An Assessment of Humacyte's Human Acellular Vessel in Patients Needing Renal Replacement Therapy: A Comparison With ePTFE Grafts as Conduits for Hemodialysis (HUMANITY)
Phase: PHASE3
Conditions: Renal Failure, End Stage Renal Disease, Hemodialysis, Vascular Access
Sponsor: Humacyte, Inc.

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An Assessment of Humacyte’s Human Acellular Vessel in Patients 
Needing Renal Replacement Therapy: A Comparison with ePTFE 
Grafts as Conduits for Hemodialysis (HUMANITY) 
  
Medicinal Product: 
 
Human Acellular Vessel (HAV) 
Study No.: 
 
 
CLN-PRO-V006 
 
 
 
 
 
Sponsor: 
 
 
Humacyte, Inc.  
Address: 
2525 East NC Highway 54 
Durham, NC 27713 
Phone:  
 
 
1.919.313.9633 
Fax: 
 
 
 
1.919.238.1719 
 
CRO:  
 
 
CTI Clinical Trial and Consulting Services 
 
 
 
 
100 E. RiverCenter Blvd. 
Covington, KY 41011 
 
IND No.: 
 
 
15263 
EudraCT No.:  
 
2015-003261-28 
 
Date:  
 
 
08 August 2018 
Version:  
 
 
5.0  
 
 
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 national and local regulatory requirements 
 
 

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Site Principal Investigator Agreement Page for the Protocol 
Protocol Version 5.0 Dated: 08 August 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 
relevant regulatory authorities, 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 Medical Officer, Humacyte, Inc. 
Signed: 
Date: 
27Aug2018

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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 ........................................................................................................................ 11 
PROTOCOL SUMMARY ............................................................................................................................ 13 
1. 
STUDY PERSONNEL ......................................................................................................................... 25 
2. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ................................................... 28 
2.1 
END STAGE RENAL DISEASE AND ITS MANAGEMENT ....................................................................... 28 
2.1.1 Humacyte Human Acellular Vessel ......................................................................................... 29 
2.1.2 Comparator .............................................................................................................................. 29 
2.2 
SUMMARY OF HUMAN ACELLULAR VESSEL NONCLINICAL STUDIES ................................................... 29 
2.3 
SUMMARY OF HUMAN ACELLULAR VESSEL CLINICAL STUDIES ......................................................... 31 
2.3.1 Experience in Dialysis Patients ............................................................................................... 31 
2.3.2 Human Acellular Vessel Host Response and Remodeling Data ............................................. 34 
2.3.3 Experience in Peripheral Arterial Disease Patients ................................................................. 35 
2.4 
STUDY DESIGN RATIONALE ............................................................................................................ 36 
2.4.1 Study Population ..................................................................................................................... 36 
2.4.2 Comparator Expanded Polytetrafluoroethylene Grafts ........................................................... 37 
2.4.3 Rationale for Efficacy Endpoints.............................................................................................. 37 
2.5 
POTENTIAL RISKS AND BENEFITS ................................................................................................... 40 
2.5.1 Potential Risks ......................................................................................................................... 40 
2.5.2 Potential Benefits ..................................................................................................................... 41 
3. 
STUDY OBJECTIVES ........................................................................................................................ 42 
3.1 
PRIMARY OBJECTIVE ..................................................................................................................... 42 
3.2 
SECONDARY OBJECTIVES .............................................................................................................. 42 
3.2.1 Key Secondary Objectives: ..................................................................................................... 42 
3.2.2 Other Secondary Objectives: ................................................................................................... 42 
4. 
STUDY DESIGN ................................................................................................................................. 43 
4.1 
DESCRIPTION OF THE STUDY DESIGN ............................................................................................. 43 

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4.2 
STUDY ENDPOINTS ........................................................................................................................ 43 
4.2.1 Primary Endpoint ..................................................................................................................... 43 
4.2.2 Secondary Endpoints .............................................................................................................. 43 
4.2.3 Events of Special Interest ........................................................................................................ 44 
4.3 
DURATION OF STUDY PARTICIPATION ............................................................................................. 45 
5. 
STUDY POPULATION ....................................................................................................................... 46 
5.1 
DESCRIPTION OF THE STUDY POPULATION ...................................................................................... 46 
5.1.1 Inclusion Criteria ...................................................................................................................... 46 
5.1.2 Exclusion Criteria ..................................................................................................................... 47 
5.2 
RANDOMIZATION ............................................................................................................................ 48 
6. 
INVESTIGATIONAL MEDICINAL PRODUCT ................................................................................... 49 
6.1 
HUMAN ACELLULAR VESSEL ........................................................................................................... 49 
6.1.1 Product Description ................................................................................................................. 49 
6.1.2 Manufacturer of the Investigational Medicinal Product ........................................................... 49 
6.1.3 Packaging, Storage, and Labeling .......................................................................................... 49 
6.1.4 Implantation of the Humacyte Human Acellular Vessel .......................................................... 50 
6.2 
COMPARATOR GRAFTS .................................................................................................................. 50 
6.2.1 Product Description ................................................................................................................. 50 
6.2.2 Manufacturer of Comparator Grafts ........................................................................................ 50 
6.2.3 Storage .................................................................................................................................... 50 
6.2.4 Implantation of the Comparator Grafts .................................................................................... 50 
6.3 
INVESTIGATIONAL MEDICINAL PRODUCT ACCOUNTABILITY PROCEDURES ......................................... 51 
6.3.1 Human Acellular Vessel .......................................................................................................... 51 
6.3.2 Comparator Grafts ................................................................................................................... 51 
7. 
OTHER TREATMENTS AND MEDICATIONS ................................................................................... 52 
7.1 
PRIOR AND CONCOMITANT MEDICATIONS ....................................................................................... 52 
7.2 
ESSENTIAL AND RESTRICTED MEDICATIONS .................................................................................... 52 
7.2.1 Essential Medications .............................................................................................................. 52 
7.2.2 Restricted Medications ............................................................................................................ 53 
8. 
STUDY PROCEDURES / EVALUATIONS ......................................................................................... 54 
8.1 
SCREENING (BASELINE) (DAY -35 TO DAY 0) .................................................................................. 54 

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8.1.1 Informed Consent .................................................................................................................... 54 
8.1.2 Demographics.......................................................................................................................... 54 
8.1.3 Medical History ........................................................................................................................ 54 
8.1.4 Prior and Concomitant Medications ........................................................................................ 55 
8.1.5 Physical Exam, Vital Signs and Temperature ......................................................................... 55 
8.1.6 Electrocardiogram ................................................................................................................... 55 
8.1.7 Laboratory Evaluations ............................................................................................................ 55 
8.1.8 Vessel Mapping ....................................................................................................................... 56 
8.1.9 Document Reason for Not Creating a Fistula .......................................................................... 56 
8.1.10 Assessment of Central Vein Stenosis ..................................................................................... 56 
8.1.11 Review of Eligibility for Randomization ................................................................................... 56 
8.1.12 Serious Adverse Events .......................................................................................................... 56 
8.2 
RANDOMIZATION AND SURGICAL PLACEMENT OF THE HAV OR THE EPTFE GRAFT (DAY 0) .............. 56 
8.2.1 Medical History and Concomitant Medications ....................................................................... 56 
8.2.2 Symptom-directed Physical Examination, including Temperature .......................................... 56 
8.2.3 Confirmation of Eligibility and Randomization ......................................................................... 57 
8.2.4 Surgical Placement .................................................................................................................. 57 
8.2.5 Confirmation of Patency .......................................................................................................... 57 
8.2.6 Adverse Events ....................................................................................................................... 57 
8.3 
POSTOPERATIVE EVALUATION-DAY 7-15 VISIT ................................................................................ 57 
8.3.1 Concomitant Medications ........................................................................................................ 58 
8.3.2 Symptom-directed Physical Examination, including Temperature .......................................... 58 
8.3.3 Assessment of Surgical Site Healing ...................................................................................... 58 
8.3.4 Clinical Examination of Study Conduit .................................................................................... 58 
8.3.5 Document any Problems with the Access Site and Study Conduit and Interventions ............ 58 
8.3.6 Assessment of Study Conduit Patency and Flow.................................................................... 58 
8.3.7 Document Hemodialysis and Placement and/or Removal of Central Venous Catheter ......... 58 
8.3.8 Assessment of Adverse Events ............................................................................................... 59 
8.3.9 Assessment of Events of Special Interest ............................................................................... 59 
8.4 
POSTOPERATIVE EVALUATION-DAY 28 (±7D) VISIT ......................................................................... 59 
8.4.1 Concomitant Medications ........................................................................................................ 59 

