A Phase 2 Assessment of Humacyte's Human Acellular Vessel in Patients Needing Vascular Access for Dialysis
Phase: PHASE2
Conditions: Renal Failure, End Stage Renal Disease, Vascular Access, Hemodialysis
Sponsor: Humacyte, Inc.

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A Phase 2 Assessment of Humacyte’s Human Acellular Vessel in 
Patients Needing Vascular Access for Dialysis   
 
  
Medicinal Product: 
 
Human Acellular Vessel (HAV) 
Study No.: 
 
 
CLN-PRO-V011 
 
 
 
 
 
 
Sponsor: 
 
 
Humacyte, Inc.  
Address: 
2525 East NC Highway 54 
Durham, NC 27713 
Phone:  
 
 
1.919.313.9633 
Fax: 
 
 
 
1.919.238.1719 
 
 
EudraCT No.:  
 
2018-003570-26 
 
Date:  
 
 
18 December 2018 
Version:  
 
 
1.2  
 
 
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 and 
ethical 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 Polish regulatory requirements 
 
 

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Site Principal Investigator Agreement Page for the Protocol 
Protocol Version 1.2 Dated: 18 December 2018 
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 Humacyte Incorporated (Humacyte) or their 
authorized representatives. 
• 
Not to implement any deviations from or changes to the protocol (including protocol 
amendments) without agreement from Humacyte and prior review and written approval 
from the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and 
Competent Authority, if applicable) except where necessary to eliminate an immediate 
hazard to the subject(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 Humacyte including, but 
not limited to the current Investigator Brochure or equivalent document. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the investigational medicinal product and about their study-related duties and functions. 
• 
That I have been informed that certain regulatory authorities require Humacyte to obtain 
and supply details about the investigator’s ownership interest in Humacyte or the 
Investigational Medicinal Product, and more generally about his/her financial ties with 
Humacyte. Humacyte will use and disclose the information solely for the purpose of 
complying with regulatory requirements. 
 
 
Principal Investigator:  _______________________________________________ 
Printed Name and Title 
 
Signed: 
 
Date: 
 

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Protocol Approval 
Sponsor Medical Approval:   
Jeffrey H. Lawson, MD, PhD 
Chief Executive Officer / Chief Medical Officer, Humacyte, Inc. 
Signed: 
Date: 
19Dec2018

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Table of Contents 
 
STATEMENT OF COMPLIANCE ................................................................................................................. 2 
SITE PRINCIPAL INVESTIGATOR AGREEMENT PAGE FOR THE PROTOCOL .................................... 3 
PROTOCOL APPROVAL ............................................................................................................................. 4 
LIST OF ABBREVIATIONS ........................................................................................................................ 10 
PROTOCOL SUMMARY ............................................................................................................................ 12 
1. 
STUDY PERSONNEL ......................................................................................................................... 18 
2. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ................................................... 19 
2.1 
END STAGE RENAL DISEASE AND ITS MANAGEMENT ....................................................................... 19 
2.1.1 Humacyte Human Acellular Vessel ......................................................................................... 20 
2.1.2 Scientific Rationale .................................................................................................................. 20 
2.2 
SUMMARY OF NONCLINICAL STUDIES .............................................................................................. 20 
2.3 
SUMMARY OF CLINICAL STUDIES .................................................................................................... 22 
2.3.1 Overview .................................................................................................................................. 22 
2.3.2 Experience in Dialysis Patients ............................................................................................... 23 
2.3.3 Experience in Peripheral Arterial Bypass Patients .................................................................. 24 
2.3.4 Human Acellular Vessel Host Response and Remodeling Data ............................................. 25 
2.3.5 Conclusions ............................................................................................................................. 27 
2.4 
STUDY DESIGN RATIONALE ............................................................................................................ 28 
2.5 
POTENTIAL RISKS AND BENEFITS ................................................................................................... 28 
2.5.1 Potential Risks ......................................................................................................................... 28 
2.5.2 Potential Benefits ..................................................................................................................... 29 
3. 
STUDY OBJECTIVES ........................................................................................................................ 30 
3.1 
PRIMARY OBJECTIVE ..................................................................................................................... 30 
3.2 
SECONDARY OBJECTIVE ................................................................................................................ 30 
4. 
STUDY DESIGN ................................................................................................................................. 31 
4.1 
DESCRIPTION OF THE STUDY DESIGN ............................................................................................. 31 
4.2 
STUDY ENDPOINTS ........................................................................................................................ 31 
4.2.1 Safety Endpoints ..................................................................................................................... 31 
4.2.2 Efficacy Endpoints ................................................................................................................... 32 

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4.3 
DURATION OF STUDY PARTICIPATION ............................................................................................. 32 
5. 
STUDY POPULATION ....................................................................................................................... 33 
5.1 
DESCRIPTION OF THE STUDY POPULATION ...................................................................................... 33 
5.1.1 Inclusion Criteria ...................................................................................................................... 33 
5.1.2 Exclusion Criteria ..................................................................................................................... 34 
6. 
INVESTIGATIONAL MEDICINAL PRODUCT ................................................................................... 36 
6.1 
HUMAN ACELLULAR VESSEL ........................................................................................................... 36 
6.1.1 Product Description ................................................................................................................. 36 
6.1.2 Manufacturer of the Investigational Medicinal Product ........................................................... 36 
6.1.3 Packaging, Storage, and Labeling .......................................................................................... 37 
6.1.4 Implantation of the Humacyte Human Acellular Vessel .......................................................... 37 
6.2 
INVESTIGATIONAL MEDICINAL PRODUCT ACCOUNTABILITY PROCEDURES ......................................... 38 
6.2.1 Human Acellular Vessel .......................................................................................................... 38 
7. 
OTHER TREATMENTS AND MEDICATIONS ................................................................................... 39 
7.1 
PRIOR AND CONCOMITANT MEDICATIONS ....................................................................................... 39 
7.2 
ESSENTIAL AND RESTRICTED MEDICATIONS .................................................................................... 39 
7.2.1 Essential Medications .............................................................................................................. 39 
7.2.2 Restricted Medications ............................................................................................................ 40 
8. 
STUDY PROCEDURES/EVALUATIONS ........................................................................................... 41 
8.1 
SCREENING (BASELINE) (DAY -45 TO DAY 0) .................................................................................. 41 
8.1.1 Informed Consent .................................................................................................................... 41 
8.1.2 Demographics.......................................................................................................................... 41 
8.1.3 Medical History ........................................................................................................................ 41 
8.1.4 Prior and Concomitant Medications ........................................................................................ 42 
8.1.5 Physical Exam, Vital Signs and Temperature ......................................................................... 42 
8.1.6 Electrocardiogram ................................................................................................................... 42 
8.1.7 Laboratory Evaluations ............................................................................................................ 42 
8.1.8 Vessel Mapping ....................................................................................................................... 43 
8.1.9 Assessment of Central Vein Stenosis ..................................................................................... 43 
8.1.10 Review of Subject Eligibility ..................................................................................................... 43 
8.1.11 Serious Adverse Events .......................................................................................................... 43 

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8.2 
SURGICAL PLACEMENT OF THE HAV (DAY 0) .................................................................................. 43 
8.2.1 Medical History and Concomitant Medications ....................................................................... 43 
8.2.2 Symptom-directed Physical Examination, including Temperature .......................................... 43 
8.2.3 Confirmation of Subject Eligibility ............................................................................................ 44 
8.2.4 Surgical Placement .................................................................................................................. 44 
8.2.5 Confirmation of Patency .......................................................................................................... 44 
8.2.6 Adverse Events ....................................................................................................................... 44 
8.3 
POSTOPERATIVE EVALUATION-DAY 7-15 VISIT ................................................................................ 44 
8.3.1 Concomitant Medications ........................................................................................................ 44 
8.3.2 Symptom-directed Physical Examination, including Temperature .......................................... 44 
8.3.3 Assessment of Surgical Site Healing ...................................................................................... 45 
8.3.4 Assessment of Problems with the Access Site or HAV and HAV Interventions ..................... 45 
8.3.5 Assessment of HAV Patency and Flow ................................................................................... 45 
8.3.6 Assessment of Hemodialysis and Placement and/or Removal of Central Venous Catheter .. 45 
8.3.7 Assessment of Adverse Events ............................................................................................... 45 
8.3.8 Assessment of Events of Special Interest ............................................................................... 45 
8.4 
POSTOPERATIVE EVALUATION-DAY 28 (± 7D) VISIT ........................................................................ 46 
8.4.1 Concomitant Medications ........................................................................................................ 46 
8.4.2 Symptom-directed Physical Examination, including Temperature .......................................... 46 
8.4.3 Assessment of Surgical Site Healing ...................................................................................... 46 
8.4.4 Clinical Examination of the Access Site and HAV ................................................................... 46 
8.4.5 Assessment of any Problems with Access Site or HAV and HAV Interventions ..................... 47 
8.4.6 Assessment of HAV Patency ................................................................................................... 47 
8.4.7 Duplex Ultrasound ................................................................................................................... 47 
8.4.8 Determination that the HAV may be used for Dialysis ............................................................ 47 
8.4.9 Assessment of Hemodialysis and Placement and/or Removal of Central Venous Catheter .. 47 
8.4.10 Assessment of Adverse Events ............................................................................................... 48 
8.4.11 Assessment of Events of Special Interest ............................................................................... 48 
8.4.12 Laboratory Evaluations ............................................................................................................ 48 
8.5 
POSTOPERATIVE EVALUATIONS (MONTH 2 TO MONTH 12) ............................................................... 48 
8.5.1 Evaluations and Procedures to be performed at All Study Visits from Month 2 to Month 12 . 48 

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8.5.2 Evaluations and Procedures to be performed only at Specific Visits from Month 2 to Month 12
 50 
8.6 
LONG TERM FOLLOW UP POST MONTH 12 THROUGH MONTH 36 EVALUATIONS AND PROCEDURES ... 50 
8.6.1 Evaluations and Procedures that will be performed at All Study Visits Post Month 12 to Month 
36 (± 1M) ................................................................................................................................. 50 
8.7 
EARLY TERMINATION VISIT ............................................................................................................. 52 
8.7.1 Concomitant Medications (if prior to month 12) ....................................................................... 52 
8.7.2 Symptom-directed Physical Examination, including Temperature .......................................... 52 
8.7.3 Clinical Examination of the Access Site and HAV ................................................................... 52 
8.7.4 Assessment of HAV Patency ................................................................................................... 52 
8.7.5 Assessment of any Problems with the Access Site or HAV and Interventions, Including 
Events of Special Interest ........................................................................................................ 52 
8.7.6 Duplex Ultrasound ................................................................................................................... 53 
8.7.7 Assessment of Hemodialysis and Placement and/or Removal of Central Venous Catheter .. 53 
8.7.8 Assessment of Adverse Events ............................................................................................... 53 
8.7.9 PRA and Anti-HAV IgG Antibodies (if prior to month 12) ........................................................ 53 
8.8 
COLLECTION AND PROCESSING OF LABORATORY SAMPLES ............................................................. 53 
9. 
SAFETY ASSESSMENTS AND ADVERSE EVENTS ....................................................................... 54 
9.1 
DEFINITION OF ADVERSE EVENTS ................................................................................................... 54 
9.2 
DEFINITION OF SERIOUS ADVERSE EVENTS .................................................................................... 54 
9.2.1 Suspected Unexpected Serious Adverse Reactions ............................................................... 55 
9.3 
EVENTS OF SPECIAL INTEREST ....................................................................................................... 55 
9.4 
CRITERIA FOR DETERMINING CAUSAL RELATIONSHIP TO THE HAV AND CRITERIA FOR DETERMINING 
CASUAL RELATIONSHIP TO INDEX SURGICAL PROCEDURE ............................................................... 57 
9.5 
CRITERIA FOR DEFINING THE SEVERITY OF AN ADVERSE EVENT ...................................................... 58 
9.6 
REPORTING OF ADVERSE EVENTS .................................................................................................. 58 
9.6.1 Reporting of Serious Adverse Events ..................................................................................... 59 
9.6.2 Monitoring and Reporting of Serious Adverse Events Not Related to the HAV ...................... 60 
9.6.3 Follow-Up of Adverse Events .................................................................................................. 60 
9.7 
REPORTING OF PREGNANCY .......................................................................................................... 60 
9.8 
STUDY SUSPENSION AND STOPPING CRITERIA ................................................................................ 61 
9.9 
DATA MONITORING COMMITTEE ..................................................................................................... 61 

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9.10 
NEW INFORMATION AFFECTING THE CONDUCT OF THE STUDY ......................................................... 61 
10. STATISTICAL CONSIDERATIONS ................................................................................................... 61 
11. STUDY MANAGMENT AND DATA COLLECTION ........................................................................... 62 
11.1 
ETHICAL CONDUCT OF THE TRIAL ................................................................................................... 62 
11.2 
SUBJECT CONFIDENTIALITY ............................................................................................................ 62 
11.3 
INDEPENDENT ETHICS COMMITTEE ................................................................................................. 62 
11.4 
SUBJECT INFORMED CONSENT ....................................................................................................... 63 
11.5 
SUBSTANTIAL AMENDMENTS TO THE PROTOCOL ............................................................................. 64 
11.6 
STUDY INITIATION .......................................................................................................................... 64 
11.7 
STUDY MONITORING ...................................................................................................................... 64 
11.8 
CASE REPORT FORM ..................................................................................................................... 65 
11.8.1 Data Management ................................................................................................................... 65 
11.9 
VERIFICATION PROCEDURES .......................................................................................................... 65 
11.10 RETENTION OF RECORDS ............................................................................................................... 65 
11.11 PROTOCOL DEVIATIONS ................................................................................................................. 66 
11.12 INSURANCE AND INDEMNITY ........................................................................................................... 66 
11.13 AUDIT ........................................................................................................................................... 66 
12. REPORTING ....................................................................................................................................... 68 
12.1 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................................ 68 
13. RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR ............................................................ 69 
13.1 
INFORMED CONSENT ..................................................................................................................... 69 
13.2 
COMPLIANCE WITH THE PROTOCOL ................................................................................................ 69 
13.3 
MEDICAL CARE OF SUBJECTS ........................................................................................................ 70 
13.4 
SAFETY REPORTING ...................................................................................................................... 71 
14. SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL INVESTIGATION ............... 72 
15. PUBLICATION POLICY ..................................................................................................................... 73 
16. REFERENCES .................................................................................................................................... 74 
APPENDIX 1:  VISIT SCHEDULE .............................................................................................................. 76 
 
