clinical investigation that are relevant to the patient's decision 
to participate throughout the clinical investigation, 
● avoids any coercion or undue improper influence on, or inducement of, the patient to 
participate,  
● does not waive or appear to waive the patient's legal rights,  
● uses native non-technical language that is understandable to the patient,  
● provides ample time for the patient to read and understand the informed consent form and 
to consider participation in the clinical investigation,  
● provides the patient with a copy of the signed and dated informed consent form and any 
other written information. 
The Principal Investigator shall ensure and document appropriate training if an authorized 
designee is appointed to conduct the informed consent process. 
13.2. 
Compliance with the Protocol 
The Principal Investigator shall: 
● indicate his/her acceptance of the protocol in writing  
● conduct the clinical investigation in compliance with the protocol 
● create and maintain source documents throughout the clinical investigation and make 
them available as requested during monitoring visits or audits 
● ensure that the IMP is used solely by authorized users, and in accordance with the protocol 
and instructions for use 
● propose to the sponsor any appropriate modification(s) of the protocol 

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● refrain from implementing any modifications to the protocol without agreement from the 
sponsor, IRB, and, if required, regulatory authorities  
● document and explain any deviation from the approved protocol that occurred during the 
course of the clinical investigation 
● ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation 
● ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable 
● ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the eCRFs and in all required reports 
● maintain the clinical trial material accountability records 
● allow and support the sponsor to perform monitoring and auditing activities 
● be accessible to the monitor and respond to questions during monitoring visits 
● allow and support regulatory authorities and the IRB when performing inspection activities 
● ensure that all clinical-investigation-related records are retained as specified in this 
protocol. 
13.3. 
Medical Care of Patients 
The Principal Investigator shall: 
● provide adequate medical care to a patient during and after a patient's participation in a 
clinical investigation in the case of AEs 
● inform the patient of the nature and possible cause of any adverse events experienced  
● inform the patient of any new significant findings occurring during the clinical investigation, 
including the need for additional medical care that may be required 
● provide the patient with well-defined procedures for possible emergency situations related 
to the clinical investigation, and make the necessary arrangements for emergency 
treatment,  
● ensure that clinical records are clearly marked to indicate that the patient is enrolled in a 
particular clinical investigation 

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● inform, with the patient’s approval or when required by national regulations, the patient's 
personal physician about the patient's participation in the clinical investigation  
● make all reasonable efforts to ascertain the reason(s) for a patient's premature withdrawal 
from the clinical investigation while fully respecting the patient's rights.  
13.4. 
Safety Reporting 
The Principal Investigator shall: 
● record every adverse event together with an assessment, in accordance with Sections 8  
and 9 of this protocol, 
● report to the sponsor, without unjustified delay, all serious adverse events and medically 
significant events as specified in Sections 8 and 9 of this protocol, 
● supply the sponsor, upon sponsor’s request, with any additional information related to the 
safety reporting of a particular event. 

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14. 
SUSPENSION OR PREMATURE TERMINATION OF 
THE CLINICAL INVESTIGATION 
The sponsor may suspend or prematurely terminate either a clinical investigation in an individual 
investigation site or the entire clinical investigation for significant and documented reasons.  
A Principal Investigator, IRB, or regulatory authority may suspend or prematurely terminate 
participation in a clinical investigation at the investigation sites for which they are responsible.  
If suspicion of an unacceptable risk to patients arises during the clinical investigation, or when so 
instructed by the IRB or regulatory authorities, the sponsor shall suspend the clinical investigation 
while the risk is assessed. The sponsor shall terminate the clinical investigation if an unacceptable 
risk is confirmed.  
The sponsor shall consider terminating or suspending the participation of a particular investigation 
site or investigator in the clinical investigation if monitoring or auditing identifies serious or 
repeated deviations on the part of an investigator.  
If suspension or premature termination occurs, the terminating party shall justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication.  
If, for any reason, the sponsor suspends or prematurely terminates the investigation at an 
individual investigation site, the sponsor shall inform the responsible regulatory authority if 
required and ensure that the IRB is notified. If the suspension or premature termination was in 
the interest of safety, the sponsor shall inform all other Principal Investigators.  
If suspension or premature termination occurs,  
1. the sponsor shall remain responsible for providing resources to fulfill the obligations from 
the protocol and existing agreements for following up the patients enrolled in the clinical 
investigation, and  
2. the Principal Investigator or authorized designee shall promptly inform the enrolled 
patients at his/her investigation site, if appropriate.  
In the event that the study is discontinued, the reasons for discontinuation will be explained to the 
investigators and may be disclosed to the study participants. Humacyte will provide all information 
needed by the investigator to ensure the safety and well-being of the study participants. 