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8.4.2 Symptom-directed Physical Examination, including Temperature .......................................... 59 
8.4.3 Assessment of Surgical Site Healing ...................................................................................... 60 
8.4.4 Clinical Examination of the Access Site and Study Conduit ................................................... 60 
8.4.5 Document any Problems with Access Site and Study Conduit and Interventions .................. 60 
8.4.6 Assessment of Study Conduit Patency ................................................................................... 60 
8.4.7 Duplex Ultrasound ................................................................................................................... 60 
8.4.8 Determination that the Study Conduit may be used for Dialysis ............................................. 60 
8.4.9 Document Hemodialysis and Placement and/or Removal of Central Venous Catheter ......... 61 
8.4.10 Assessment of Adverse Events ............................................................................................... 61 
8.4.11 Assessment of Events of Special Interest ............................................................................... 61 
8.4.12 Laboratory Evaluations ............................................................................................................ 61 
8.5 
POSTOPERATIVE EVALUATIONS (MONTH 2 TO MONTH 24) ............................................................... 61 
8.5.1 Evaluations and Procedures to be performed at All Study Visits from Month 2 to Month 24 . 61 
8.5.2 Evaluations and Procedures to be performed only at Specific Visits from Month 2 to Month 24
 63 
8.6 
MONTH 30 TO MONTH 60 EVALUATIONS AND PROCEDURES ............................................................ 64 
8.6.1 Evaluations and Procedures that will be performed at All Study Visits from Month 30 to Month 
60 (±1M) .................................................................................................................................. 64 
8.6.2 Evaluations and Procedures that will be performed at Only Specific Study Visits from Month 
30 to Month 60 ......................................................................................................................... 65 
8.7 
EARLY TERMINATION VISIT ............................................................................................................. 65 
8.7.1 Concomitant Medications (if prior to month 24) ....................................................................... 65 
8.7.2 Symptom-directed Physical Examination, including Temperature .......................................... 66 
8.7.3 Clinical Examination of the Access Site and Study Conduit ................................................... 66 
8.7.4 Assessment of Study Conduit Patency ................................................................................... 66 
8.7.5 Document any Problems with the Access Site and Study Conduit and Interventions, Including 
Events of Special Interest ........................................................................................................ 66 
8.7.6 Duplex Ultrasound ................................................................................................................... 66 
8.7.7 Document Hemodialysis and Placement and/or Removal of Central Venous Catheter ......... 66 
8.7.8 Assessment of Adverse Events ............................................................................................... 67 
8.7.9 Panel Reactive Antibodies (if prior to month 24) ..................................................................... 67 
8.8 
COLLECTION AND PROCESSING OF LABORATORY SAMPLES ............................................................. 67 

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8.8.1 Specimen Preparation, Handling and Shipping ....................................................................... 67 
9. 
SAFETY ASSESSMENTS AND ADVERSE EVENTS ....................................................................... 68 
9.1 
DEFINITION OF ADVERSE EVENTS ................................................................................................... 68 
9.1.1 Definition of Serious Adverse Events ...................................................................................... 69 
9.1.2 Suspected Unexpected Serious Adverse Reactions ............................................................... 69 
9.2 
CRITERIA FOR DETERMINING CAUSAL RELATIONSHIP TO THE IMP .................................................... 70 
9.3 
CRITERIA FOR DEFINING THE SEVERITY OF AN ADVERSE EVENT ...................................................... 71 
9.4 
REPORTING OF ADVERSE EVENTS .................................................................................................. 71 
9.4.1 Reporting of Serious Adverse Events ..................................................................................... 72 
9.4.2 Monitoring and Reporting of Serious Adverse Events Not Related to the Implanted Conduit 73 
9.4.3 Follow-Up of Adverse Events .................................................................................................. 73 
9.5 
REPORTING OF PREGNANCY .......................................................................................................... 73 
9.6 
DATA MONITORING COMMITTEE AND CLINICAL EVENTS COMMITTEE ................................................ 74 
9.6.1 Data Monitoring Committee ..................................................................................................... 74 
9.6.2 Clinical Events Committee ....................................................................................................... 74 
9.7 
NEW INFORMATION AFFECTING THE CONDUCT OF THE STUDY ......................................................... 75 
10. STATISTICAL CONSIDERATIONS ................................................................................................... 75 
10.1 
RANDOMIZATION ............................................................................................................................ 75 
10.2 
ANALYSIS POPULATION .................................................................................................................. 75 
10.3 
EFFICACY ANALYSIS ...................................................................................................................... 76 
10.3.1 Censoring for Time to Event Analyses .................................................................................... 76 
10.3.2 Primary Efficacy Analysis ........................................................................................................ 76 
10.3.3 Key Secondary Efficacy Analyses ........................................................................................... 77 
10.3.4 Additional Efficacy Analyses .................................................................................................... 78 
10.4 
SAFETY ANALYSIS ......................................................................................................................... 78 
10.5 
SAMPLE SIZE................................................................................................................................. 79 
11. STUDY MANAGEMENT AND DATA COLLECTION ........................................................................ 80 
11.1 
ETHICAL CONDUCT OF THE TRIAL ................................................................................................... 80 
11.2 
SUBJECT CONFIDENTIALITY ............................................................................................................ 80 
11.3 
INSTITUTIONAL REVIEW BOARD /INDEPENDENT ETHICS COMMITTEE ................................................. 80 
11.4 
SUBJECT INFORMED CONSENT ....................................................................................................... 81 

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11.5 
SUBSTANTIAL AMENDMENTS TO THE PROTOCOL ............................................................................. 82 
11.6 
STUDY INITIATION .......................................................................................................................... 82 
11.7 
STUDY MONITORING ...................................................................................................................... 82 
11.8 
CASE REPORT FORM ..................................................................................................................... 83 
11.8.1 Data Management ................................................................................................................... 83 
11.9 
VERIFICATION PROCEDURES .......................................................................................................... 83 
11.10 RETENTION OF RECORDS ............................................................................................................... 83 
11.11 PROTOCOL DEVIATIONS ................................................................................................................. 84 
11.12 INSURANCE AND INDEMNITY ........................................................................................................... 84 
11.13 AUDIT ........................................................................................................................................... 84 
12. REPORTING ....................................................................................................................................... 86 
12.1 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................................ 86 
13. RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR ............................................................ 87 
13.1 
INFORMED CONSENT ..................................................................................................................... 87 
13.2 
COMPLIANCE WITH THE PROTOCOL ................................................................................................ 87 
13.3 
MEDICAL CARE OF SUBJECTS ........................................................................................................ 88 
13.4 
SAFETY REPORTING ...................................................................................................................... 89 
14. SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL INVESTIGATION ............... 90 
15. PUBLICATION POLICY ..................................................................................................................... 91 
16. REFERENCES .................................................................................................................................... 92 
APPENDIX 1: VISIT SCHEDULE ............................................................................................................... 94 
 