List of In-text Figures 
Figure 1  
Images of Mid-Vessel Segment Explanted at 11-Months Post-Implant .................... 27 
 

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List of Abbreviations  
 
 
AE 
Adverse event 
AV 
Arteriovenous 
AVF 
Autologous arteriovenous fistula 
BUN 
Blood urea nitrogen 
CDC 
Center for Disease Control and Prevention 
CEC 
Clinical Events Committee 
CKD 
Chronic kidney disease 
CRO 
Contract research organization 
CSR 
Clinical Study Report 
CVC 
Central venous catheter 
D 
Day 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
ECM 
Extracellular Matrix 
eCRF 
Electronic case report form 
ePTFE 
Expanded polytetrafluoroethylene 
ESRD 
End-stage renal disease 
ET 
Early termination 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HAV 
Human acellular vessel (note was HAVG [Human Acellular Vascular 
Graft]) 
HbA1c 
Hemoglobin A1c 
ICH 
International Conference on Harmonization  
IEC 
Independent ethics committee 
IgG 
Immunoglobulin G 
IMP 
Investigational medicinal product 
IND 
Investigational new drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
K-M 
Kaplan Meier 
LMWH 
Low molecular weight heparin 

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List of Abbreviations  
M 
Month 
PAD 
Peripheral arterial disease 
PE 
Physical examination 
PRA 
Panel reactive antibody 
PT 
Prothrombin time 
PTFE 
Polytetrafluoroethylene 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
spKt/Vurea 
Measure of dialysis adequacy for a single hemodialysis treatment 
using the single pooled method 
SUSAR 
Suspected unexpected serious adverse reaction 
US 
United States  
WBC 
White blood cell 
 
 

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Protocol Summary 
Full Title 
A Phase 2 Assessment of Humacyte’s Human Acellular Vessel in 
Patients Needing Vascular Access for Dialysis 
Clinical Trial Phase 
Phase 2 
Sponsor  
Humacyte, Inc. 
Planned Study Sites 
2 sites in Poland 
Sample Size 
Up to 30 patients implanted with a Human Acellular Vessel (HAV) 
Expected Enrollment 
Start 
2Q 2019 
Study Rationale 
Previous studies with the HAV have used Investigational Medicinal 
Product (IMP) manufactured using small-scale systems (Aura and 
Terra). Prior to commercialisation, manufacturing has been switched 
to a larger-scale automated process with greater in-process controls 
(Luna). Based on a large number of preclinical parameters, 
including those used for batch release, the IMP manufactured using 
the Luna system is comparable to that used in earlier clinical 
studies. This study will allow confirmation of the short-term safety, 
efficacy and absence of immunogenicity of the Luna product.   
Study Population 
Subjects with end-stage renal disease (ESRD) who require 
hemodialysis and are targeted for implantation of an arteriovenous 
(AV) graft for dialysis access. 
Enrollment Period 
2 months 
Study Duration 
Each subject will be followed by study specific visits until he/she 
completes 1 year (12 months) of follow-up after implantation 
(irrespective of patency status). After 1 year, only subjects with a 
patent HAV will be followed (while the HAV remains patent) for up to 
3 years (36 months) post-implantation at study visits every 
6 months. The expected duration of the clinical investigation is 
41 months (initiation of enrollment through completion of data 
collection). 
Study Design 
Prospective, two center, open-label, single-arm study. 
Intervention 
Description 
The IMP is Humacyte’s HAV, which is a tissue-engineered vascular 
conduit for hemodialysis access. HAVs for this study will be 
manufactured using the Luna commercial manufacturing system. 
Subjects will be implanted with an HAV in the forearm or upper arm 

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using standard vascular surgical techniques.  
All subjects will be required to take daily aspirin (75 to 325 mg) 
unless they are already taking another antiplatelet agent. Aspirin 
should be initiated no later than the day after surgical implantation of 
the HAV (Day 1). If low molecular weight heparin (LMWH) is 
administered post-operatively, aspirin or other antiplatelet agents 
should be initiated after stopping LMWH. 
Subjects who are known to be aspirin-sensitive should take another 
antiplatelet agent at the discretion of the Principal Investigator. 
Objectives 
 
Primary Objective 
To evaluate the safety, efficacy and immunogenicity over 3 months 
after implantation of HAVs manufactured using the commercial 
manufacturing system (Luna) 
Secondary Objectives 
To evaluate the long-term safety and efficacy of the HAV 
(manufactured with the Luna system) over a period of up to 
36 months after implantation 
Inclusion Criteria 
1. Subjects with ESRD who are not, or who are no longer, 
candidates for creation of an autologous AV fistula (AVF) and 
who need placement of an AV graft in the arm (upper- or 
forearm) for hemodialysis therapy. 
2. Already established on hemodialysis.  
3. At least 18 years of age at Screening. 
4. Suitable arterial and venous anatomy for implantation of 
straight or looped conduits in either the forearm or upper arm 
(not crossing the elbow). 
5. Hemoglobin ≥ 8 g/dL and platelet count ≥ 100,000 cells/mm3 
prior to Day 0 (within 45 days). 
6. Other hematological and biochemical parameters within a 
range consistent with ESRD prior to Day 0 (within 45 days). 
7. Normal clotting (international normalized ratio [INR] ≤ 1.5 or 
prothrombin time ≤ 18 sec unless the patient is taking an 
anticoagulant for an approved indication at the time of HAV 
implantation. 
8. Female subjects must be either: 
a. Of non-childbearing potential, which is defined as 
post-menopausal (at least 1 year without menses 

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prior to Screening) or documented surgically sterile or 
post hysterectomy (at least 1 month prior to 
Screening) 
b. Or, of childbearing potential, in which case: 
i. Must have a negative serum or urine 
pregnancy test at Screening, and 
ii. Must agree to use at least one form of the 
following birth control methods for the duration 
of the study: 
1. Established use of oral, injectable or 
implanted 
hormonal 
methods 
of 
contraception 
2. Placement of an intrauterine device or 
intrauterine system 
3. Barrier 
methods 
of 
contraception: 
condom or occlusive cap (diaphragm 
or cervical/vault caps) with spermicidal 
foam/gel/film/cream/suppository 
9. Subject, or legal representative, able to communicate 
effectively with investigative staff, competent and willing to 
give written informed consent, and able to comply with entire 
study procedures including all scheduled follow-up visits. 
10. Life expectancy of at least 1 year. 
Exclusion Criteria 
1. History or evidence of severe peripheral vascular disease in the 
intended arm for implantation. 
2. Known or suspected central vein stenosis or conduit occlusion 
on the ipsilateral side of the planned implantation, unless the 
stenosis is corrected prior to HAV implantation. 
3. Treatment with any investigational drug or device within 60 days 
prior to study entry (Day 0) or ongoing participation in a clinical 
trial of an investigational product. 
4. Cancer that is actively being treated with a cytotoxic agent. 
5. Documented hyper-coagulable 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 

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events (e.g. deep vein thrombosis, pulmonary 
embolism, etc.) within the 5 previous years. 
6. Spontaneous or unexplained bleeding diathesis clinically 
documented within the last 5 years or a biochemical diagnosis 
(e.g. von Willebrand disease, etc.). 
7. Active clinically significant immune-mediated disease, not 
controlled by maintenance immunosuppression (low dose 
steroid therapy only) 
a. Low dose glucocorticoid therapy (e.g. up to 10 mg a 
day prednisone or prednisolone) is acceptable. 
b. High dose glucocorticoid therapy for treatment of 
autoimmune flare, or other inflammatory diseases is 
excluded. 
c. Patients 
using 
glucocorticoids 
for 
immunosuppression 
post-transplant 
to 
prevent 
against transplanted allograft rejection in the period 
post allograft failure are excluded. 
d. The following examples of immunosuppressive 
agents (or the like) are exclusionary for enrollment in 
this clinical trial: 
i. tacrolimus or FK506 [Prograf] 
ii. mycophenolate mofetil [Cellcept],  
iii. cyclosporine [Sandimmune or Gengraf] 
iv. Sirolimus administered systemically (Sirolimus 
in drug eluting stents is NOT an exclusion) 
8. Anticipated renal transplant within 6 months. 
9. Venous outflow from HAV cannot be placed more centrally than 
the venous outflow of any previous failed access in that 
extremity. 
10. Active 
local 
or 
systemic 
infection 
(white 
blood 
cells 
[WBC] > 15,000 cells/mm3 
at 
Screening). 
If 
the 
infection 
resolves, the subject must be at least 1 week post resolution of 
that infection before implantation. 
11. Known serious allergy to planned antiplatelet agent. 
12. Pregnant women, or women intending to become pregnant 
during the course of the trial. 
13. Any other condition which in the judgment of the investigator 

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would preclude adequate evaluation of the safety and efficacy of 
the HAV. 
14. Previous enrollment in this study or any other study with the 
HAV. 
15. Employees of Humacyte and employees or relatives of the 
investigator. 
Criteria for Evaluation 
 
Primary Endpoints – 
assessed at 3 months 
post implantation 
 
Safety  
• 
Adverse events indicating possible mechanical failure or 
weakness of the HAV (anastomotic rupture, anastomotic 
bleeding, 
spontaneous 
HAV 
rupture, 
aneurysm, 
pseudoaneurysm, abnormal post cannulation hemostasis) 
• 
HAV infections 
• 
Change from baseline of panel reactive antibody (PRA) and 
anti-HAV IgG levels (at 2 months) 
• 
All adverse events (AEs)/serious adverse events (SAEs) and 
adverse events of special interest. 
Efficacy 
• 
Primary / primary assisted/secondary patency 
Secondary Endpoints – 
assessed throughout the 
36 month follow up  
Safety 
• 
Adverse events indicating possible mechanical failure or 
weakness of the HAV (anastomotic rupture, anastomotic 
bleeding, 
spontaneous 
HAV 
rupture, 
aneurysm, 
pseudoaneurysm, abnormal post cannulation hemostasis) 
• 
HAV infections  
• 
Change from baseline of PRA and anti-HAV IgG values (at 
12 months) 
• 
All AEs/SAEs until 12 months post implant, after that only 
SAEs related to the HAV and adverse events of special 
interest 
 
Efficacy 
• 
Primary/primary assisted/secondary patency 
• 
Interventions 
required 
to 
achieve/maintain 
secondary 
patency. 
• 
Histopathological remodeling of any HAV (based on any 

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samples collected). 
 
Data Analysis 
This is an exploratory study with no formal hypothesis testing. Data 
will be summarized using descriptive statistics only.  
All available data will be summarized and reported in a clinical study 
report (CSR) when the last patient completes 3 months of follow up. 
A second analysis will be conducted when all patients have 
completed 12 months of follow up. The final analysis will occur when 
the final patient completes 36 months of follow up. 
Study Oversight 
Data Monitoring 
Committee (DMC) 
An independent Data Monitoring Committee (DMC) has been 
established to review safety on an ongoing basis across the entire 
clinical program and to provide recommendations about stopping, 
continuing or otherwise modifying studies. Responsibilities of the 
DMC will include review of safety data from this study. DMC will 
review data from this study on an ongoing basis with the 1st 
scheduled DMC review after the last patient completes Month 3 and 
every 6 months thereafter. 
The DMC consists of individuals who are not directly involved in the 
conduct of the study. A separate charter has been established that 
describes the roles and responsibilities of the DMC.  
Protocol Approval 
(Version and Date) 
v1.2    18 December 2018 
 
 

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1. STUDY PERSONNEL 
A list of all study personnel will be maintained by the Contract Research Organization (CRO). 
Substantial protocol amendments will not be required for staff changes at Humacyte or the 
CRO. 
 