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15. 
PUBLICATION POLICY 
A Publication Committee comprising the Principal Investigator from each participating site and a 
representative of Humacyte will oversee all publication of data from this study. Prior to submitting 
for publication, presenting, using for instructional purposes, or otherwise disclosing the results of 
the study, the investigator agrees to allow the Publication Committee and Humacyte a period of 
at least 30 days (or, for abstracts, at least 5 calendar days) to review the proposed publication or 
disclosure prior to its submission for publication or other disclosure.  Publications or disclosures 
of study results shall not include other confidential information belonging to Humacyte.  If the 
proposed publication/disclosure risks Humacyte’s ability to patent any invention related to the 
study, the publication or disclosure will be modified or delayed, at the investigator's option, a 
sufficient time to allow Humacyte to seek patent protection of the invention.  For multicenter 
studies, the first publication or disclosure shall be a complete, joint multicenter publication or 
disclosure. This statement does not give Humacyte any editorial rights over the content of a 
publication or disclosure, other than to restrict the disclosure of Humacyte’s confidential 
information. If a written contract for the conduct of the study is executed which includes publication 
provisions inconsistent with this statement, then that contract's publication provisions shall apply 
rather than this statement. 

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16. 
REFERENCES 
Conte MS, Pomposelli FB et al on behalf of the Society for Vascular surgery Lower Extremity 
Guidelines Working Group. Society for Vascular Surgery practice guidelines for atherosclerotic 
occlusive disease of the lower extremities: Management of asymptomatic disease and 
claudication. J Vasc Surg 2015; 61: 2S – 41S 
Criqui MH, Denenberg JO, Langer RD, Fronek A. The epidemiology of peripheral arterial disease: 
importance of identifying the population at risk. Vasc Med. 1997; 2:221-226. 
Dahl, SL, Kypson, AP, Lawson, JH et al Readily available tissue-engineered vascular grafts. Sci 
Transl Med. 2011: 68ra9  
Dixon BS, Beck GJ, Vazquez MA et al. Effect of dipyridamole plus aspirin on hemodialysis graft 
patency. N Engl J Med 2009;360:2191-201. 
Hirsch AT, Criqui MH, Treat-Jacobson D et al. Peripheral arterial disease detection, awareness 
and treatment in primary care  JAMA. 2001;286:1317-1324. 
Kelly BS, Heffelfinger SC, Whiting JF, et al. Aggressive venous neointimal hyperplasia in a pig 
model of arteriovenous graft stenosis. Kindey Int. 2002;62(6):2272-2280. 
Kirkton RD, Santiago-Maysonet M, Lawson JH, Tente WE, Dahl SLM, Niklason LE, Prichard HL. 
Bioengineered human acellular vessels recellularize and evolve into living blood vessels after 
human implantation. Sci Transl Med. 2019 Mar 27;11(485). 
L'Heureux N, Dusserre N, Konig G, et al. Human tissue-engineered blood vessels for adult arterial 
revascularization. Nat Med 2006; 12(3):361-365. 
Mills JL et al on behalf of the Society for Vascular Surgery Lower Extremity Guidelines 
Committee. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification 
System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI). J Vasc Surg 
2013, 
Morgan MBF, Crawford T, Murrin B and Fraser SCA. Developing the vascular quality of life 
questionnaire: a new disease specific quality of life measure for use in lower limb ischemia. J 
Vasc Surg 2001; 33: 679 - 687  
Norgren L, Hiatt WR, Dormandy JA et al. Inter-Society Consensus for the Management of 
Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 45 (Suppl S): S5-67.  
Pritchard, H.L, Manson, R.J.,Dibernado, L.et al An early study on the mechanisms that allow 
tissue-engineered vascular grafts to resist vascular hyperplasia. J Cardiovasc Transl Res 2011, 
4, 674-682 

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Quint C, Kondo Y, Manson RJ,et al. Decellularized tissue-engineering blood vessel as an 
arterial conduit. Proc Natl Acad Sci USA. 108(22):9214-9, 2011. 
Roy-Chaudhury P, Kelly BS, Miller MA, et al. Venous neointimal hyperplasia in 
polytetrafluoroethylene dialysis grafts. Kidney Int. 2001;59(6):2325-2334. 
Rutherford RB1, Baker JD, Ernst C, et al Recommended standards for reports dealing with 
lower extremity ischemia: revised version. J Vasc Surg. 1997 Sep;26(3):517-38. 
 