 
 
List of In-text Figures 
Figure 1  
Time to Loss of Patency-Pooled Data (CLN-PRO-V001 and CLN-PRO-V003) 
Kaplan-Meier Plot-Secondary Patency ................................................................................ 33 
Figure 2  
Time to Loss of Patency-Pooled Data (CLN-PRO-V001 and CLN-PRO-V003) 
Kaplan-Meier Plot-Primary Patency ..................................................................................... 33 
Figure 3  
Images of Mid-Vessel Segment Explanted at 11-Months Post-Implant .................... 35 
 

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List of Abbreviations  
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
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 
CVC 
Central venous catheter 
D 
Day 
DHHS 
Department of Health and Human Services 
DMC 
Data Monitoring Committee 
DTH 
Delayed-type Hypersensitivity 
ECG 
Electrocardiogram 
ECM 
Extracellular Matrix 
eCRF 
Electronic case report form 
ePTFE 
Expanded polytetrafluoroethylene 
ESA 
Erythropoiesis-stimulating agent 
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  
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent ethics committee 
IgG 
Immunoglobulin G 
IMP 
Investigational medicinal product 

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List of Abbreviations  
IMPD 
Investigational medicinal product dossier 
IND 
Investigational new drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intent-to-Treat 
LMWH 
Low molecular weight heparin 
M 
Month 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
PAD 
Peripheral arterial disease 
PE 
Physical examination 
PHI 
Protected health information 
PP 
Per Protocol 
PRA 
Panel reactive antibody 
PT 
Prothrombin time 
PTFE 
Polytetrafluoroethylene 
RBC 
Red blood cell 
RRT 
Renal replacement therapy 
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 
ULN 
Upper limit of normal 
US 
United States  
WBC 
White blood cell 
 
 

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Protocol Summary 
Full Title 
An Assessment of Humacyte’s Human Acellular Vessel in Patients 
Needing Renal Replacement Therapy: A Comparison with ePTFE 
Grafts as Conduits for Hemodialysis (HUMANITY) 
Clinical Trial Phase 
Phase 3 
Sponsor  
Humacyte, Inc. 
Planned Study Sites 
Approximately 35 Sites in the US, Europe and Israel 
Sample Size 
At least 350 evaluable subjects with implanted study conduits; 175 
with Human Acellular Vessel (HAV), 175 with an expanded 
polytetrafluoroethylene (ePTFE) graft 
Expected Enrollment 
Start 
2Q2016 
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 
16 months 
Study Duration 
Each subject will be followed by study specific visits until he/she 
completes 2 years (24 months) of follow-up after implantation 
(irrespective of patency status). After 2 years, only subjects with a 
patent study conduit will be followed (while the study conduit 
remains patent) for up to 5 years (60 months) post-implantation at 
routine study visits. The expected duration of the clinical 
investigation 
is 
76 months 
(initiation 
of 
enrollment 
through 
completion of data collection). 
Study Design 
Prospective, multicenter, multinational, open-label, randomized, two-
arm, comparative study. 
Investigational 
Device/Intervention 
Description 
The Investigational Medicinal Product (IMP) is Humacyte’s HAV, 
which is a tissue-engineered vascular conduit for hemodialysis 
access. The comparators are one of the following commercially 
available 6 mm ePTFE grafts: 
• 
Gore® PROPATEN® Vascular Graft (6mm x 40cm, straight, 
standard wall, non-stretch, non-  tapered) 
 
• 
Bard® Impra® Vascular Graft (6mm x 40cm, straight, 
standard wall, non-stretch, non-  tapered) 

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Subjects will be implanted with either a HAV or an ePTFE graft in 
the forearm or upper arm using standard vascular surgical 
techniques.  
The randomization will occur during surgery and be 1:1 and stratified 
by upper arm or forearm placement based on the Principal 
Investigator’s determination of where the study conduit should be 
located. 
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 study conduit (Day 1). If low molecular weight heparin (LMWH) 
is administered post-operatively, aspirin or other antiplatelet agent 
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 compare the Secondary Patency of the HAV with that of the 
ePTFE graft when used as a conduit for hemodialysis.  
Secondary Objectives 
 
Key Secondary 
Objectives 
Efficacy 
To compare the Primary Patency of the HAV with that of the ePTFE 
graft. 
Safety 
To compare the rate of access-related infections for the HAV with 
that of the ePTFE graft. 
Other Secondary 
Objectives 
Efficacy 
1. To 
compare 
the 
rate 
of 
interventions 
needed 
to  
maintain/restore patency of the HAV with that of the ePTFE 
graft. 
2. To compare the Primary Assisted Patency of the HAV with 
that of the ePTFE graft. 
3. To describe the histopathological remodeling of samples from 
HAVs and ePTFE grafts. 
4. To compare the efficiency of dialysis with the HAV with that of 

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the ePTFE graft in a subset of subjects. 
Safety 
1. To compare the safety and tolerability of the HAV with that of 
the ePTFE graft.  
2. To compare the relative rates of true aneurysm and pseudo-
aneurysm formation. 
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) to start or maintain hemodialysis therapy. 
2. Either on hemodialysis or expected to start hemodialysis 
within 12 weeks of study conduit implantation. 
3. At least 18 years of age at Screening. 
4. Suitable 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 35 days). 
6. Other hematological and biochemical parameters within a 
range consistent with ESRD prior to Day 0 (within 35 days). 
7. Adequate liver function prior to Day 0 (within 35 days), 
defined as both of the following:  
a. ≤2x upper limit of normal (ULN) for serum bilirubin, 
aspartate 
transaminase 
(AST), 
and 
alanine 
transaminase (ALT)  
b. ≤1.5 for International Normalized Ratio (INR) or 
prothrombin time (PT) ≤ 18 seconds unless the 
subject is taking an anticoagulant at the time 
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 

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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 study conduit 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. 
6. Bleeding diathesis. 
7. Active clinically significant immune-mediated disease, not 
controlled by maintenance immunosuppression. 
a. Low dose glucocorticoid therapy (e.g. up to 10mg 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 

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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 study conduit 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 one 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 study conduit. 
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 Endpoint 
Time to loss of Secondary Patency from implantation 
• 
Defined as ‘the interval from the time of access placement 
until access abandonment’, i.e., patent with or without 
interventions. (Sidawy 2002)  
Secondary Endpoints 
 

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Key Secondary 
Endpoints 
Efficacy 
Time to loss of Primary Patency from implantation 
• 
Defined as ‘the interval from the time of access placement 
until any intervention designed to maintain or reestablish 
patency, access thrombosis or the time of measurement of 
patency’, i.e., patent without interventions (Sidawy 2002).  
Safety 
Access-related infections (CDC 2013).  
Other Secondary 
Endpoints 
Efficacy 
• 
Rate of interventions required to achieve/maintain Secondary 
Patency. 
• 
Time to loss of Primary Assisted Patency from implantation. 
o Defined as ‘the interval from the time of access 
placement until access thrombosis or the time of 
measurement of patency, including intervening 
manipulations 
(surgical 
or 
endovascular 
interventions) designed to maintain the functionality 
of patent access’ i.e., patent without an intervention 
to clear a thrombus (Sidawy 2002).  
• 
Histopathological remodeling of any study conduit (based on 
any samples collected). 
• 
The efficiency of dialysis as assessed by spKt/Vurea (obtained 
from dialysis unit for a subset of subjects). 
Safety 
• 
Frequency and severity of adverse events (AEs) 
• 
Study conduit dilatation: 
o True aneurysm formation (conduit lumen diameter  
> 9 mm) 
o Pseudo-aneurysm formation 
• 
Study conduit spontaneous rupture 
• 
Anastomotic bleeding or spontaneous rupture 
 