Humacyte Medical Representative 
Jeffrey H. Lawson, MD, PhD 
Chief Executive Officer and Chief Medical Officer 
Humacyte, Inc. 
2525 East NC Highway 54 
Durham, NC 27713, US  
E-mail:  
 
lawson@humacyte.com 
Phone:  
 
1.919.630.7851 
 
Humacyte Clinical Operations Representative 
Angela Rose 
Sr. Director, Clinical Development 
Humacyte, Inc. 
2525 East NC Highway 54 
Durham, NC 27713, USA 
E-mail:  
 
rose@humacyte.com 
Mobile Phone:  
1.919.667.3507 
 
Humacyte Regulatory Representative 
William Tente, MS 
Chief Regulatory Officer 
Humacyte, Inc.  
2525 East NC Highway 54 
Durham, NC 27713, USA 
E-mail:  
 
tente@humacyte.com 
Office Phone:  
1.919.313.9633  
Mobile Phone:  
1.401.714.4151 
 
 

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2. BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 End Stage Renal Disease and its Management 
Chronic kidney disease (CKD) is a serious and growing worldwide health problem. At the end of 
2012, there were 26 million American adults with CKD, of these ~600,000 had End Stage Renal 
Disease (ESRD) and ~400,000 were receiving hemodialysis (National Kidney Foundation 
2014). In Europe, there are approximately 780,000 patients on dialysis, with an expectation that 
this population will grow (ERA-EDTA Registry 2014). As patients with CKD progress to ESRD 
there is a need to consider renal replacement therapy. The first choice is usually a renal 
transplant, but this is not always available and many patients need to start dialysis – either 
peritoneal dialysis or hemodialysis. 
Vascular access is a prerequisite for hemodialysis. It allows blood to be directed to an 
extracorporeal dialysis machine and returned to the patient. The commonly accepted standards 
for dialysis management urge providers to consider an autologous arteriovenous fistula (AVF) 
as the first line strategy for permanent hemodialysis access (National Kidney Foundation 2006). 
Unfortunately, not all patients are candidates for native fistulae and many require synthetic 
grafts for vascular access. In these cases synthetic vascular grafts are used; currently available 
synthetic grafts are typically made of materials such as polytetrafluoroethylene (PTFE).   
However, synthetic grafts are subject to complications, often frequent, that limit their long-term 
utility. Typical complications include infections, which may necessitate their removal (Nassar 
2001, Ryan 2004), and thrombosis, with or without stenosis associated with intimal hyperplasia, 
that necessitate interventions to remove the thrombus, with or without angioplasty to open 
associated stenosis (Haskal 2010, Roy-Chaudhury 2001). While highly variable, the published 
literature suggests that synthetic grafts may have a primary patency of ~60% after 6 months 
and even less later, with secondary patency of ~60% after 1 year (Dixon 2009, Huber 2003, 
Miller 2007).  
Multiple biological alternatives to synthetic grafts have been studied for dialysis access, but 
results have been generally poor with a high risk of aneurysmal dilatation. Retained xenogeneic 
cellular remnants also have the potential for an induced immune response to implanted 
materials (Smith 2009).   
If neither synthetic grafts nor biological alternatives are available, many patients are forced to 
rely on long-term central vein catheters (CVC) for vascular access; however, CVCs are 
associated with a high potential for infection and shorter patient survival (Bray 2012, Thompson 
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There is, thus, a need for alternative conduits that more closely mimic human vascular tissue 
and thus might avoid, or reduce, complications while providing a more durable vascular access. 
2.1.1 Humacyte Human Acellular Vessel 
The investigational medicinal product (IMP) is Humacyte’s Human Acellular Vessel (HAV), 
which is a tissue-engineered vascular conduit developed to provide an alternative to synthetic 
and autologous conduits for vascular access for dialysis.  
The HAV is cultured from human aortic vascular smooth muscle cells, in a bioreactor that 
imparts arterial-like strain conditions on the growing cells. After an 8-week culture period, the 
tissue is decellularized, to produce the final HAV. It is a sterile, non-pyrogenic acellular tubular 
vessel composed, primarily, of human collagen types I and III plus other extracellular matrix 
(ECM) proteins, including fibronectin and vitronectin. The HAV is 6 mm in diameter and 
approximately 42 cm in length.  
2.1.2 Scientific Rationale 
Previous studies with the HAV have used IMP manufactured using small-scale systems (Aura 
and Terra). Prior to commercialisation manufacturing has been switched to a larger-scale 
automated process with greater in-process controls (Luna). Based on a large number of 
preclinical parameters, including those used for batch release, the IMP manufactured using the 
Luna system is comparable to that used in earlier clinical studies. This study will allow 
confirmation of the short-term safety, efficacy and absence of immunogenicity of the Luna 
product.   
2.2 Summary of Nonclinical Studies 
Humacyte conducted 13 nonclinical studies to evaluate the safety and functionality of the HAV. 
These studies assessed the HAV prototypes, the HAV and extracts of the ECM material.  
A xenograft-primate model (immunosuppressive-free) was developed to assess the 
performance of the HAV implanted as an arterio-venous shunt. Two pilot studies and 2 definitive 
Good Laboratory Practice (GLP)-compliant studies were performed in baboons (n = 14) to 
investigate the safety and functionality of the HAV. The first 2 animals had the HAV implanted in 
the abdomen; in the remaining 12 animals the HAVs were implanted in the upper arm. Shared 
objectives across these studies encompassed an assessment of potential local and systemic 
responses, patency, tolerability, physical and biological properties of the HAV or HAV-derived 
material and integration of the graft material with the host tissue after implantation periods of 
1-6 months. In addition, immunological studies were conducted to assess humoral and cellular 
immune reactions associated with the HAV. 
Overall, the results showed that the HAV was safe and well tolerated. For the 12 baboons with 
the HAV implanted in the upper arm, with the exception of post-operative arm swelling and 

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redness, as well as surgical incision perturbation by a few animals, no significant issues 
associated with implantation of the HAV were encountered. In addition, these animals 
maintained their body weight and showed no outward signs indicative of toxicity. Clinical 
chemistry and hematological findings showed no evidence of systemic toxicity. Liver, pancreas, 
and kidney function tests remained within normal ranges. Gross observations of the major and 
minor organs at necropsy indicated that, in general, there were no notable abnormalities or 
changes attributable to the test article, including the heart, spleen, liver, kidney, brain, and lung. 
In 4 animals, swollen and/or inflamed lymph nodes were observed. Histopathologic examination 
of the heart, liver, kidney, brain, and lung revealed no significant abnormalities. In cases where 
microscopic findings were observed, they were considered to be unrelated to the test article. 
In general, the HAV functioned as intended. Assessments of performance included HAV 
puncture, angiography and ultrasound. Ultrasonography showed no wall thickening of the HAV 
during the study. Flow rates through the HAV were determined to be > 300 mL/min, adequate 
for hemodialysis in humans. The overall assisted patency rate was approximately 80% 
(11/14 animals). The degree and aggressiveness of the intimal hyperplasia response, a major 
cause of failure for PTFE arteriovenous (AV) grafts, was insignificant. The HAV were accessed 
successfully with 16-22 gauge needles followed by a 5 French sheathed access catheter. 
Hemostasis was achieved with light pressure, typically in under 10 minutes. In the majority of 
animals, macroscopic examination of the HAV and associated vasculature at explant indicated 
that they were intact and were not dilated, constricted, calcified or aneurysmal. Enlargement of 
the outflow brachial vein, a typical response associated with the increased blood flow into the 
vein, was common. Scarring was not observed. Host tissue growth that resembled adventitia 
was evident around the exterior of the HAV. The HAV were measured for strength pre-implant 
and post-explant by a suture retention test. The HAV generally had increased suture retention 
values post-explant, most likely due to the host remodeling the graft with cells and native ECM. 
No evidence of systemic infection attributable to implantation of the HAV was observed in any of 
the animals. One HAV developed an aneurysm that was resected and did not harm the animal.  
Microscopic analysis indicated that the HAV integrated with the host tissue. The cellular host 
response to the HAV demonstrated smooth muscle actin-positive cells within the vessel wall, 
endothelial cells lining the lumen, and an adventitial-like outer layer adjacent to the HAV similar 
to that of native blood vessels. Calcification was not observed. The HAV were therefore 
populated with cell types characteristic of healthy native vasculature. Immunostaining showed 
that collagen type I, collagen type III, and fibronectin within the vessel wall displayed a more 
organized structure with more circumferential alignment after 6 months. Additionally, collagen 
type I, glycosaminoglycans, and elastin deposition increased over this time period. The 
observed changes in organization and composition of ECM components indicated that, aided by 
infiltration of host vascular cells, HAV were re-modeled in vivo in a manner that mimicked the 
dynamic re-modeling process of native blood vessels. 
The HAV did not elicit biologically-significant humoral or cellular immune response. Analysis of 
panel reactive antibody (PRA) levels showed no increase for any animal, indicative that the HAV 
did not cause production of the anti-human antibodies measured by this assay. In an in vitro 

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T-cell proliferation assay, low stimulation rates (3% to 17%; at or below that of negative control) 
were observed when buffy coat cells from each animal were cultured with HAV material. 
Increases in immunoglobulin G (IgG) titer to the ECM, defined as > 25 fold titer increase over 
baseline, were observed in all study animals regardless of HAV functional outcome. In addition 
to the implant of the HAV test article, an additional test article consisting of a micronized extract 
of the HAV, as well as phosphate-buffered saline (negative control), were injected intra-dermally 
into the upper hip/thigh of all animals to monitor for the development of a delayed-type 
hypersensitivity immune response. No delayed-type hypersensitivity reactions were observed in 
any animals.  
Biocompatibility assessments of the HAV ECM were conducted in accordance with 
internationally-recognized (International Organization for Standardization) protocols for medical 
implants. The ECM was tested in vivo in rabbits (1 and 4-weeks, intramuscular implantation) 
and in vitro in a bacterial reverse mutation assay (Ames) and a cytotoxicity assay using mouse 
fibroblast cells. The ECM met all toxicological and biocompatibility requirements in the in vivo 
rabbit model and also tested negative for mutagenic and cytotoxic activity in the in vitro tests. 
Further details on the nonclinical development program are presented in the Investigator 
Brochure. 
2.3 Summary of Clinical Studies 
2.3.1 Overview 
The HAV clinical development program currently includes 7 clinical studies: 4 in patients with 
end-stage 
renal 
disease 
receiving 
hemodialysis 
(CLN-PRO-V001, 
CLN-PRO-V003, 
CLN-PRO-V006 and CLN-PRO-V007), 2 in patients with peripheral arterial disease 
(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, CLN-PRO-V005) and 1 phase 3 study (CLN-PRO-V007) are open for 
enrollment.  
As of 10 April 2018, 272 patients (244 hemodialysis access patients and 28 peripheral arterial 
disease [PAD] 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 329 patient years in the hemodialysis access population 
and 55 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. 

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2.3.2 Experience in Dialysis Patients 
Two Phase 2 trials, 1 in Poland (CLN-PRO-V001) and 1 in the United States (US) 
(CLN-PRO-V003) have completed enrollment. Both recruited subjects requiring hemodialysis 
access for end-stage renal disease whom were not suitable for creation of an 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 2 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 extracellular matrix 
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. A second phase 
3 randomized study (CLN-PRO-V007) comparing HAV with AVF is currently enrolling in the US. 
As the sponsor is blinded, no efficacy information currently available for the phase 3 studies; 
however, blinded safety data is presented in the Investigator Brochure. 
2.3.2.1 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 2 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 graft aneurysm was reported in Study CLN-PRO-V001 
(moderate in intensity, considered possibly related to 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 1 or more renal transplant failures; 1 subject recently; 1 subject 
developed septic shock about a month before the elevated value; and the third subject, who 

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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 1 case 
the IgG titer increase occurred in a subject who maintained primary patency.  
Adverse events (AEs) related to the HAV/access site (excluding thrombotic events) were few; 
there have been only 3 access-site infections, of which only 1 required removal of part of the 
HAV. There have been:  
• 
1 kidney 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 2 studies in dialysis access has been pooled for a combined Kaplan-Meier 
(K-M) analysis (Lawson, 2016). Based on these K-M plots the patency at 6, 12 and 24 months is 
estimated to be 60%, 26% and 15% (primary patency) and 97%, 91% and 77% (secondary 
patency). 
2.3.3 Experience in Peripheral Arterial Bypass Patients 
Humacyte has 2 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 peripheral 
arterial disease. Pre-operative imaging (conventional or computed tomography [CT] 
angiography) must have demonstrated at least 2 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 (conventional or intra-op CT angiography) or 
ultrasound. The patient was then followed up 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, 
and the HAV was examined using duplex ultrasound 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 PRA and IgG response to the HAV and to 

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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 with 
enrollment ongoing. 
2.3.3.1 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 7 patients terminating 
the study early, 3 died and 4 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.  
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. 
2.3.4 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 in 8 cases. The analysis 
(mostly of a section close to the venous anastomosis) included assessments of:  

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• 
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 these 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 
55 weeks (median: 37 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, 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 1 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. 
 