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APPENDIX 1. HAV CLINICAL VISIT SCHEDULE 
 
Screening 
(Days -35 to -1) 
D 1 
D 5 
D 29 
+/- 4 days 
M 3 
+/- 14 days 
M 6 
+/- 14 
days 
M 9 
+/- 14 
days 
M12 /ET2 
+/- 14 days 
M18-M60 
/ET2 
+/- 30 days 
Informed consent 
X 
 
 
 
 
 
 
 
 
Medical & smoking histories; review of PAD therapy 
X 
X 
 
 
 
 
 
 
 
Review of medications 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam including ischemic lesions on implant 
leg 
X 
X1 
X1 
X1 
X1 
X1 
X1 
X 
X1 
ECG (12-lead) 
X 
 
 
 
 
 
 
 
 
Review prestudy angiography/CT angio & vein 
mapping 
X 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
 
Eligibility (inclusion/exclusion criteria) 
X 
X 
 
 
 
 
 
 
 
HAV implantation and angiography/intraop ultrasound 
 
X 
 
 
 
 
 
 
 
Documentation of surgery and any complications 
 
X 
 
 
 
 
 
 
 
Clinical chemistry; hematology; coagulation 
X 
 
 
 
 
X 
 
 
 
HbA1c 
X 
 
 
 
 
 
 
 
 
Urine or serum pregnancy test (WOCBP) 
X 
 
 
 
 
 
 
 
 
PRA  
X 
 
 
 
 
X 
 
 
 
Clinical duplex ultrasound 
 
 
 
X 
X 
X 
X 
X 
X5 
High resolution duplex ultrasound 
 
X3 
 
 
X 
X 
 
X 
 
Endothelium-dependent, flow-mediated vasodilatation 
4 
 
 
 
X 
 
 
 
X 
 
CT angiography 
 
 
 
X 
 
X 
 
X 
X6 
AEs  
 
X 
X 
X 
X 
X 
X 
X 
X7 

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Screening 
(Days -35 to -1) 
D 1 
D 5 
D 29 
+/- 4 days 
M 3 
+/- 14 days 
M 6 
+/- 14 
days 
M 9 
+/- 14 
days 
M12 /ET2 
+/- 14 days 
M18-M60 
/ET2 
+/- 30 days 
Documentation of HAV interventions 
 
X 
X 
X 
X 
X 
X 
X 
X 
PAD symptoms assessment (VascuQol) 
X 
 
 
X 
X 
X 
X 
X 
X 
ABI – supine after 5 minute rest 
X 
 
 
X 
X 
X 
X 
X 
X 
6 minute walk test 
X 
 
 
 
X 
 
 
X 
 
Patient Survival 
 
 
 
 
 
 
 
 
X 
Abbreviations: AEs, adverse events; D, day; ECG, electrocardiogram; ET, early termination; HAV, human acellular vessel; M, month; PRA, panel reactive antibody. 
NOTE: Visits should be performed using the following time windows: Screening, Day -35 to -1; Day 5 (or prior to hospital discharge, if earlier); Day 29, ± 4 days; 
Months 3,6,9,12, ± 14 days  
1 
Physical examination includes focused vascular clinical exam of HAV site (incl. patency assessment) and physical exam for lymphadenopathy (at D5 and 
D29) and to evaluate AEs. 
2 
Patients withdrawn before Month 12 should complete an ET visit that correlates with the procedures at Month 12. Patients withdrawn after Month 12 and prior 
to Month 60 should complete an ET visit that correlates with procedures post Month 12 through Month 60. 
3 
Intraoperative 
4 
Duplex ultrasound assessment of endothelium-dependent flow-mediated vasodilatation testing in a subset of patients  
5 
Clinical duplex ultrasound not required on Month 60 
6 
CT angiography only performed on Month 60. This is not required as part of an ET visit 
7 
Collection of SAEs and Events of Special Interest through Month 60  
 
If, at any of the scheduled visits through Month 12, duplex ultrasound surveillance suggests the development of a ≥ 50% 
stenosis within the HAV but immediate intervention is not required closer follow up should be considered. Intervention to 
manage any such stenosis is at the discretion of the investigator taking into account the degree and rate of progression of 
the stenosis.