 

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Events of Special Interest 
Events of Special Interest related to interventions and infections will 
be evaluated and include the following:  
• 
Study conduit abandonment 
• 
Thrombosis / thrombectomy 
• 
Angioplasty or stenting 
• 
Access-related infection 
• 
Pseudo-aneurysm or true aneurysm (conduit lumen diameter 
>9 mm) formation  
• 
Study conduit spontaneous rupture 
o Iatrogenic injuries are not an Event of Special Interest 
and should be reported as an AE 
• 
Revision or ligation of the study conduit 
• 
Study conduit removal 
• 
Steal syndrome 
Data Analysis 
 
Populations 
The Intent-to-Treat (ITT) population is defined as all randomized 
subjects (based on study conduit group assignment). 
The modified Intent-to-Treat (mITT) population is defined as all 
subjects in whom a study conduit has been implanted (based on 
actual conduit implanted). 
The Per Protocol (PP) population is defined as all subjects in whom 
a study conduit has been implanted (based on actual conduit 
implanted) and in whom there were no major protocol violations. 
Primary Efficacy 
Analysis 
The primary efficacy analysis will be a non-inferiority analysis, which 
will be conducted when all subjects are at least 18 months post-
implantation. It will be conducted using the ITT population with 
confirmatory analyses in the mITT and PP populations. 
The following rules for the analysis will apply: 
• 
Subjects in whom the wrong study conduit was implanted 
(e.g., an HAV implanted in a subject randomized to an 

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ePTFE graft) will be analyzed within their randomized group 
rather than in their implanted group. 
• 
Subjects in whom no study conduit was implanted will be 
considered as if abandoned on Day 0 and included in their 
randomized group. 
The following censoring rules will apply to all ‘time to’ analyses: 
• 
Subjects who have patent study conduits at the time of 
death, kidney transplant or withdrawal will be censored at 
that timepoint.  
• 
Subjects who are lost to follow-up will be censored at their 
last visit when it was known that the study conduit was 
patent.  
• 
Subjects in whom a delayed decision is made to abandon 
the 
study 
conduit 
(e.g., 
delayed 
and 
then 
failed 
thrombectomy) will have the date of abandonment set as the 
date of the initial recognition of the thrombosis, not the date 
that a final decision was made.  
The hazard ratio (HAV relative to ePTFE) will be estimated using a 
Cox proportional hazards regression model with treatment group 
and the randomization stratification variable as factors.  Based on 
the estimated 18-month event-free rate in the ePTFE arm, the non-
inferiority margin will be determined by the hazard ratio 
corresponding to a difference of 10 percentage points.  If the lower 
limit of the two-sided 95% confidence interval for the hazard ratio is 
greater than the corresponding non-inferiority bound, then non-
inferiority will be demonstrated.   
Secondary Efficacy 
Analyses 
 
Key Secondary Analysis 
Efficacy 
If the primary efficacy analysis demonstrates non-inferiority, the 
following key secondary analyses will be completed at the same 
timepoint in the ITT population using a fixed sequence testing 
procedure to control the overall level of significance.  Thus, the 
results of a given key secondary analysis will be considered 
confirmatory only if the results of all previous tests are successful 
based on the use of a two-sided test at the alpha=0.05 level of 
significance.  However, once a non-successful result is obtained, all 
subsequent results will be considered as exploratory rather than 
confirmatory.  The key secondary analyses are the following: 
• 
Superiority analysis of the time to loss of Secondary 

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Patency; 
• 
Non-inferiority analysis of the time to loss of Primary 
Patency; 
• 
Superiority analysis of the time to loss of Primary Patency. 
The non-inferiority analysis of time to loss of Primary Patency will be 
completed using the same statistical approach and non-inferiority 
margin as specified for the primary analysis.   
The superiority analyses will be completed using the same statistical 
model as described for the corresponding non-inferiority analysis.  
The two arms will be compared using a two-sided test at the 
alpha=0.05 level of significance. 
In order to provide descriptive summary statistics that are of interest, 
point estimates and 95% confidence intervals for patency (Primary, 
Primary Assisted and Secondary) survival probabilities will be 
provided for each group at 6, 12, 18, and 24 months.  These 
estimates will be computed from Kaplan-Meier survival curves for 
each treatment group for each of the endpoints. 
Key Secondary Analysis 
Safety 
For each of the two treatment groups, the access-related infection 
rate will be computed in 2 ways: 
• 
Rate of access-related infections per 100 person-years of 
HAV/ePTFE use (i.e., censored at abandonment). 
• 
Rate of access-related infections per 100 person-years 
over the 2-year post-implantation follow-up period. 
These analyses will be based on adjudicated events using a 
standardized definition of access-related infections (CDC 2013).  
For each of the 2 definitions, the infection rates in the two arms will 
be compared using a Poisson regression model with treatment 
group and the randomization stratification variable as factors. This 
analysis will be conducted using a two-sided test at the alpha=0.05 
level of significance. 
Other Secondary 
Analysis  
Efficacy 
In the primary and key secondary analyses of Primary Patency and 
Secondary Patency, death will be treated as a censored outcome.  
These analyses will be repeated as supportive analyses with death 
treated as an event. Additionally, a time to event analysis will be 
conducted for all censored subjects and any subjects who withdraw 
for any reason. 
All secondary efficacy analyses that are superiority comparisons will 

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be carried out using two-sided tests at the alpha=0.05 level of 
significance, with no adjustment for multiplicity.  
The rates of interventions (number of interventions per 100 person-
years) in the two arms will be compared using a Poisson regression 
model with treatment group and the randomization stratification 
variable as factors. 
Secondary endpoints that are defined as time-to-event variables will 
be summarized using the Kaplan-Meier method and analyzed using 
the log-rank test.  Proportion endpoints will be analyzed using 
Pearson’s chi-square test and all other quantitative endpoints will be 
analyzed using the two-sample t-test.   
Any analysis on histopathological remodeling of any study conduit 
will be descriptive only. 
Other Secondary 
Analysis  
Safety  
All other safety data will be described only (i.e., no inferential 
statistics). 
Sample Size 
The original sample size calculation was based on the following 
assumptions: 
For the primary endpoint of time to loss of Secondary Patency, the 
assumed 12-month event-free rate in the ePTFE arm is 60%.  
Based on 1:1 randomization, an estimated 16-month enrollment 
period, and a 12-month follow-up period, a total sample size of 350 
subjects will provide:  
• 
90% power to demonstrate non-inferiority (non-inferiority 
margin=10%) if the 12-month event-free rate in the HAV arm  
is 66% 
• 
90% power to demonstrate superiority if the 12-month event-
free rate in the HAV arm  is 76% 
For the key secondary endpoint of time to loss of Primary Patency, 
the assumed 6-month event-free rate in the ePTFE arm is 50%.  
Based on 1:1 randomization, a 16-month enrollment period, and a 
12-month follow-up period, and under the assumption that the true 
6-month event-free rate in the HAV arm is 55%, a total sample size 
of 350 subjects will provide greater than 90% power to demonstrate 
non-inferiority.  If the true rate in the HAV arm is as low as 53%, 
then there will be greater than 80% power to demonstrate non-
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During the course of the study a high enrolling site (~10% of total 
subjects) early terminated all of their remaining subjects and 
withdrew from study participation. The majority of these subjects had 
not yet had an event that would contribute to the primary endpoint 
analysis.  To mitigate the potential loss of study power from this 
unexpected situation, the decision was made to extend the follow-up 
period for the primary and secondary efficacy analyses from 12 
months post-implant to 18 months post-implant. 
 