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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 images above show a mid-vessel segment explanted at 11 months post-implant, and shows several prior cannulation tracts 
from dialysis access. Section B shows a very recent cannulation site with fresh clot extending into the tract from the lumen.  
Sections C and D show partially healed 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. 
2.3.5 Conclusions 
Clinical experience indicates that the HAV remains mechanically strong over implantation 
periods of more than 60 months with no evidence of dilatation. During more than 200 patient 
years of follow up across the 3 Phase 2 studies only 1 case of infection of the HAV material 

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itself has been reported. 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. 
2.4 Study Design Rationale 
Previous studies with the HAV have used IMP manufactured using small-scale systems (Aura 
and Terra). Prior to commercialisation, manufacturing has been switched to a larger-scale 
automated process with greater in-process controls (Luna). Based on a large number of 
preclinical parameters, including those used for batch release, the IMP manufactured using the 
Luna system is comparable to that used in earlier clinical studies. This study will allow 
confirmation of the short-term safety, efficacy and absence of immunogenicity of the Luna 
product. 
Any significant safety or immunogenicity concerns with the HAV would likely be apparent in a 
short time frame after implant. Thus, the initial study analysis will be conducted after all subjects 
have reached 3 months post-implant. However, all subjects will be followed for 12 months and 
those with a patent HAV will continue follow up to 36 months to monitor for any potential long-
term safety concerns with the Luna product. 
2.5 Potential Risks and Benefits 
2.5.1 Potential Risks 
It is anticipated that subjects participating in the study will be exposed to the same risks as 
those associated with AV graft implantation (some of which have been reported in Phase 2 trial 
with the HAV – see Investigator Brochure). Risks associated with the HAV may include, but are 
not limited to, the following: 
• 
Aneurysm or pseudo-aneurysm formation 
• 
HAV rupture 
• 
Bleeding and hematoma formation at the surgical site or the dialysis puncture sites 
• 
Thrombosis/occlusion of the HAV or host vessels 

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• 
Stenosis of the HAV or its anastomoses 
• 
Infection of the HAV, at the surgical site or a systemic infection 
 
• 
Skin erosion 
• 
Steal syndrome and/or high output cardiac failure 
• 
Swelling of the limb 
The risks anticipated in this study are similar to those associated with currently marketed 
prosthetic grafts used for dialysis access. There has been 1 reported aneurysmal dilatation of 
the HAV in Phase 2. The superficial site of implantation of the HAV facilitates clinical and 
regular ultrasound monitoring, allowing any such complication to be recognized and treated 
promptly, and thus minimizing potential risk to the subject. 
The HAV is grown using donor human aortic smooth muscle cells. The HAV is decellularized 
during manufacturing and thus consists of only human ECM proteins. It is possible that the HAV 
may provoke an immune response which may lead to damage of the HAV and possible cross 
reactivity against host proteins. Antibody formation will be assessed by monitoring of PRA 
levels. 
2.5.2 Potential Benefits 
Subjects who undergo implantation of the Humacyte HAV may benefit from reduced infections 
and improved patency, which may translate into a reduced number of interventions versus a 
conventional ePTFE graft. Based on the known biology of the HAV, the HAV has the potential to 
offer a reduced risk of infection and less intimal hyperplasia, which could offer a longer period of 
use (i.e., delayed abandonment). 
 

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3. STUDY OBJECTIVES 
3.1 Primary Objective 
To evaluate the safety, efficacy and immunogenicity over 3 months after implantation of HAVs 
manufactured using the commercial manufacturing system (Luna). 
3.2 Secondary Objective 
To evaluate the long-term safety and efficacy of the HAV (manufactured with the Luna system) 
over a period of up to 36 months after implantation. 
 

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4. STUDY DESIGN 
4.1 Description of the Study Design 
This is a Phase 2, prospective, multicenter, open-label, single-arm study. Subjects who sign 
informed consent would undergo study-specific screening assessments within 45 days from the 
day of informed consent.  
Eligible study subjects will receive a HAV and will be followed to 12 months post-implantation at 
routine study visits regardless of patency status. After 12 months, subjects with a patent HAV 
will be followed (while the HAV remains patent) for up to 3 years (36 months) post-implantation 
at study visits every 6 months. 
4.2 Study Endpoints 
4.2.1 Safety Endpoints 
4.2.1.1 Primary Safety Endpoints – assessed at 3 months post implantation 
• 
Adverse events indicating possible mechanical failure or weakness of the HAV  
o Anastomotic rupture 
o Anastomotic bleeding  
o Spontaneous HAV rupture  
o Aneurysm  
o Pseudoaneurysm  
o Abnormal post cannulation hemostasis 
• 
HAV infections 
• 
Change from baseline of PRA and anti-HAV IgG levels (at 2 months) 
• 
All AEs/SAEs and adverse events of special interest. 
4.2.1.2 Secondary Safety Endpoints – assessed throughout the 36 month post 
implantation follow-up  
• 
Adverse events indicating possible mechanical failure or weakness of the HAV  
o Anastomotic rupture 
o Anastomotic bleeding  
o Spontaneous HAV rupture  
o Aneurysm  
o Pseudoaneurysm  
o Abnormal post cannulation hemostasis 
• 
HAV infections 
• 
Change from baseline of PRA and anti-HAV IgG levels (at 12 months) 

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• 
All AEs/SAEs until 12 months post implant, after that only SAEs associated with the HAV 
and adverse events of special interest. 
4.2.2 Efficacy Endpoints 
4.2.2.1 Primary Efficacy Endpoints – assessed at 3 months post implantation 
• 
Primary patency 
o Defined as being maintained until any intervention designed to maintain or 
reestablish patency, access thrombosis or the measurement of patency’, i.e., 
patent without interventions 
• 
Primary assisted patency 
o Defined as being maintained until access thrombosis or the time of measurement 
of patency, including intervening manipulations (surgical or endovascular 
interventions) designed to maintain the functionality of patent access’ i.e., patent 
without an intervention to clear a thrombus 
• 
Secondary patency 
o Defined as being maintained until access abandonment 
o Access abandonment defined as no remaining segment of the study conduit is 
incorporated into the vascular access circuit used for dialysis 
4.2.2.2 Secondary Efficacy Endpoints – assessed throughout the 36 month post 
implantation follow-up 
• 
Primary patency 
• 
Primary assisted patency 
• 
Secondary patency 
• 
Interventions required to achieve/maintain secondary patency. 
• 
Histopathological remodeling of any HAV (based on any samples collected). 
4.3 Duration of Study Participation 
Each subject will be followed at study specific visits until he/she has completed 12 months of 
follow-up after implantation (irrespective of patency status). After 12 months, subjects with a 
patent HAV will be followed (while the HAV remains patent) for up to 3 years (36 months) 
post-implantation at study visits every 6 months. 
The expected duration of the clinical investigation is 40 months (initiation of enrollment through 
completion of data collection). 

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5. STUDY POPULATION 
5.1 Description of the Study Population 
The study population will consist of subjects with ESRD who require hemodialysis and are 
targeted for implantation of an AV graft for dialysis access. 
5.1.1 Inclusion Criteria  
1. Subjects with ESRD who are not, or who are no longer candidates for creation of an 
autologous AV fistula and therefore need placement of an AV graft in the arm 
(upper- or forearm) for hemodialysis therapy. 
2. Already established on hemodialysis  
3. At least 18 years of age at Screening. 
4. Suitable arterial and venous anatomy for implantation of straight or looped conduits 
in either the forearm or upper arm (not crossing the elbow). 
5. Hemoglobin ≥ 8 g/dL and platelet count ≥ 100,000 cells/mm3 prior to Day 0 (within 
45 days). 
6. Other hematological and biochemical parameters within a range consistent with 
ESRD prior to Day 0 (within 45 days). 
7. Normal clotting (international normalized ration [INR] ≤ 1.5 or prothrombin time ≤ 18 
sec unless the patient is taking an anticoagulant for an approved indication at the 
time of HAV implantation. 
8. Female subjects must be either: 
a. Of non-childbearing potential, which is defined as post-menopausal (at least 
1 year without menses prior to Screening) or documented surgically sterile or 
post hysterectomy (at least 1 month prior to Screening) 
b. Or, of childbearing potential, in which case: 
i. Must have a negative serum or urine pregnancy test at Screening, 
and 
ii. Must agree to use at least one form of the following birth control 
methods for the duration of the study: 
1. Established use of oral, injectable or implanted hormonal 
methods of contraception 
2. Placement of an intrauterine device or intrauterine system 
3. Barrier methods of contraception: condom or occlusive cap 
(diaphragm 
or 
cervical/vault 
caps) 
with 
spermicidal 
foam/gel/film/cream/suppository 

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9. Subject, or legal representative, able to communicate effectively with investigative 
staff, competent and willing to give written informed consent, and able to comply with 
entire study procedures including all scheduled follow-up visits. 
10. Life expectancy of at least 1 year. 
5.1.2 Exclusion Criteria  
1. History or evidence of severe peripheral vascular disease in the intended arm for 
implantation. 
2. Known or suspected central vein stenosis or conduit occlusion on the ipsilateral side 
of the planned implantation, unless the stenosis is corrected prior to HAV 
implantation. 
3. Treatment with any investigational drug or device within 60 days prior to study entry 
(Day 0) or ongoing participation in a clinical trial of an investigational product. 
4. Cancer that is actively being treated with a cytotoxic agent. 
5. Documented hyper-coagulable 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 deep vein thrombosis, pulmonary 
embolism, etc.) within the 5 previous years. 
6. Spontaneous or unexplained bleeding diathesis clinically documented within the last 
5 years or a biochemical diagnosis (e.g. von Willebrand disease, etc.). 
7. Active clinically significant immune-mediated disease, not controlled by maintenance 
immunosuppression. 
a. Low dose glucocorticoid therapy (e.g. up to 10 mg a day prednisone or 
prednisolone) is acceptable. 
b. High dose glucocorticoid therapy for treatment of autoimmune flare, or other 
inflammatory diseases is excluded. 
c. Patients using glucocorticoids for immunosuppression post-transplant to 
prevent against transplanted allograft rejection in the period post allograft 
failure are excluded. 
d. The following examples of immunosuppressive agents (or the like) are 
exclusionary for enrollment in this clinical trial: 
i. tacrolimus or FK506 [Prograf] 
ii. mycophenolate mofetil [Cellcept],  
iii. cyclosporine [Sandimmune or Gengraf] 
iv. Sirolimus administered systemically (Sirolimus in drug eluting stents is 
NOT an exclusion) 

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8. Anticipated renal transplant within 6 months. 
9. Venous outflow from HAV cannot be placed more centrally than the venous outflow 
of any previous failed access on that extremity. 
10. Active local or systemic infection (white blood cells [WBC] > 15,000 cells/mm3 at 
Screening). If the infection resolves, the subject must be at least 1 week post 
resolution of that infection before implantation. 
11. Known serious allergy to planned antiplatelet agent. 
12. Pregnant women, or women intending to become pregnant during the course of the 
trial. 
13. Any other condition which in the judgment of the investigator would preclude 
adequate evaluation of the safety and efficacy of the HAV. 
14. Previous enrollment in this study or any other study with HAV. 
15. Employees of Humacyte and employees or relatives of the investigator. 
 
 

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6. INVESTIGATIONAL MEDICINAL PRODUCT 
6.1 Human Acellular Vessel 
6.1.1 Product Description 
The IMP is Humacyte’s HAV, which is a tissue-engineered vascular conduit for hemodialysis 
access in patients with ESRD. It is a sterile, non-pyrogenic acellular tubular conduit composed 
of human collagen types I and III plus other ECM proteins, including fibronectin and vitronectin. 
The HAV has an inner diameter of 6 mm and approximately 42 cm in length (~40 cm of usable 
length). The product is supplied on a silicone mandrel immersed in sterile, phosphate buffered 
saline with the bioreactor bag in which it was grown and decellularized, and this sterile 
bioreactor bag is sealed within a labeled plastic Peel Pak® container with Tyvek lid. 
Additional information on the manufacturing process and testing of HAV is provided in the 
Investigator Brochure.  
The IMP that was administered to subjects in Humacyte’s Phase 3 studies was produced by a 
contract manufacturing organization (AlloSource, Centennial, CO) using a bioreactor system 
capable of producing 10 HAV in a single batch. Humacyte has constructed a commercial 
manufacturing facility in Durham, North Carolina and has installed bioreactor systems in this 
new plant capable of producing 200 HAV in a batch. The fundamental aspects of the 
manufacturing process have remained unchanged. Human smooth muscle cells are seeded 
onto a tubular scaffold composed of poly-glycolic acid contained within a bioreactor container. 
Tissue culture medium is circulated through the bioreactor system that encourages growth of 
the cells within the scaffold. A cyclic, pulsatile force is delivered through the lumen of the tubular 
scaffold that causes the smooth muscle cells to secrete extracellular matrix proteins, resulting in 
a 3 dimensional tissue-engineered construct. Cellular material is removed from this construct by 
treatment with various chemical treatments, resulting in an acellular tubular implant that is 
contained in the bioreactor housing immersed in buffered saline solution. The commercial 
manufacturing systems have incorporated highly advanced process controls and automation in 
comparison with the previous systems used at AlloSource. However, HAV produced in the new 
plant in North Carolina using the larger scale commercial equipment will be shown to be 
biochemically and mechanically comparable to HAV produced previously prior to administration 
to subjects in this study.  
 
6.1.2 Manufacturer of the Investigational Medicinal Product 
The HAV is manufactured by: 

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Humacyte, Inc. 
 
2525 E. Highway 54 
Durham, NC 27713 
 
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. 
6.1.3 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. 
The HAV product unit is fixated within the box in a custom designed, thermoformed tray, with 
fittings to hold the tubing at either end and constrain the HAV product unit. A Tyvek lid material 
is then heat sealed to the top perimeter external surface of the tray to completely enclose the 
HAV product unit. The vessel container is stored and shipped in an opaque, non-corrugated, 
lacquer- coated cardboard outer box. The box prevents light penetration and its surfaces 
are non- shedding. The product is stored and shipped under controlled conditions validated to 
maintain temperature at approximately 4°C (range: 2 – 10°C).  
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 resistant label affixed to the secondary container will be used to 
ensure that the product is not compromised prior to use. 
6.1.4 Implantation of the Humacyte Human Acellular Vessel 
The Humacyte HAV is implanted using standard vascular surgical techniques similar to 
placement of synthetic or biologic AV grafts (see study manual and/or instructions for use 
document packaged with HAV for details).  
The HAV must be delivered through the subcutaneous tissue by means of a sheath tunneler. 
During tunneling, the HAV should be passed through the tunneler sheath with the silicone 
mandrel in place to facilitate ease of delivery (see study manual and/or instructions for use 
document packaged with HAV for details).  