Data Monitoring 
Committee (DMC) 
A 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.  As part of 
their oversight of study conduct, the DMC will review the pattern of 
interventions and abandonments between treatment groups overall 
and by study site to assess whether the management of access 
complications is similar in the two treatment groups. Responsibilities 
of the DMC will include review of aggregate safety data from other 
studies in the HAV clinical development program. 
The DMC will consist of individuals who are not directly involved in 
the conduct of the study. A separate charter will be established that 
will describe the roles and responsibilities of the DMC.  
Clinical Events 
Committee (CEC) 
(Adjudication Process) 
A Clinical Events Committee (CEC) will be established to do the 
following: 
• 
Prospectively provide to study sites a set of clinical 
guidelines for study conduit interventions and abandonment. 
• 
Review study conduit interventions and abandonment in a 
blinded fashion to assess compliance with provided 
guidelines.   
• 
Adjudicate study conduit revisions to determine whether the 
original study conduit was still being used for dialysis.  
• 
Adjudicate access-related infections using the Centers for 
Disease Control and Prevention (CDC) definitions for 
dialysis-associated infections (CDC 2013). 
The CEC will consist of individuals who are not directly involved in 
the conduct of the study. A separate charter will be established that 
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Protocol Approval 
(Version and Date) 
 
v5.0    08 August 2018 
 
 

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1. STUDY PERSONNEL 
An updated 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, the 
CRO or the sites. 
 
CRO Project Manager (United States) 
Mackenzie Pater, PhD 
CTI Clinical Trial and Consulting Services 
100 E RiverCenter Blvd.Covington, KY 41011 
E-mail:  
 
mpater@ctifacts.com 
Office Phone:  
1.513.619.5514 
Mobile Phone:  
1.513.904.7805 
Fax: 
 
 
1.513.598.6909 
 
CRO Project Manager (Europe and Israel) 
Adenike Igoh 
CTI Clinical Trial and Consulting Services UK 
Regus House Highbridge Oxford Road 
UB81HR Uxbridge, UK 
E-mail:  
 
aigoh@ctifacts.com 
Office Phone:  
0044 7825 705 029 
 
 
 
 
 
 

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Serious Adverse Event (SAE) Reporting (For ALL SAE reports 24 hours/7 days a week) 
CTI Safety 
CTI Clinical Trial and Consulting Services 
100 E RiverCenter Blvd. 
Covington, KY 41011 
E-mail:  
 
CTIsafety@ctifacts.com 
 
 
Phone:  
 
1.877.755.0742 
 
 
eFax:   
 
Country-specific fax numbers will be provided in the study manual  
 
 
Note: Medical Monitors for the study are available for time-sensitive discussions for the US and 
for Europe/Israel. 
Medical Monitor (United States) 
Rob Gordon, MD, FACS 
CTI Clinical Trial and Consulting Services 
100 E RiverCenter Blvd. 
Covington, KY 41011 
E-mail:  
 
rgordon@ctifacts.com 
Office Phone:  
1.513.619.4781 
Mobile Phone:  
1.404.843.8010 
Fax: 
 
 
1.513.521.4646 
 
Medical Monitor (Europe and Israel) 
Achim Nutzenberger, MD, PhD 
CTI Clinical Trial and Consulting Services Europe GmbH 
Schillerstrasse 1/15 
89077 Ulm, Germany 
E-mail:  
 
anutzenberger@ctifacts.com 
Office Phone:  
+49 (0) 731 4000 0 
Mobile Phone:  
+49 (0) 170 4123 969 
Fax: 
 
 
+49 (0) 731 4000 84 29 
 

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Humacyte Chief Executive Officer/Chief Medical Officer 
Jeffrey H. Lawson, MD, PhD 
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 
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 (RRT). 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 six 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 

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associated with a high potential for infection and shorter patient survival (Bray 2012, Thompson 
2007).  
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 Comparator 
The comparator in this study will be a 6 mm diameter expanded polytetrafluoroethylene 
(ePTFE) graft. The grafts to be used in the comparator arm will be one of the following (at the 
discretion of the Principal Investigator at each site): 
• 
Gore® PROPATEN® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, 
non-tapered) 
• 
Bard® Impra® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, non-
tapered) 
2.2 Summary of Human Acellular Vessel 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–

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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 
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 

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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  
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 (DTH) immune response. No DTH reactions were observed in any animals.  
Biocompatibility assessments of the HAV ECM were conducted in accordance with 
internationally-recognized (International Organization for Standardization [ISO]) 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 Human Acellular Vessel Clinical Studies 
There are three ongoing Phase 2 trials with the HAV; two studies in dialysis that have enrolled a 
total of 60 subjects and one in peripheral arterial disease (PAD) that has enrolled 20 subjects. 
More information on the clinical profile of the HAV in these ongoing studies is provided in the 
Investigator Brochure. 
2.3.1 Experience in Dialysis Patients 
Two clinical studies are ongoing in subjects with ESRD, one in Poland (CLN-PRO-V001) and 
one in the United States (US; CLN-PRO-V003); both recruited subjects not suitable for creation 
of an autologous AVF. Most had experienced previous vascular access procedures, in many 
cases multiple attempts including both AV fistulae and synthetic grafts.   
Initially, the HAV was not used for hemodialysis cannulation before 8 weeks; an amendment to 
the Polish study protocol (after 30 subjects) shortened that restriction to 4 weeks without any 
problems. The primary objectives of these two studies are to evaluate safety and efficacy 

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(Primary and Secondary Patency) at 6 months. Secondary objectives include measurement of a 
panel of reactive antibodies (PRA) response plus a 2 year evaluation of patency and an 
assessment of the need for interventions to maintain/restore patency. 
All subjects (n=60) have now completed at least 12 months since implantation (or had a 
censoring event). Together these two trials provide an average of 17.7 months (range 12 to >24 
months) of follow-up in 60 subjects with thousands of hemodialysis sessions. Overall there are 
81.6 years of follow-up across the 60 subjects. The mean number of previous access-surgeries 
was 4 (range 1-9). 
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 CVC.  
Regular ultrasound surveillance has demonstrated an absence of true aneurysms or dilatation 
and flow rates through the HAV more than sufficient to allow for effective dialysis. While there 
have been a few pseudo-aneurysms, there have been no true dilatations nor aneurysms or 
significant changes in vessel diameter indicative of weakening or structural degeneration.  
Across the two studies, the product has generally been well tolerated and blood chemistry, 
hematology and coagulation data are not indicative of any HAV-associated toxicity.  
Immunogenic response to the HAV material has not been observed as demonstrated by a 
general lack of HAV-related change in PRA levels (Class I or II). Three subjects had elevations 
in their PRA levels: all 3 subjects had experienced one or more renal transplant failures; one 
subject recently; one subject developed septic shock about a month before the elevated value; 
and the third subject, who was severely debilitated with a decubitus ulcer, died approximately a 
month after HAV abandonment.   
Immunoglobulin G (IgG) titers increased in 5 subjects; in 4 cases the IgG titer increased and 
then decreased while the HAV remained functional with no clinical evidence of an inflammatory 
response; in one case the IgG titer increase occurred in a subject who maintained Primary 
Patency.  
Adverse events (AE) related to the HAV / access site (excluding thrombotic events) were few; 
there have been only three access-site infections, of which only one required removal of part of 
the HAV. There have been:  
• 
1 transplant (known to be functioning well at 12 months post-transplant) 
• 
4 deaths during follow-up and 2 deaths after abandonment; none of the deaths were 
considered related to the presence of the HAV 
Across the two studies, Secondary Patency was 97% at 6 months, 89% at 12 months and 81% 
at 18 months (Figure 1); Primary Patency was 62% at 6 months and 28% at 12 months and 
21% at 18 months (Figure 2). 

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Figure 1  
Time to Loss of Patency-Pooled Data (CLN-PRO-V001 and CLN-PRO-V003) 
Kaplan-Meier Plot-Secondary Patency 
 
Subjects at risk shown for the following key timepoints: Day 30, Day 90, Day 180, Day 270, Day 360, Day 540, i.e., Month 1, 3, 6, 9, 
12, 18. 
Subjects who discontinued early, died or were transplanted with the graft still patent, were censored at that timepoint. 
Plot calculated 08 May 2015. 
 
Figure 2  
Time to Loss of Patency-Pooled Data (CLN-PRO-V001 and CLN-PRO-V003) 
Kaplan-Meier Plot-Primary Patency 
 
Subjects at risk shown for the following key timepoints: Day 30, Day 90, Day 180, Day 270, Day 360, Day 540, i.e., Month 1, 3, 6, 9, 
12, 18. 
Subjects who discontinued early, died or were transplanted with the graft still patent, were censored at that timepoint. 
Plot calculated 08 May 2015. 

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2.3.2 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 eight cases. The 
analysis (mostly of a section close to the venous anastomosis) included assessments of:  
• 
Cellular infiltration of histotypic, inflammatory and immunological populations. 
• 
Extracellular remodeling processes, including neo-synthesis and reorganization of ECM 
components that typically occur in native blood vessels. 
In 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 3). In one case, an explanted specimen was tested for suture 
retention strength at the time of explant and exhibited a substantial increase over the pre-
implant level. 
 

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Figure 3  
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. 
2.3.3 Experience in Peripheral Arterial Disease Patients 
The safety and efficacy of HAV is currently being evaluated in a single group, uncontrolled, 
multicenter study. Eligible subjects required a femoro-popliteal bypass graft for the management 
of PAD. The patency of the graft after implantation is confirmed by intraoperative angiography or 

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ultrasound and subjects are followed out to 24 months. Twenty subjects have been enrolled; 19 
have completed >6 months follow-up and 10 have completed ≥1 year; the mean follow-up is 11 
months.  
One subject died 19 days after HAV implantation, the death was considered unrelated to the 
HAV; five subjects have developed a thrombosis of the HAV. 
2.4 Study Design Rationale 
2.4.1 Study Population 
The study is designed to recruit a broad range of ESRD patients in whom a clinical decision has 
been made to implant a ‘graft’ to provide vascular access for hemodialysis. Exclusion criteria 
have been restricted to those situations where use of an HAV or an ePTFE graft is likely to be 
inappropriate or to pose a potential risk to the study subject.  
1. The trial is limited to adults because we do not believe that the diameter (6 mm) of the 
HAV is appropriate for children with smaller veins, especially if an anastomosis is placed 
distally in the arm to preserve vascular territory for future vascular access surgery. In 
addition, because the HAV does not stretch and it is unknown if it can extend to longer 
lengths after implantation, there could be a concern in children who are still growing. 
2. Study subjects should be either on hemodialysis, or anticipated to start dialysis within 12 
weeks of conduit implantation. This is to ensure that all subjects experience the regular 
needle insertions associated with hemodialysis and thus allowing us to evaluate in a 
comparative manner the integrity of the HAV in an appropriate clinical setting. 
3. Subjects with documented bleeding or clotting problems are excluded because of 
general concerns with regard to these medical conditions in a trial related to the surgical 
placement of a vascular access, not because of investigational product-related 
concerns. 
4. Subjects are excluded if they have insufficient arterial inflow or venous outflow, or any 
type of aberrant vascular anatomy that would preclude appropriate positioning of the 
HAV or the ePTFE graft.   
5. Subjects are excluded if, in the opinion of the Principal Investigator, the subject has a life 
expectancy of less than a year. This will ensure that there is a significant opportunity for 
long-term follow-up to provide robust safety information. 

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2.4.2 Comparator Expanded Polytetrafluoroethylene Grafts 
Currently, ePTFE is the most commonly implanted synthetic vascular graft material used for 
hemodialysis access.   There is a wide range of commercially available ePTFE grafts.  Because 
this trial will be conducted internationally (approximately 50% of subjects will be recruited in the 
United States [US] and 50% recruited in Europe / Israel), and because surgeon (Principal 
Investigator) preferences vary, the comparator arm will allow the individual surgeon to select 
from two of the most commonly used grafts: 
• 
Gore® PROPATEN® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, 
non-tapered) 
 
• 
Bard® Impra® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, non-
tapered) 
Both of these ePTFE grafts are approved for use in the US and are CE marked (i.e., are 
approved for use) in Europe and Israel. It is expected that the data will be pooled and that there 
will be no marked differences in performance between the selected ePTFE grafts (Allemang 
2014, Zea 2016). 
2.4.3 Rationale for Efficacy Endpoints 
2.4.3.1 Patency as the Endpoint of Interest 
Efficacy in the setting of vascular access in hemodialysis patients is usually focused on the 
usability of the conduit (patency), and on the interventions needed to maintain patency over 
time. Patency may be primary or secondary (Sidawy 2002). Primary Patency allows no 
interventions; Secondary Patency allows multiple interventions. To fully understand the utility of 
the HAV relative to commonly used commercially available ePTFE grafts, it is important to 
assess both Primary and Secondary Patency as well as the number and types of interventions 
used to maintain patency. 
In this clinical setting, efficacy is usually analyzed by a comparison of survival curves (Kaplan-
Meier Plots) – time to loss of patency, with, typically, presentation of the percent patency at 
fixed timepoints (usually at 6, 12, 18 and 24 months after implantation) (Dixon 2009, Huber 
2003, Dember 2008, Shemesh 2015).  
The biological evolution of the HAV as it is populated with cells from the subject is critical to 
understanding the potential advantages of the HAV, such as fewer access-related infections 
and longer sustained patency. However, because this evolution takes time, it is likely that early 
events (i.e., early thrombosis) will not be modulated significantly by the host cells that migrate 
into the HAV. Instead, the inherent biological properties of the HAV are more likely to translate 
into longer term patency – best described by Secondary Patency, which is very influenced by 
development of intimal hyperplasia.  Furthermore, Secondary Patency (i.e., a lack of 

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abandonment) is a better measure of the need for a replacement conduit and protection from 
unnecessary utilization of anatomical sites for potential future access placement. Access 
placement should always start as distally as possible, ideally at the wrist and then move more 
proximally. Once a particular location has been used and failed it is virtually impossible to place 
an access more distally since the outflow vein will almost always have been compromised. 
Thus, in patients who have already had one or more accesses in the upper limbs the available 
sites become limited. It is therefore worth maintaining an existing access as long as possible - 
even if this requires multiple interventions – rather than to abandon that access site and move 
on to a new site (National Kidney Foundation 2006).  
2.4.3.2 Drivers of Graft Failure 
The natural history of an implanted dialysis graft is not well described; it is likely that the causes 
of graft failure vary over the time from graft placement – though in all cases the final failure is 
thrombosis: 
1. Very early failures are likely related to surgical technique leading to thrombosis (e.g., 
twisting of the implant), immediate failure (e.g., dehiscence at an anastomosis), or 
thrombosis occurring because of inherent thrombogenicity of the graft material.   
2. Later thromboses are most likely related to a stenosis, either within the graft itself or, 
more often, associated with the development of intimal hyperplasia either at the venous 
anastomosis, where high blood flow creates zones of high shear stress, or in the 
proximal vein. 
3. Other factors contributing to the development of later thromboses include repeated graft 
punctures needed to achieve dialysis, with the associated blood flow turbulence and 
mechanical graft damage and pseudoaneurysms. 
4. There are also non-graft related causes including post-dialysis hypotension, 
compression of the access following decannulation, and others usually associated with 
problems in the draining venous system (e.g., stenosis).   
5. Other factors that may cause graft failure are infections and inappropriate dilatation. 
Support for these differential drivers of thrombosis comes from a recently published study that 
compared the patency of standard PTFE grafts with Propaten grafts (heparin bonded) 
(Shemesh 2015). In that study, time to first thrombosis (loss of Primary Patency) was superior 
for Propaten early (up to 6 months), but not later (12 months) suggesting that the bonded 
heparin was able to reduce early thromboses that were likely unrelated to the inherent 
properties of the graft material, but that heparin did not offer benefit when thromboses were 
more likely to be related to stenoses (intimal hyperplasia). However, in two recent retrospective 
studies comparing non-heparin bound ePTFE grafts to heparin bound ePTFE grafts, neither 