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6.2 Investigational Medicinal Product Accountability Procedures 
6.2.1 Human Acellular Vessel 
HAVs will be provided by Humacyte. Documentation of receipt, dispensing, and return of the 
HAVs must be maintained by the Principal Investigator or his/her designee. It is the Principal 
Investigator’s responsibility to ensure that the HAVs are kept in a secure location, with access 
limited to individuals authorized by the Principal Investigator. The HAVs will be shipped by 
Humacyte or a designated representative with the IMP Shipment Confirmation Form. Once 
signed, the form should be returned to Humacyte, and the original will be maintained in the 
Investigator’s Files. The HAV Accountability Log will be used to account for all HAVs received, 
dispensed, and returned and must be maintained by the site until the conclusion of the study. 
Following final accountability of the HAVs by Humacyte or its authorized designee, all unused 
HAVs will be returned to Humacyte or destroyed according to procedures agreed upon with 
Humacyte. 
 
 

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7. OTHER TREATMENTS AND MEDICATIONS 
7.1 Prior and Concomitant Medications 
Prior medications are defined as all prescription medications plus aspirin taken within 7 days 
(whether continuing or not) prior to surgery (Day 0). All prior and concomitant medications 
(including immediately pre-surgery and post-surgery medications) must be listed in the subject’s 
medical record and recorded in the electronic case report form (eCRF) (as defined in Section 8).  
Drugs used during anesthesia should be recorded in the anesthesia records but should not be 
transcribed in the eCRF.  
Subjects should be questioned at each study visit concerning any new medications or changes 
in current medications (does not include IV fluids).  
For antibiotics, the following information will be recorded in the eCRF: 
• 
Medication generic name/components of combination product 
• 
Dose 
• 
Route of administration 
• 
Frequency of administration 
• 
Date started 
• 
Date stopped 
• 
Indication for use 
For all other concomitant medications taken during the study, only medication name, indication 
for use and start and stop dates will be recorded in the eCRF. Only prescription medications 
plus aspirin (including any combination drug containing aspirin) will be captured. 
7.2 Essential and Restricted Medications  
7.2.1 Essential Medications 
All subjects should receive both antibiotic and antithrombotic therapy in conjunction with HAV 
implantation: 
Antibiotic prophylaxis:  
All subjects must have at least 1 dose of antibiotic prophylaxis in accordance with local 
institutional guidelines. Longer antibiotic prophylaxis is at the discretion of the Principal 
Investigator.  

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Antithrombotic prophylaxis: 
Intra-operative heparin: This is not a requirement, but if heparin is used, the dose and route of 
administration of heparin during surgery are at the discretion of the investigator. 
Each subject will be required to take daily aspirin (75 to 325 mg) unless he/she is already taking 
another antiplatelet agent. Aspirin should be initiated no later than the day after surgical 
implantation of the HAV (Day 1). If low molecular weight heparin (LMWH) is administered post-
operatively, aspirin or other antiplatelet agent should be initiated after stopping LMWH. 
Aspirin is the recommended agent to be used for antiplatelet therapy and generally should not 
be combined with a second antiplatelet agent unless there is a specific indication for dual 
antiplatelet therapy (such as a drug eluting stent). Subjects who are known to be aspirin-
sensitive should take another antiplatelet agent at the discretion of the investigator. 
Anticoagulation is contraindicated unless there is a specific indication, such as deep vein 
thrombosis, pulmonary embolism, or atrial fibrillation. Patients already on anticoagulation at the 
time of screening for an appropriate medical indication can be enrolled in to the study, provided 
their screening data (INR, prothrombin time [PT]) at the time of medical director review indicates 
that it is being appropriately managed. Such patients do not require antiplatelet therapy with 
aspirin. Anticoagulation should be interrupted during a short perioperative window (as 
determined by standard of care for the site depending upon the indication for anticoagulation) 
and then resumed as soon as it is appropriate. If anticoagulation therapy ceases during the 
study the patient should start antiplatelet therapy (preferably with aspirin) as soon as possible. 
7.2.2 Restricted Medications  
Direct thrombin inhibitors, Factor Xa inhibitors, and vitamin K antagonists should only be given if 
there is a specific indication for their use.  

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8. STUDY PROCEDURES/EVALUATIONS 
8.1 Screening (Baseline) (Day -45 to Day 0) 
The screening period time window is currently specified as a maximum of 45 days from the day 
of consent until the day of surgery. In certain cases, the originally scheduled day of study 
surgery may need to be delayed due to purely logistical reasons and the subject's screening 
assessments may no longer fall within the current protocol-specified screening period time 
window. If there has been no significant change in the medical condition of the subject, it should 
not be necessary to repeat screening assessments or to reconsent the subject prior to study 
surgery. However, any extension of the screening period time window specified in the protocol, 
even though only for logistical reasons, must be discussed with and approved by the medical 
monitor prior to the day of study surgery. Patients who have had significant medical events 
since screening and are now outside of the original screening window will need to be 
rescreened. Any relevant clinical data collected as part of standard of care since the initial 
screening that is within the allowed window for surgery may be used for rescreening purposes. 
8.1.1 Informed Consent 
The 
subject’s 
informed 
consent 
must 
be 
obtained 
prior 
to 
any 
study-related 
procedures/activities, using the site’s Independent Ethics Committee (IEC) approved consent 
form. The informed consent will cover: 
• 
Agreement to participate in the trial for the full 3 years; 
• 
Willingness to have study-specific medical information collected if the subject desires to 
stop coming for study visits. It should be noted that consent for this information collection 
is not a requirement for participation in the study;  
• 
Willingness to have discarded parts of the implanted HAV collected for histology. It 
should be noted that consent for collection of histology is not a requirement for 
participation in the study. 
8.1.2 Demographics 
The subject’s age, gender, race and ethnicity will be recorded. 
8.1.3 Medical History 
A detailed medical history for each subject, including cause(s) of renal failure, history of dialysis 
and past vascular access procedures and smoking history will be obtained during Screening. All 
relevant past and present conditions that have occurred in the last 5 years will be recorded, as 
well as prior surgical procedures (including renal transplant history, if applicable). All conditions 

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for which the subject is currently taking medications or receiving ongoing therapies are 
considered a present condition and should be listed. 
8.1.4 Prior and Concomitant Medications 
All prescription medications and aspirin that the subject is taking during the study or has taken 
within 7 days prior to surgery must be recorded in the subject’s medical record and eCRF (see 
Section 7.1). 
8.1.5 Physical Exam, Vital Signs and Temperature 
A complete physical exam (PE) will be performed during Screening (including height and 
weight). The investigator or qualified medical personnel who routinely perform these evaluations 
in this patient population will conduct the examination, determine findings, and assess any 
abnormalities with respect to clinical significance. The subject’s sitting blood pressure, resting 
heart rate and temperature will also be obtained. The patient should be carefully examined for 
signs or symptoms of central vein pathology as well as assessment of adequate arterial inflow. 
Standard of care PEs conducted prior to consent may be used for determination of eligibility 
provided they are within the screening period time window and all required data are available. 
8.1.6 Electrocardiogram  
A 12-lead electrocardiogram (ECG) will be performed during Screening. A standard of care 
12-lead ECG completed prior to consent may be used for determination of eligibility provided it 
occurred within the screening period time window. 
8.1.7 Laboratory Evaluations 
During Screening blood will be collected for the following:  
• 
Hematology: hemoglobin, hematocrit, red blood cell (RBC), WBC with differential, 
platelet count. 
• 
Clinical chemistry: sodium, potassium, calcium, blood urea nitrogen (BUN) or urea, 
creatinine, albumin, total bilirubin, glucose (non-fasting). 
• 
Coagulation: INR or PT (if INR value is not available) 
• 
PRA 
• 
Anti-HAV IgG antibodies 

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Additionally, either a urine sample will be obtained for women of childbearing potential to 
perform a urine pregnancy dipstick test or a serum pregnancy test will be performed. 
Standard of care laboratory evaluations conducted prior to consent may be used for 
determination of eligibility provided they are within the screening period time window. 
8.1.8 Vessel Mapping 
Vessel mapping will be performed during Screening to determine whether the vessels in the 
operative limb are suitable for HAV implantation. Vessel mapping performed by ultrasound in 
the clinic by the investigator is acceptable. If adequate vessel mapping has been undertaken 
within the 8 weeks prior to the start of Screening and there has been no significant change in 
the condition of the subject (including insertion of CVC) then repeat vessel mapping is at the 
discretion of the Principal Investigator. 
8.1.9 Assessment of Central Vein Stenosis 
The absence of central vein stenosis will be determined by clinical criteria. If central vein 
stenosis or occlusion on the side in which implantation of the HAV is planned is 
identified/suspected, it must be corrected before implantation. 
8.1.10 Review of Subject Eligibility  
After review by the Principal Investigator, the subject’s Screening eCRFs will be provided to the 
Medical Monitor for review and confirmation of eligibility prior to implantation. 
8.1.11 Serious Adverse Events  
Only SAEs associated with screening procedures will be collected during the Screening period 
beginning from the time the subject signs the informed consent form. See Section 9 for 
information regarding AE/SAE collection and data handling. 
8.2 Surgical Placement of the HAV (Day 0) 
8.2.1 Medical History and Concomitant Medications 
The subject’s medical history and concomitant medications (prescription medications and 
aspirin use) will be updated (if changed) prior to surgery. Drugs used during anesthesia should 
be recorded in the anesthesia records but should not be transcribed in the eCRF. 
8.2.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) and document in eCRF subject’s temperature (at all 
visits irrespective of symptoms). The investigator or qualified medical personnel who routinely 

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perform these evaluations in this patient population will conduct the examination, determine 
findings, and assess any abnormalities with respect to clinical significance.  
8.2.3 Confirmation of Subject Eligibility  
After a subject completes the Screening assessments, the Principal Investigator will review the 
subject’s inclusion/exclusion criteria to determine the subject’s eligibility. The Screening pages 
of the eCRF for eligible subjects will then be reviewed and eligibility confirmed by the Medical 
Monitor prior to implantation.  
8.2.4 Surgical Placement 
The surgical procedure for implantation, including the location of the HAV, and any 
complications immediately postoperatively must be documented indicating whether subject 
remained in the hospital the night after surgery. If so, it has to be recorded whether the 
overnight stay was planned and whether it was related to the surgery or some other reason. 
8.2.5 Confirmation of Patency 
Patency of, and adequate flow in, the HAV will be confirmed intraoperatively or immediately 
post-surgery by the investigator’s preferred method (eg. PE, Doppler, ultrasound, etc.) and will 
be documented in the source documents and recorded in the eCRF.  
8.2.6 Adverse Events  
The subject will be asked general questions about his/her health and for any HAV or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.3 Postoperative Evaluation-Day 7-15 Visit  
The initial required postoperative visit will occur anytime from Day 7 to Day 15 and will include 
the following assessments: 
8.3.1 Concomitant Medications 
Changes in all concomitant prescription medications and aspirin use since last visit will be 
documented in the source documents and recorded in the eCRF  
8.3.2 Symptom-directed Physical Examination, including Temperature 
A symptom-directed PE (if needed) including subject’s temperature will be performed. The 
investigator or qualified medical personnel who routinely perform these evaluations in this 

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patient population will conduct the examination, determine findings, and assess any 
abnormalities with respect to clinical significance. 
8.3.3 Assessment of Surgical Site Healing 
A clinical examination of the surgical site should be conducted and the findings documented in 
the source documents and recorded in the eCRF Clinical Examination of HAV 
A clinical examination of the access site and HAV will be performed at all postoperative study 
visits. 
8.3.4  Assessment of Problems with the Access Site or HAV and HAV 
Interventions 
Any problems and interventions with the access site and HAV including infections and the 
occurrence of thrombosis must be documented. Any procedures performed or treatments, 
including reasons for the procedures and dates of hospitalization, will be documented in the 
source documents and recorded in the eCRF. 
8.3.5 Assessment of HAV Patency and Flow 
The patency of the HAV and adequacy of flow will be assessed by the investigator using the 
investigator’s preferred method (eg. palpation, stethoscope auscultation, Doppler, ultrasound, 
etc.) and will be documented in the source documents and recorded in the eCRF. 
8.3.6 Assessment of Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Information on subject hemodialysis since the last study visit, including frequency will be 
documented in the source documents and recorded in the eCRF. Additionally, information on 
CVC in place or if the subject had a CVC in place since the last visit will be documented in the 
source documents and recorded in the eCRF. Of particular interest is whether an alternate route 
for dialysis (CVC, peritoneal) is used and for how long. 
8.3.7 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any HAV or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.3.8 Assessment of Events of Special Interest 
Events of Special Interest are defined in Section 9.3, and the subject should be assessed at 
each postoperative study visit for these events. For each of these events detailed surgical notes 

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(with illustrative diagram), including reason for and outcome of any intervention or 
abandonment, should be entered into the eCRF expeditiously (within 48 hours). If the event 
meets the criteria for a SAE (as defined in Section 9.2), whether or not causally related to the 
IMP, the event must be reported by the investigator to Safety immediately (no later than 24 
hours after learning of its occurrence).  
Detailed information about the occurrence and treatment/intervention for these events will be 
collected throughout the study up to 3 years post-implantation. This information may include: 
• 
Summarized surgical notes, including a simplified anatomical diagram showing where 
angioplasties or revisions have been made (provided intervention worksheet) 
• 
Need for hospitalization (number of nights) 
• 
Need for antibiotics (in the case of access-related infections) 
Note: If all or part of the HAV is resected it should, whenever possible, be retained for future 
histological examination (if the subject provided his/her consent). 
8.4 Postoperative Evaluation-Day 28 (± 7D) Visit 
8.4.1 Concomitant Medications 
Changes in all concomitant prescription medications and aspirin use will be documented in the 
source documents and recorded in the eCRF. 
8.4.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) including subject’s temperature (at all visits 
irrespective of symptoms. The investigator or qualified medical personnel who routinely perform 
these evaluations in this patient population will conduct the examination, determine findings, 
and assess any abnormalities with respect to clinical significance. 
8.4.3 Assessment of Surgical Site Healing 
A clinical examination of the surgical site should be conducted and the findings documented in 
the eCRF. 
8.4.4 Clinical Examination of the Access Site and HAV 
A clinical examination of the access site and HAV will be performed at all postoperative study 
visits. 