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Allemang, nor Zea revealed improvement in patency with heparin bound grafts in the dialysis 
access clinical setting (Allemang 2014, Zea 2016). 
2.4.3.3 Impact of the Biology of the Human Acellular Vessel on Patency 
The HAV is a unique biological product - it is not a synthetic graft; it has inherent biological 
properties that Humacyte believes may significantly differentiate it from synthetic grafts.  
Furthermore, Humacyte believes that those differences are more likely to manifest themselves 
in the longer term, when remodeling has progressed and host cells have populated the matrix.  
It is of interest that in a single anecdotal case, there is evidence of ‘healing’ of cannulation tracts 
with host cell infiltration into cannulation sites.   
The HAV is cultured from adult 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. The HAV is comprised of the ECM proteins 
that are secreted by the vascular smooth muscle cells during culture. These proteins include 
collagen types I and III, but also the glycoproteins and proteoglycans that are typically found in 
normal human arteries.   
When host cells populate the HAV after implantation, they encounter these vascular ECM 
proteins. It is possible that the responses of these populating cells in the HAV may be different 
from the responses of host cells that infiltrate PTFE grafts. Pre-clinical work in primates (Dahl 
2011) and in pigs (Quint 2011) showed that the propensity for intimal hyperplasia in 
decellularized HAVs was less than is typically seen in vein and PTFE grafts in pigs and 
baboons, respectively.  
These pre-clinical studies point to a potential for the HAV to develop less intimal hyperplasia 
than synthetic vascular grafts. This is an important consideration since intimal hyperplasia is a 
common cause of graft failure and abandonment. Early data from the ongoing Phase 2 trials 
support the potential for longer conduit survival. The observed Secondary Patency with HAV 
appears to be superior to that seen in historical trials with PTFE grafts; 89% at 1 year vs 50% to 
60% for synthetic grafts. 
2.4.3.4 Choice of Secondary Patency as the Primary Endpoint 
For the reasons described above, the study’s analysis strategy is designed to examine those 
aspects of efficacy that primarily would be driven by the inherent biological aspects of the HAV. 
For these reasons, the primary objective of the study is the comparison between treatment 
groups of Secondary Patency, with Primary Patency as a key secondary objective. 
A further consideration for selecting Secondary Patency as the primary efficacy endpoint 
(compared with the often use of Primary Patency) is that this is a randomized and controlled 
study.  In this setting, the impact of physician decisions on interventions will be balanced across 
the two arms (not the case in historical studies which were typically single-arm assessments of 

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conduit performance).  The prospective development by the Clinical Events Committee of 
clinical guidelines on management decisions will encourage physician balanced decisions about 
interventions to maintain patency across the two arms of the study (see 2.4.3.5 below). 
2.4.3.5 Controlling against Bias 
This is an open-label, comparative study. It is not possible to blind the investigators or study 
subjects. Study endpoints (see Section 4.2) will be determined by the clinical decisions of the 
investigators (except as noted below for study conduit revisions and access-related infections).  
To reduce the potential for bias the Clinical Events Committee (CEC) (as described in Section 
9.6.2) will: 
• 
Prospectively provide to study sites a set of clinical guidelines for study conduit 
interventions and abandonment. 
• 
Review study conduit interventions and abandonment in a blinded fashion to assess 
compliance with these guidelines.   
o Assessments by the CEC of the appropriateness of interventions will be provided 
to the DMC by the CEC Coordinator (an employee of the CRO with no other 
study-related responsibilities). As part of their oversight of study conduct, the 
DMC will review the pattern of interventions and abandonments between 
treatment groups overall and by study site to assess whether the management of 
access complications is similar in the two treatment groups. 
• 
Adjudicate study conduit revisions to determine whether the original study conduit was 
still being used for dialysis.  
• 
Adjudicate access-related infections using the Centers for Disease Control and 
Prevention (CDC) definitions for dialysis-associated infections (CDC 2013).  
The outcome of these adjudications (i.e., those involving study conduit revisions and access-
related infections) will be used as endpoints in the trial rather than the investigator 
determinations.  All other study endpoints will be based on the clinical decisions of the 
investigators. 
Additionally, across-study cumulative event rates overall and by study arm will not be available 
to staff involved in the management of the study or study subject care. 
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 and the ePTFE graft 
may include, but are not limited to, the following: 

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• 
Aneurysm or pseudo-aneurysm formation 
• 
Conduit rupture 
• 
Bleeding and hematoma formation at the surgical site or the dialysis puncture sites 
• 
Thrombosis/occlusion of the conduit or host vessels 
• 
Stenosis of the conduit or its anastomoses 
• 
Infection of the conduit, 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 was one aneurysmal dilatation of the HAV 
reported in the Phase 2 experience.  The superficial site of implantation of the conduit 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 compare the Secondary Patency of the HAV with that of the ePTFE graft when used as a 
conduit for hemodialysis. 
3.2 Secondary Objectives 
3.2.1 Key Secondary Objectives: 
 
Efficacy 
To compare the Primary Patency of the HAV with that of the ePTFE graft. 
Safety 
To compare the rate of access-related infections for the HAV with that of the ePTFE graft. 
3.2.2 Other Secondary Objectives: 
Efficacy 
1. To compare the rate of interventions needed to maintain/restore patency of the HAV with 
that of the ePTFE graft. 
2. To compare the Primary Assisted Patency of the HAV with that of the ePTFE graft. 
3. To describe the histopathological remodeling of samples from HAV and ePTFE grafts. 
4. To compare the efficiency of dialysis with the HAV with that of the ePTFE graft in a 
subset of subjects. 
Safety 
1. To compare the safety and tolerability of the HAV with that of the ePTFE. 
2. To compare the relative rates of true aneurysm and pseudo-aneurysm formation. 