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8.4.5 Assessment of any Problems with Access Site or HAV and HAV 
Interventions 
Any problems and interventions with the access site and HAV including infections and the 
occurrence of thrombosis must be documented. Any procedures performed or treatments, 
including reasons for the procedures and dates of hospitalization, will be documented in the 
source documents and recorded in the eCRF. 
8.4.6 Assessment of HAV Patency 
The patency of the HAV and adequacy of flow will be assessed by the investigator using the 
investigator’s preferred method (eg. palpation, stethoscope auscultation, Doppler, ultrasound, 
etc.). 
8.4.7 Duplex Ultrasound 
A duplex ultrasound will be performed to assess HAV patency, diameter of the lumen mid-
conduit, implant and anastomotic stenosis, volumetric flow rate, and to monitor for true 
aneurysm development. The full length of the HAV should be visualized with particular attention 
paid to any increase in diameter of the conduit that might indicate aneurysm formation. For 
purposes of this study, the full length of the HAV constitutes the entire conduit and includes both 
arterial and venous anastomoses. The methodology will be described in the study manual. 
8.4.8 Determination that the HAV may be used for Dialysis 
Beginning on Day 28 post-implantation (± 7 days), the investigator (or designee) should 
evaluate the HAV to determine if it is suitable to be used for dialysis. Such suitability will be 
recorded in the eCRF and transmitted to the dialysis center caring for that subject with guidance 
that cannulation of the HAV for dialysis should not start before 28 days post-implantation (earlier 
use of the HAV for dialysis for urgent clinical reasons may be permitted but must be approved 
prospectively by the medical monitor). 
If the HAV is deemed not ready for use, either the subject should be brought back to the site for 
a repeat assessment in a few weeks, or an intervention arranged. 
8.4.9 Assessment of Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Information on subject hemodialysis since the last study visit, including frequency will be 
documented in the source documents and recorded in the eCRF. Additionally, information on 
CVC in place or if the subject had a CVC in place since the last visit will be documented in the 
source documents and recorded in the eCRF. Of particular interest is whether an alternate route 
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8.4.10 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any HAV or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.4.11 Assessment of Events of Special Interest 
Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 9.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9.  
8.4.12 Laboratory Evaluations 
At Day 28 (± 7 days), a blood sample will be collected for the following:  
• 
Hematology: hemoglobin, hematocrit, RBC, WBC with differential, platelet count. 
• 
Clinical chemistry: sodium, potassium, calcium, BUN or urea, creatinine, albumin, total 
bilirubin, glucose (non-fasting). 
• 
PRA 
• 
Anti-HAV IgG antibodies 
8.5 Postoperative Evaluations (Month 2 to Month 12) 
8.5.1 Evaluations and Procedures to be performed at All Study Visits from Month 
2 to Month 12 
The following assessments will be performed at the Month 2 (± 7 days), Month 3 (± 7 days), 
Month 6 (± 14 days), and 12 (± 14 days), visits: 
8.5.1.1 Concomitant Medications 
All concomitant prescription medications and aspirin taken during the study up to Month 12 will 
be recorded in the eCRF. 
8.5.1.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) including subject’s temperature (at all visits 
irrespective of symptoms. The investigator or qualified medical personnel who routinely perform 
these evaluations in this patient population will conduct the examination, determine findings, 
and assess any abnormalities with respect to clinical significance. 

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8.5.1.3 Clinical Examination of the Access Site and HAV 
A clinical examination of the access site and HAV will be performed at all postoperative study 
visits. 
8.5.1.4 Assessment of HAV Patency 
The patency of the HAV and adequacy of flow will be assessed by the investigator using the 
investigator’s preferred method (eg. PE[ie. palpation, stethoscope auscultation], Doppler exam, 
ultrasound imaging, etc.). 
8.5.1.5 Assessment of any Problems with the Access Site and HAV and 
Interventions, Including Events of Special Interest 
Any problems and interventions with the access site and HAV including infections and the 
occurrence of thrombosis must be documented. Any procedures performed or treatments, 
including reasons for the procedures and dates of hospitalization, will be documented in the 
source documents and recorded in the eCRF. 
Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 9.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9. If the HAV is abandoned, the reason for abandonment will be 
documented in the eCRF. 
8.5.1.6 Duplex Ultrasound 
A duplex ultrasound will be performed to assess HAV patency, diameter of the lumen mid-
conduit, implant and anastomotic stenosis, volumetric flow rate, and to monitor for aneurysm 
development. The full length of the HAV should be visualized with particular attention paid to 
any increase in diameter of the HAV that might indicate aneurysm formation. 
8.5.1.7 Determination that the HAV may be used for Dialysis (if not previously 
approved) 
The investigator should evaluate the HAV to determine if it is suitable to be used for dialysis. 
Such suitability will be recorded in the eCRF and transmitted to the dialysis center caring for that 
subject with guidance that cannulation of the HAV for dialysis should not start before 28 days 
post-implantation. 
8.5.1.8 Assessment of Hemodialysis and Placement and/or Removal of CVC 
Information if the subject underwent hemodialysis since the last study visit, including frequency 
will be documented in the source documents and recorded in the eCRF. Additionally, 
information if the subject has a CVC in place or if the subject had a CVC in place since the last 

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visit will be documented in the source documents and recorded in the eCRF. Of interest is 
whether an alternate route for dialysis (CVC, peritoneal) is used and for how long. 
8.5.1.9 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any HAV or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.5.2 Evaluations and Procedures to be performed only at Specific Visits from 
Month 2 to Month 12 
8.5.2.1 Removal of CVC that was in place Pre-implantation: Month 2 and 3 
The date and reason for removal of the CVC that was in place pre-implantation, if applicable, 
will be documented in source data and recorded in eCRF. 
8.5.2.2 PRA and Anti-HAV IgG Antibodies: Month 2, 6, and 12  
A blood sample will be collected for the PRA and Anti-HAV IgG antibodies evaluation.  
8.5.2.3 Laboratory Data: Month 2 
At Month 3 a blood sample will be collected for the following:  
• 
Hematology: hemoglobin, hematocrit, RBC, WBC with differential, platelet count. 
• 
Clinical chemistry: sodium, potassium, calcium, BUN or urea, creatinine, albumin, total 
bilirubin, glucose (non-fasting) 
8.6 Long Term Follow Up Post Month 12 through Month 36 
Evaluations and Procedures 
After 12 months, only subjects with a patent HAV will be followed for up to 3 years (36 months) 
post-implantation at study visits every 6 months. 
8.6.1 Evaluations and Procedures that will be performed at All Study Visits Post 
Month 12 to Month 36 (± 1M) 
8.6.1.1 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) including subject’s temperature (at all visits 
irrespective of symptoms. The investigator or qualified medical personnel who routinely perform 

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these evaluations in this patient population will conduct the examination, determine findings, 
and assess any abnormalities with respect to clinical significance. 
8.6.1.2 Clinical Examination of Access Site and HAV 
A clinical examination of the access site and HAV will be performed at all post Month 12 study 
visits. 
8.6.1.3 Assessment of HAV Patency 
The patency of the HAV and adequacy of flow will be assessed by the investigator using the 
investigator’s preferred method (eg. palpation, stethoscope auscultation, Doppler exam, 
ultrasound imaging, etc.). This assessment is not required for HAV that have been abandoned. 
8.6.1.4 Assessment of any Problems with the Access Site or HAV and 
Interventions, Including Events of Special Interest 
Any problems and interventions with the access site and HAV including infections and the 
occurrence of thrombosis must be documented. Any procedures performed or treatments, 
including reasons for the procedures and dates of hospitalization, will be documented in the 
source documents and recorded in the eCRF. 
Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 9.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9. If the HAV is abandoned, the reason for abandonment will be 
documented in the eCRF. 
8.6.1.5 Determination that the HAV may be used for Dialysis (if not previously 
approved) 
The investigator should evaluate the HAV to determine if it is suitable to be used for dialysis. 
Such suitability needs to be recorded in the eCRF and transmitted to the dialysis center caring 
for that subject. 
8.6.1.6 Assessment of Hemodialysis and Placement and/or Removal of CVC 
Information if the subject underwent hemodialysis since the last study visit, including frequency 
will be documented in the source documents and recorded in the eCRF. Additionally, 
information if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit will be documented in the source documents and recorded in the eCRF. Of particular 
interest is whether an alternate route for dialysis (CVC, peritoneal) is used and for how long. 

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8.6.1.7 Duplex Ultrasound  
A duplex ultrasound will be performed to assess HAV patency, diameter of the lumen mid-
conduit, implant and anastomotic stenosis, volumetric flow rate, and to monitor for aneurysm 
development. The full length of the HAV should be visualized with particular attention paid to 
any increase in diameter of the HAV that might indicate aneurysm formation. 
8.7 Early Termination Visit 
If a subject discontinues from the study before the Month 36 visit, then every effort should be 
made to perform the following early termination (ET) visit assessments: 
- 
Patients withdrawn prior to Month 12 should complete an ET that correlates with the 
procedures at Month 12.   
- 
Patients withdrawn after Month 12 and prior to Month 36 should complete an ET visit 
that correlates with procedures post Month 12 through Month 36.  
8.7.1 Concomitant Medications (if prior to month 12) 
Any changes to the subject’s prescription medications and aspirin use will be documented in 
source data and recorded in eCRF. 
8.7.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) including subject’s temperature (at all visits 
irrespective of symptoms. The investigator or qualified medical personnel who routinely perform 
these evaluations in this patient population will conduct the examination, determine findings, 
and assess any abnormalities with respect to clinical significance. 
8.7.3 Clinical Examination of the Access Site and HAV 
A clinical examination of the access site and HAV will be performed. 
8.7.4 Assessment of HAV Patency 
The patency of the HAV and adequacy of flow will be assessed by the investigator using the 
investigator’s preferred method (eg. palpation, stethoscope auscultation, Doppler, ultrasound, 
etc.). 
8.7.5 Assessment of any Problems with the Access Site or HAV and 
Interventions, Including Events of Special Interest 
Any problems and interventions with the access site and HAV including infections and the 
occurrence of thrombosis must be documented. Any procedures performed or treatments, 
including reasons for the procedures and dates of hospitalization, will be documented in the 

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source documents and recorded in the eCRF.Subjects should be assessed for the occurrence 
of Events of Special Interest as defined in Section 9.3. Detailed information about each of these 
events will be recorded in the eCRF as described in Section 8.3.9. If the HAV is abandoned, the 
reason for the abandonment will be documented in the eCRF. 
8.7.6 Duplex Ultrasound 
A duplex ultrasound should be performed to assess HAV patency, diameter of the lumen mid-
conduit, implant and anastomotic stenosis, volumetric flow rate, and to monitor for aneurysm 
development. The full length of the HAV should be visualized with particular attention paid to 
any increase in diameter of the HAV that might indicate aneurysm formation. 
8.7.7 Assessment of Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Information if the subject underwent hemodialysis since the last study visit, including frequency 
will be documented in the source documents and recorded in the eCRF. Additionally, 
information if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit will be documented in the source documents and recorded in the eCRF. Of particular 
interest is whether an alternate route for dialysis (CVC, peritoneal) is used and for how long. 
8.7.8 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any HAV or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.7.9 PRA and Anti-HAV IgG Antibodies (if prior to month 12) 
A blood sample to measure PRA and anti-HAV IgG antibody levels must be collected. 
8.8 Collection and Processing of Laboratory Samples 
Details concerning sample collection and processing can be found in the Study Manual. 
 
 

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9. SAFETY ASSESSMENTS AND ADVERSE EVENTS 
The safety of the HAV will be assessed in terms of the following: 
• 
Anastomotic rupture 
• 
Anastomotic bleeding  
• 
HAV spontaneous rupture 
• 
Aneurysm 
• 
Pseudoaneurysm 
• 
HAV infection 
• 
Increase from baseline in PRA/Anti-HAV IgG antibodies 
• 
Need for HAV revision or removal 
• 
Other AEs 
• 
Laboratory parameters (clinical chemistry and hematology) 
9.1 Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in a subject administered an IMP or has 
undergone study procedures and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of the IMP, whether or not 
related to the IMP.  
An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, ECG data, 
PE) should be defined as an AE only if the abnormality meets 1 of the following criteria: 
• 
Induces clinical signs or symptoms 
• 
Requires active intervention 
• 
Requires removal or abandonment of the HAV 
• 
The abnormality or test result is clinically significant in the opinion of the investigator. 
9.2 Definition of Serious Adverse Events 
An AE is considered “serious” if, in the view of either the investigator or Sponsor, it:  
• 
Results in death. 
• 
Is life threatening (An AE is considered “life-threatening” if, in the view of either the 
investigator or Sponsor, its occurrence places the subject at immediate risk of death. It 
does not include an adverse event that, had it occurred in a more severe form, might 
have caused death). 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the 
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• 
Results in congenital anomaly or birth defect. 
• 
Requires inpatient hospitalization or leads to prolongation of hospitalization 
(hospitalization for treatment/observation/examination caused by AE is to be considered 
as serious). 
• 
Represents a medically important event as determined by the investigator. 
Medical and scientific judgment should be exercised in deciding whether AEs are serious, such 
as important medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject and may require medical or surgical intervention 
to prevent one of the other outcomes listed in the definition above. These events, including 
those that may result in disability/incapacity, should also usually be considered serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or 
development of drug dependency or drug abuse. 
Note: Hospitalization for the surgical placement of the HAV will not be considered an SAE. 
However, prolongation of the initial hospitalization due to an AE will be considered a SAE. 
9.2.1 Suspected Unexpected Serious Adverse Reactions  
A suspected unexpected serious adverse reaction (SUSAR) is any adverse drug reaction that is 
serious, unexpected and suspected, meaning there is a reasonable possibility that the IMP 
caused the adverse event. An AE or suspected adverse reaction is considered "unexpected" if it 
is not listed in the Investigator Brochure or is not listed at the specificity or severity that has 
been observed. 
9.3 Events of Special Interest 
Events of Special Interest related to interventions and infections will be evaluated and include 
the following: 
• 
Events resulting in HAV abandonment 
• 
HAV thrombosis 
• 
HAV infection 
• 
HAV aneurysm (HAV lumen diameter > 9 mm ) formation  
• 
Clinically significant HAV pseudoaneurysm (clinically significant defined as requiring a 
surgical or radiological intervention) 
• 
HAV spontaneous rupture 
o Iatrogenic injuries are not an Event of Special Interest and should be reported as 
an AE 
• 
Events resulting in HAV revision or ligation  

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• 
Events resulting in HAV removal 
• 
Clinically significant stenosis of HAV (clinically significant defined as severity of severe 
or greater, or requiring a surgical or radiological intervention) 
• 
Clinically significant Steal Syndrome (clinically significant defined as severity of severe 
or greater, or requiring a surgical or radiological intervention) 
• 
Anastomotic bleeding 
• 
Anastomotic rupture 
 

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9.4 Criteria for Determining Causal Relationship to the HAV and 
Criteria for Determining Casual Relationship to Index Surgical 
Procedure 
The criteria for determining the causal relationship of an AE with the HAV is presented in the 
table below. A separate assessment of causal relationship of an AE to the HAV implantation 
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. 
Causal 
Relationship to the 
HAV 
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 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 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 
events). Although an adverse effect may rate only as “possible” soon 
after discovery, it can be flagged as requiring more information and 
later be upgraded to probable or 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 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 subject was not exposed to the HAV or, another 
cause is obvious and in which there is sufficient information that the 
etiology of the event is not related to the HAV. 
 

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9.5 Criteria for Defining the Severity of an Adverse Event 
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. 
9.6 Reporting of Adverse Events 
At each evaluation, the subject will be questioned in a general way and no specific symptoms 
will be suggested. If any AEs have occurred, they will be recorded on the AE pages of the eCRF 
and in the subject’s medical record. If known, the diagnosis should be recorded in preference to 
the listing of individual signs and symptoms.  
During the Screening period (Day -45 to Day 0 prior to implantation), only SAEs related to study 
procedures will be reported beginning at the time the subject signs the informed consent form. 
From Day 0 after implantation to 1 year post-implantation (Month 12 visit) or ET visit, whichever 
occurs earlier, all AEs will be reported. 
 
 

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During the long-term follow-up period from 1 year to 3 years post-implantation, only the 
following will be reported by the investigator: 
• 
All related SAEs  
• 
All Events of Special Interest (as defined in Section 9.3).   
9.6.1 Reporting of Serious Adverse Events 
Any SAE (as defined in Section 9.2) which occurs from Day 0 after implantation to 1 year post-
implantation (Month 12 visit) or ET visit, whichever occurs earlier, whether or not causally 
related to the IMP, must be reported by the investigator to Humacyte or designee immediately 
(no later than 24 hours after learning of its occurrence). Any related SAE during the long-
term follow-up period from 1 year to 3 years post-implantation must be reported by the 
investigator to Humacyte or designee immediately (no later than 24 hours after learning of its 
occurrence). Events of special interest should follow the same reporting time frame as SAEs. 
CTI Global Safety & Pharmacovigilance 
SAE Telephone Hotline:  
1.877.755.0742 
SAE eFax #:  Country-specific fax numbers will be provided in the study manual 
E-mail:  
 
 
CTISafety@ctifacts.com 
If there are any questions, or if clarification is needed regarding the SAE, please contact the 
Medical Monitor (see Section 1).  
Follow-up information for the event should be sent promptly (within 7 days of the initial 
notification). 
Full details of the SAE should be recorded on the medical records and in the eCRF. 
The following minimum information is required: 
• 
Study number,  
• 
Subject number, gender and age, 
• 
The date of report, 
• 
A description of the SAE (event, seriousness of the event), and 
• 
Causal relationship to the HAV. 

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Humacyte or Humacyte's designee will submit expedited safety reports to the regulatory 
agencies and IECs as necessary according to the timelines provided in the Safety Management 
Plan and will inform the investigators of such regulatory reports.  
9.6.2 Monitoring and Reporting of Serious Adverse Events Not Related to the 
HAV 
Patients with ESRD have significant co-morbidities and typically experience many SAEs related 
to those co-morbidities that are not related to the HAV. Investigators will be asked, as part of 
their reporting, to identify whether a particular SAE is HAV-related.   
For those events identified as not being related to the HAV, Humacyte will monitor these events 
for any increase in frequency that may indicate a link to the HAV. Occurrences of non-HAV 
related SAEs will be excluded from expedited reporting to the applicable regulatory authorities 
and to IECs. If aggregate analysis of these events indicates they occur more frequently with the 
HAV than expected, an expedited safety report may be submitted. 
9.6.3 Follow-Up of Adverse Events 
If any AEs are present when a subject completes 1 year post-implantation 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. Every effort should be made by the investigator or delegate 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. 
9.7 Reporting of Pregnancy 
If a study participant becomes pregnant during study participation, basic information about the 
pregnancy will be recorded in the Pregnancy eCRF and submitted to Safety. If there are 
complications during the pregnancy, the complications are recorded as AEs. The participant will 
be asked to report the outcome of the pregnancy and the site should submit the information to 
Safety within 30 days after the outcome of the pregnancy. 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. 

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9.8 Study Suspension and Stopping Criteria 
All SAEs that may indicate acute HAV infection (<30 days post-implant), mechanical failure of 
the HAV, or inflammatory/immune response to the HAV will be notified within 72 hours to the 
DMC chair who will consider whether a formal review of study continuation should be 
undertaken. The DMC chair will respond to Humacyte regarding the need for a safety review 
within 48 hours. If such a review is deemed necessary by the DMC chair recruitment into the 
study will be placed on hold until that review is complete. The sites will be notified by fax or e-
mail of any such hold on recruitment. 
9.9 Data Monitoring Committee  
An independent Data Monitoring Committee (DMC) will be established to review safety on an 
ongoing basis and to provide recommendations about stopping, continuing or otherwise 
modifying the study. The DMC will consist of individuals who are not directly involved in the 
conduct of the study. The DMC will review data from this study on an ongoing basis with the 1st 
scheduled DMC review after the last patient completes Month 3 and every 6 months thereafter. 
A separate charter will be established that will describe 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. 
9.10 New Information Affecting the Conduct of the Study 
When new information becomes available for conducting the clinical study properly, Humacyte 
or designee will inform all investigators involved in the clinical study as well as the regulatory 
authorities and IECs.  
10. STATISTICAL CONSIDERATIONS 
This is a prospective, two center, open label, single arm study with no formal hypothesis testing. 
Data will be summarized using descriptive statistics only.  
All available data will be summarized and reported in a Clinical Study Report (CSR) when the 
last patient completes 3 months of follow up. A second analysis will be conducted when all 
patients have completed 12 months of follow up. The final analysis will occur when the final 
patient completes 36 months of follow up. Details of data handling and planned descriptive 
statistics are in the Statistical Analysis Plan. 

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11. STUDY MANAGMENT AND DATA COLLECTION 
11.1   Ethical Conduct of the Trial 
This study will be conducted according to the protocol; applicable national regulations; the 
World Medical Association Declaration of Helsinki and Good Clinical Practice (GCP), as per 
International Conference on Harmonization (ICH) E6 guidelines. Each investigator will conduct 
the trial according to applicable local or regional regulatory requirements. 
11.2 Subject Confidentiality 
Individual subject medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited. Such medical information may be given 
only after approval of the subject to the subject’s physician or to other appropriate medical 
personnel responsible for the subject’s well-being. 
Personal subject data will be kept confidential in compliance with the European Union 
General Data Protection Regulation 2016/679 and other applicable international and 
national requirements.  
Humacyte shall not disclose any confidential information on subjects obtained during the 
performance of their duties in the clinical study without justifiable reasons. 
Humacyte affirms the subject’s right to protection against invasion of privacy. Only a subject 
identification number and/or initials (where allowed by local or national regulations) will identify 
subject data retrieved by Humacyte. However, Humacyte requires the Investigator to permit 
Humacyte, Humacyte’s representative(s), the IEC and when necessary, representatives of the 
regulatory health authorities to review and/or to copy any medical records relevant to the study. 
Humacyte will ensure that the use and disclosure of protected health information obtained 
during a research study complies with the federal and/or regional legislation related to the 
privacy and protection of personal information. 
11.3   Independent Ethics Committee  
Independent Ethics Committees (IECs) must be constituted according to the applicable 
requirements, including ICH GCP. 
It is the responsibility of each Principal Investigator (or designee such as the CRO) to submit the 
protocol, Investigator Brochure, subject informed consent, subject recruitment materials (if 
applicable), and other documentation as required by the IEC to his/her IEC for review and 
approval. A copy of the written approval must be provided to the CRO. The documentation 

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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 and a list of current membership, or letter from the IEC stating that 
the membership list is on file, must be obtained from the IECs 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 IEC 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 IEC. This 
includes notification to the IEC regarding protocol amendments, updates to the subject informed 
consent, recruitment materials intended for viewing by subjects, expedited safety reports, SAEs 
and unexpected AEs, reports and updates regarding the ongoing review of the trial at intervals 
specified by the respective IEC, and submission of final study reports and summaries to the 
IEC. 
11.4   Subject Informed Consent 
Subjects must sign and date an IEC-approved informed consent form prior to any study 
procedures being performed. Each subject will receive a signed and dated copy of the informed 
consent. In addition, this information should be recorded in the subject’s medical record (i.e., 
source document).  
The subject will be asked to sign for 3 aspects of the study: consent to participate in the study, 
consent to allow the study doctor to follow-up with his/her health care providers in the event the 
subject decides to stop attending study visits and consent to allow for study doctors to collect 
any samples or HAVs to be used for histology. It should be noted that the consent for collection 
of histology is not a requirement for participation in the study. 
The written consent document will embody the elements of informed consent as described in 
the World Medical Association Declaration of Helsinki, applicable national regulations, GCP 
(ICH E6 guideline), and in accordance with any local regulations. The investigator (or designee 
such as the CRO) is responsible for the preparation, content and IEC approval of the informed 
consent document. The consent form must be approved by the site’s IEC and be acceptable to 
Humacyte. 
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 IEC. Subjects must be given ample opportunity to 
inquire about details of the study. 

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11.5 Substantial Amendments to the Protocol 
A substantial amendment must be agreed to in writing by Humacyte and submitted to and 
approved by the respective regulatory authority and IEC 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 subject; however, 
approval must be obtained as soon as possible thereafter. Any amendments must also be 
signed by the Principal Investigator. 
11.6 Study Initiation 
The Principal Investigator must not enroll any subjects 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 investigator will not be 
supplied with IMP until all necessary pre-study requirements have been completed and signed 
essential documents provided to the CRO. 
11.7 Study Monitoring 
It is the responsibility of the Principal 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 in 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. 
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. 

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11.8 Case Report Form  
An eCRF will be used for this study. The data will be entered in the eCRF in a timely manner on 
an ongoing basis.  
The Principal Investigator is responsible for ensuring that data are properly recorded in each 
subject’s eCRF and related documents. The Principal Investigator 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 Humacyte. 
11.8.1 Data Management 
Data management will be coordinated with Humacyte or designee in accordance with the SOPs 
for Data Management. All study specific processes and definitions will be documented by Data 
Management. eCRF completion and correction processes will be referenced in the eCRF 
instructions. Coding of medical terms will be performed using the Medical Dictionary for 
Regulatory Activities. 
11.9 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. 
11.10 Retention of Records 
All documentation pertaining to the study will be kept by Humacyte or its designee in 
accordance with ICH guidelines and applicable national and local regulations. 
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 IMP disposition to enable evaluations or audits from 
regulatory authorities and Humacyte or its designees. These documents are to be retained until 

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at least 2 years after the last approval of a marketing application in an ICH region and until there 
are no pending or contemplated marketing applications in an ICH region, or at least 2 years 
have elapsed since the formal discontinuation of clinical development of the investigational 
product. However, these documents should be retained for a longer period if required by the 
applicable regulatory requirements or if needed by Humacyte. Humacyte will notify the 
site/investigator if the marketing application is approved or if the IND/Investigational Medicinal 
Product Dossier is discontinued. The investigator agrees to obtain Humacyte's agreement prior 
to disposal, moving, or transferring of any study-related records. Humacyte will archive and 
retain all documents pertaining to the study according to local regulations. 
Data generated by the methods described in the protocol will be recorded in the subjects' 
medical records. All data will be entered into the eCRFs supplied for each subject. 
11.11 Protocol Deviations 
A protocol deviation is any noncompliance with the protocol or associated 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 Humacyte and the 
IEC 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 Humacyte who will agree on the 
necessary actions to be taken. 
If required per their guidelines, reports about protocol deviations must be provided to the local 
IEC. 
11.12 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 subject accordingly.  
11.13 Audit 
It is the responsibility of Humacyte or designee 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. Authorized 

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representatives from Humacyte, regulatory authorities and IEC will be granted access to the site 
and relevant study documentation to perform audits or inspections. The Principal Investigator 
should contact Humacyte immediately if contacted by a regulatory agency about an inspection 
involving this protocol. 
 
 

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12. REPORTING 
Following completion of follow-up of all subjects to the 3-month endpoint, a CSR 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. Addenda to the report will be generated and submitted to regulatory authorities 
that will include data up to 12 months, and then up to 36 months follow-up or based on timing 
otherwise to be defined.  
12.1 Quality Control and Quality Assurance 
Following written SOPs, 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 
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 Humacyte, and 
inspection by local and regulatory authorities. 
Quality control procedures will be implemented for data entry and data quality control checks 
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 subjects 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 subject’s decision 
to participate throughout the clinical investigation 
• 
Avoids any coercion or undue improper influence on, or inducement of, the subject to 
participate 
• 
Does not waive or appear to waive the subject’s legal rights  
• 
Uses native non-technical language that is understandable to the subject  
• 
Provides ample time for the subject to read and understand the informed consent form 
and to consider participation in the clinical investigation  
• 
Provides the subject 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 
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• 
Propose to Humacyte any appropriate modification(s) of the protocol 
• 
Refrain from implementing any modifications to the protocol without agreement from 
Humacyte, IEC, 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 
Humacyte in the eCRFs and in all required reports 
• 
maintain the IMP accountability records 
• 
Allow and support Humacyte 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 IEC when performing auditing activities 
• 
Ensure that all clinical-investigation-related records are retained as specified in this 
protocol 
13.3 Medical Care of Subjects 
The Principal Investigator shall: 
• 
Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical investigation in the case of AEs 
• 
Inform the subject of the nature and possible cause of any AEs experienced  
• 
Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required 

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• 
Provide the subject 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 subject is enrolled in a 
particular clinical investigation 
• 
Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation  
• 
Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from the clinical investigation while fully respecting the subject’s rights  
13.4 Safety Reporting 
The Principal Investigator shall: 
• 
Record every AE together with an assessment, in accordance with Section 9 of this 
protocol 
• 
Report to Humacyte, without unjustified delay, all SAEs and medically significant events 
as specified in Section 9.2 of this protocol 
• 
Supply Humacyte or designee, upon Humacyte’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 
Humacyte may suspend or prematurely terminate either a clinical investigation (study) at an 
individual investigative site or the entire clinical investigation for significant and documented 
reasons.  
A Principal Investigator, IEC, 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 subjects arises during the clinical investigation, or when 
so requested by the IEC or regulatory authorities, Humacyte shall suspend the clinical 
investigation while the risk is assessed. Humacyte shall terminate the clinical investigation if an 
unacceptable risk is confirmed.  
Humacyte shall consider terminating or suspending the participation of a particular investigation 
site or investigator 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, Humacyte suspends or prematurely terminates the investigation at an 
individual investigation site, Humacyte shall inform the responsible regulatory authority if 
required and ensure that the IEC is notified. If the suspension or premature termination was due 
to a safety-related reason, Humacyte shall inform all other principal investigators.  
If suspension or premature termination occurs,  
1. Humacyte shall remain responsible for providing resources to fulfill the obligations from the 
protocol and existing agreements for following up the subjects enrolled in the clinical 
investigation, and  
2. the Principal Investigator or authorized designee shall promptly inform the enrolled 
subjects 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 
Information concerning the IMP, patent applications, processes, unpublished scientific data, the 
Investigator Brochure and other pertinent information is confidential and remains the property of 
Humacyte. Details should be disclosed only to the persons involved in the approval or conduct 
of the study. The investigator may use this information for the purpose of the study only. It is 
understood by the investigator that Humacyte will use the information obtained during the 
clinical study in connection with the development of the IMP and therefore may disclose it as 
required to other clinical investigators or to regulatory agencies. In order to allow for the use of 
the information derived from this clinical study, the investigator understands that he/she has an 
obligation to provide Humacyte with all data obtained during the study. 
The study will be considered for publication or presentation at (scientific) symposia and 
congresses. A Publication Committee comprising a selected group of investigators, a statistician 
and a representative from Humacyte will oversee all publication of data from this study. 
Members of this committee will fulfill the criteria of the International Committee of Medical 
Journal Editors for authorship of a scientific publication in relation to this study.  
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 a sufficient time to allow 
Humacyte to seek patent protection of the invention.   
The first publication or disclosure of the results of this study will be a complete, joint multicenter 
publication or disclosure. Subsequent publication or presentation of data (entire or a subset) 
from the study will be permitted provided that the first publication is adequately referenced.  
 
 

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16. REFERENCES 
Allemang MT, Schmotzer B, Wong VL, et al. Heparin bonding does not improve patency of 
polytetrafluoroethylene arteriovenous grafts. Ann Vas Surg 2014;28:28-34. 
Bray BD, Boyd J, Daly C, et al. Vascular access type and risk of mortality in a national 
prospective cohort of haemodialysis patients. QJM 2012;105:1097-103. 
CDC. Dialysis Event Surveillance Manual. In: Network NHS, ed.: CDC; 2013. 
Dahl SL, Kypson AP, Lawson JH, et al. Readily available tissue-engineered vascular grafts. Sci 
Transl Med 2011;3:68ra9. 
Dember LM, Beck GJ, Allon M, et al. Effect of clopidogrel on early failure of arteriovenous 
fistulas for hemodialysis: a randomized controlled trial. JAMA 2008;299:2164-7. 
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. 
ERA-EDTA Registry. Renal replacement therapy in Europe: a summary of the 2011 ERA-EDTA 
Registry Annual Report. Clin Kidney J 2014;7:227-38. 
Haskal ZJ, Trerotola S, Dolmatch B, et al. Stent graft versus balloon angioplasty for failing 
dialysis-access grafts. N Engl J Med 2010;362:494-503. 
Huber 
TS, 
Carter 
JW, 
Carter 
RL, 
Seeger 
JM. 
Patency 
of 
autogenous 
and 
polytetrafluoroethylene upper extremity arteriovenous hemodialysis accesses: a systematic 
review. J Vasc Surg 2003;38:1005-11. 
Lawson JH, Glickman MH, Ilzecki M, Jakimowicz T, Jaroszynski A, Peden EK, et al. 
Bioengineered human acellular vessels for dialysis access in patients with end-stage renal 
disease: two Phase 2 single-arm trials. Lancet. 2016 May 20;387(10032):2026-34. 
Miller DC, Haberstroh KM, Webster TJ. PLGA nanometer surface features manipulate 
fibronectin interactions for improved vascular cell adhesion. J Biomed Mater Res A 
2007;81:678-84. 
Nassar GM, Ayus JC. Infectious complications of the hemodialysis access. Kidney Int 
2001;60:1-13. 
National Kidney Foundation. 2014 Annual Data Report: Epidemiology of Kidney Disease in the 
United States. Bethesda, MD2014. 
National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Vascular Access. Am J 
Kidney Dis 2006;48:S248-73. 
Quint C, Kondo Y, Manson RJ, Lawson JH, Dardik A, Niklason LE. Decellularized tissue-
engineered blood vessel as an arterial conduit. Proc Natl Acad Sci USA 2011;108:9214-9. 

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Roy-Chaudhury P, Kelly BS, Miller MA, et al. Venous neointimal hyperplasia in 
polytetrafluoroethylene dialysis grafts. Kidney Int 2001;59:2325-34. 
Ryan SV, Calligaro KD, Scharff J, Dougherty MJ. Management of infected prosthetic dialysis 
arteriovenous grafts. J Vasc Surg 2004;39:73-8. 
Shemesh D, Goldin I, Hijazi J, et al. A prospective randomized study of heparin-bonded graft 
(Propaten) versus standard graft in prosthetic arteriovenous access. J Vasc Surg 2015;62:115-
22. 
Sidawy AN, Gray RG, Besarab A, et al. Recommended standards for reports dealing with 
arteriovenous hemodialysis access. J Vasc Surg 2002;2002:603-10. 
Smith MP, Spark JI, Patel JV, Border DJ, Oswal D, Lewington AJ. Massive aneurysmal 
dilatation of a depopulated ureteric hemodialysis xenograft. Hemodial Int 2009;13:3-5. 
Thompson PC, Stirling CM, Geddes CC, Morris ST, Mactier RA. Vascular access in 
haemodialysis patients: a modifiable risk factor for bacteraemia and death. QJM 2007;100:415-
22. 
Zea N, Menard G, Le L, et al. Heparin-bonded polytetrafluorethylene does not improve 
hemodialysis arteriovenous graft function.  Ann Vasc Surg 2016;30:28-33. 
 
 
 
 
 
 

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APPENDIX 1:  VISIT SCHEDULE 
 
 
 
Screening 
D -45 to D 
0 
D 0 
 
D79 
D 28 
M 2 
M 3 
M 6 
M 12 
M 18-36 at 
6M 
intervals 
 
ET10 
Visit Window 
-- 
-- 
+8 D 
±7 D 
±7 D 
±7 D 
±14 D 
±14 D 
±1 M 
 
-- 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
Concomitant medications1 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Physical exam and temperature2 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
 
(X) 
ECG (12-lead) 
X 
 
 
 
 
 
 
 
 
 
 
Vessel mapping3 
X 
 
 
 
 
 
 
 
 
 
 
Assessment of central vein 
stenosis 
X 
 
 
 
 
 
 
 
 
 
 
Confirmation of eligibility 
(inclusion/exclusion criteria)4 
X 
X 
 
 
 
 
 
 
 
 
 
Surgical placement of HAV and 
documentation of any 
complications 
 
X 
 
 
 
 
 
 
 
 
 
Labs5 
X 
 
 
X 
X 
 
 
 
 
 
 
PRA / anti-HAV IgG 
X 
 
 
X 
X 
 
X 
X 
 
 
X 
Assessment of surgical site healing 
 
 
X 
X 
 
 
 
 
 
 
 
Clinical examination of access site 
and HAV 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
Documentation of problems with 
access site and HAV and 
interventions 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 

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Screening 
D -45 to D 
0 
D 0 
 
D79 
D 28 
M 2 
M 3 
M 6 
M 12 
M 18-36 at 
6M 
intervals 
 
ET10 
Assessment of HAV Patency6 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Duplex Ultrasound Examination 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
Determine suitability of HAV for 
dialysis7 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
Document removal of pre-
implantation CVC (if applicable) 
 
 
X 
X 
X 
X 
 
 
 
 
X 
Document hemodialysis / CVC use 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
Adverse Events / Events of Special 
Interest8  
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Abbreviations: D: day; M: Month; ECG: electrocardiogram; ET: early termination; PRA: panel reactive antibody; CVC: central venous catheter; IgG: Immunoglobulin G. 
1: Record all prescription medications and aspirin the subject has taken in the 7 days prior to surgery (Day 0). At all other study visits, concomitant medications as well as aspirin taken 
during the study up to Month 12 will be recorded. 
2: A complete PE will be performed at Screening, including height, weight, resting blood pressure and heart rate and temperature. Standard of care physical exams conducted prior to 
consent may be used for determination of eligibility provided they are within the screening period time window and all required data are available. Symptom-directed PEs will be 
conducted at all other study visits, as appropriate (denoted as (X)). Temperature should be obtained at all visits. 
3: If adequate vessel mapping has been undertaken within the 8 weeks prior to the start of Screening and there has been no significant change in the condition of the subject (including 
insertion of CVC) then repeat vessel mapping is at the discretion of the Principal Investigator. Vessel mapping performed by ultrasound in the clinic by the investigator is acceptable. 
4: After review by the Principal Investigator, the subject’s Screening eCRFs will be provided to the Medical Monitor for review and confirmation of eligibility prior to implantation. 
5: Labs include hematology and chemistry. Screening labs will also include INR (or PT if INR value not available) and a serum or urine pregnancy dipstick test for women of 
childbearing potential. Standard of care laboratory evaluations conducted prior to consent may be used for determination of eligibility provided they are within the screening period time 
window. 
6: Intraoperatively or immediately post-surgery and at Day 7-15, the investigator should use his/her preferred method to confirm patency and adequate flow in the HAV. At all other 
timepoints, duplex ultrasound will be used to assess patency, diameter of the lumen mid-conduit and flow rate and to monitor aneurysm development. After Month 12, a duplex 
ultrasound is to be performed at Month 24 and 36. 
7: Beginning on Day 28, the investigator may evaluate the HAV to determine if it is suitable to be used for dialysis. 
8: Only SAEs related to the screening procedures will be reported during the Screening period. All AEs will be reported from Day 0 after implantation up to the Month 12 visit. After the 
Month 12 visit up to Month 36, only the following will be reported by the investigator: 
• 
All SAEs considered related to the HAV 
• 
All Events of Special Interest. 
9: Subjects will be assessed at a study visit that can occur anytime from Day 7 to 15. 
10: Subjects withdrawn prior to the Month 36 visit will have ET assessments performed. Patients withdrawn prior to Month 12 should complete an ET that correlates with the 
procedures at Month 12. Patients withdrawn after Month 12 and prior to Month 36 should complete an ET visit that correlates with procedures post Month 12 through Month 36.