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4. STUDY DESIGN 
4.1 Description of the Study Design 
This is a Phase 3, prospective, multicenter, multinational, open-label, randomized, two-arm, 
comparative study. Subjects who sign informed consent would undergo study-specific screening 
assessments within 35 days from the day of informed consent.  
On the day of surgery (Day 0), subjects could still be undergoing screening assessments, such 
as confirmation of inclusion/exclusion criteria, to determine their eligibility before they are 
randomized in the study. Eligible study subjects will be randomized to receive either a HAV or 
one of two commercially available ePTFE grafts and followed to 24 months post-implantation at 
routine study visits regardless of patency status. After 24 months, subjects with a patent study 
conduit will be followed (while the study conduit remains patent) for up to 5 years (60 months) 
post-implantation at routine study visits. 
4.2 Study Endpoints 
4.2.1 Primary Endpoint 
Time to loss of Secondary Patency from implantation 
• 
Defined as ‘the interval from the time of access placement until access 
abandonment’, i.e., patent with or without interventions (Sidawy 2002).  
• 
“Abandonment” defined as no remaining segment of the study conduit is 
incorporated into the vascular access circuit used for dialysis (conversely, if some 
portion of the study conduit is still being used for dialysis it is not considered 
abandoned). 
4.2.2 Secondary Endpoints 
4.2.2.1 Key Secondary Endpoints: 
Efficacy 
Time to loss of Primary Patency from implantation 
• 
Defined as ‘the interval from the time of access placement until any intervention 
designed to maintain or reestablish patency, access thrombosis or the measurement 
of patency’, i.e., patent without interventions (Sidawy 2002).  
Safety 

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Access-related infections (CDC 2013)  
 
4.2.2.2 Other Secondary Endpoints: 
Efficacy 
1. Rate of interventions required to achieve/maintain Secondary Patency 
2. Time to loss of Primary Assisted Patency from implantation 
a. Defined as ‘the interval from the time of access placement until access 
thrombosis or the time of measurement of patency, including intervening 
manipulations (surgical or endovascular interventions) designed to maintain 
the functionality of patent access’ i.e., patent without an intervention to clear a 
thrombus (Sidawy 2002). 
3. Histopathological remodeling of any study conduit (based on any samples collected). 
4. The efficiency of dialysis as assessed by spKt/Vurea (obtained from dialysis unit for a 
subset of subjects). 
Safety 
1. Frequency and severity of AEs 
2. Study conduit dilatation: 
a. True aneurysm formation (conduit lumen diameter > 9 mm) 
b. Pseudo-aneurysm formation 
3. Study conduit spontaneous rupture 
4. Anastomotic bleeding or spontaneous rupture 
4.2.3 Events of Special Interest 
Events of Special Interest related to interventions and infections will be evaluated and include 
the following:  
• 
Study conduit abandonment 
• 
Thrombosis / thrombectomy 
• 
Angioplasty or stenting 
• 
Access-related infection 

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• 
Pseudo-aneurysm or true aneurysm (conduit lumen diameter >9 mm ) formation  
• 
Study conduit spontaneous rupture 
o Iatrogenic injuries are not an Event of Special Interest and should be reported as 
an AE 
• 
Revision or ligation of the study conduit 
• 
Study conduit removal 
• 
Steal syndrome 
4.3 Duration of Study Participation 
Each subject will be followed at study specific visits until he/she has completed 24 months of 
follow-up after implantation (irrespective of patency status). After 24 months, subjects with a 
patent study conduit will be followed (while the study conduit remains patent) for up to 5 years 
(60 months) post-implantation at routine study visits. 
The expected duration of the clinical investigation is 76 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) to start or maintain hemodialysis therapy. 
2. Either on hemodialysis or expected to start hemodialysis within 12 weeks of study 
conduit implantation. 
3. At least 18 years of age at Screening. 
4. Suitable 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 35 
days). 
6. Other hematological and biochemical parameters within a range consistent with 
ESRD prior to Day 0 (within 35 days). 
7. Adequate liver function prior to Day 0 (within 35 days), defined as both of the 
following:  
a. ≤2x upper limit of normal (ULN) for serum bilirubin, aspartate transaminase 
(AST), and alanine transaminase (ALT)  
b. ≤1.5 for International Normalized Ratio (INR) or prothrombin time (PT) ≤ 18 
seconds unless the subject is taking an anticoagulant at the time 
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 

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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. 
 
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 study conduit 
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. 
6. Bleeding diathesis. 
7. Active clinically significant immune-mediated disease, not controlled by maintenance 
immunosuppression. 
a. Low dose glucocorticoid therapy (e.g. up to 10mg 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. 

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9. Venous outflow from study conduit 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 one 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 study conduit. 
14. Previous enrollment in this study or any other study with HAV. 
15. Employees of Humacyte and employees or relatives of the investigator. 
5.2 Randomization  
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 electronic case report form (eCRF) for eligible subjects will then be reviewed and eligibility 
confirmed by the Medical Monitor prior to randomization.  
Study site personnel will randomize the subject to either HAV or ePTFE during surgery (i.e., 
after the surgical site [upper- vs fore-arm] has been selected and after confirmation that the 
subject is not a candidate for creation of an autologous AV fistula). Randomization may only 
occur once the arterial and venous exposures have been completed with confirmation of 
adequate arterial inflow and venous outflow.  The randomization schema will ensure that 
subjects will be assigned on a 1:1 basis to the HAV or ePTFE arms of the study. The 
randomization will be stratified by the upper arm or forearm placement based on the 
Investigator’s determination of where the study conduit should be located.  
 
 

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6. INVESTIGATIONAL MEDICINAL PRODUCT 
Additional information on the manufacturing process and testing of HAV is provided in the 
Investigator Brochure.  
6.1 Human Acellular Vessel 
6.1.1 Product Description 
The IMP is Humacyte’s human acellular vessel (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 is 6 mm in diameter and approximately 42 cm in length. 
The product is supplied on a silicone mandrel immersed in sterile, phosphate buffered saline in 
a sealed and labeled plastic container. 
6.1.2 Manufacturer of the Investigational Medicinal Product 
The HAV is manufactured by: 
 
AlloSource 
 
6278 S. Troy Circle 
 
Centennial, CO 80111 USA 
 
Traceability of the HAV during and after the clinical investigation will be achieved by the 
assignment of lot numbers. A unique identifying lot number will be assigned to each vessel. 
6.1.3 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. 
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. 

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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 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 for details).  
6.2 Comparator Grafts 
6.2.1 Product Description 
The comparator in this study is one of the following commercially available 6 mm ePTFE grafts: 
• 
Gore® PROPATEN® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, 
non-tapered) 
 
• 
Bard® Impra® Vascular Graft (6mm x 40cm, straight, standard wall, non-stretch, non-
tapered) 
6.2.2 Manufacturer of Comparator Grafts 
The comparator grafts are manufactured by: 
• 
W.L. Gore & Associates, Inc. 
Flagstaff, AZ 86004 USA 
• 
Bard Peripheral Vascular, Inc. 
Tempe, AZ 85281 USA 
Traceability of the comparator grafts during and after the clinical investigation will be achieved 
by tracking lot numbers for each graft. 
6.2.3 Storage  
The storage of the comparator grafts should follow the approved Product Information for the 
respective products. 
6.2.4 Implantation of the Comparator Grafts 
Implantation of the comparator grafts will follow standard vascular surgical techniques described 
in the approved Instructions for Use for the respective products. 

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6.3 Investigational Medicinal Product Accountability Procedures 
6.3.1 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 Receipt Form. Once signed, the IMP 
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, at which time the 
original will be retrieved by Humacyte or its authorized designee and a copy kept at the site. 
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. 
6.3.2 Comparator Grafts 
The comparator grafts will be provided by the study sites through commercially available stock, 
or by Humacyte via a third party distributor. The lot numbers for each graft used during the 
study will be documented. 
 
 

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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 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 medications taken during the study, only medication name, indication for use and 
start and stop dates will be recorded in the eCRF. 
7.2 Essential and Restricted Medications  
7.2.1 Essential Medications 
All subjects should receive both antibiotic and antithrombotic therapy in conjunction with HAV 
and ePTFE graft implantation: 

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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.  
Antithrombotic prophylaxis: 
Intra-operative heparin: Use, 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 study conduit (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, 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 -35 to Day 0) 
The screening period time window is currently specified as a maximum of 35 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. Subjects 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 Institutional Review Board (IRB) / Independent Ethics 
Committee (IEC) approved consent form. The informed consent will cover: 
• 
Agreement to participate in the trial for the full 5 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 study conduit 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).  

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8.1.4 Prior and Concomitant Medications 
Record all prescription medications and aspirin that the subject is taking or has taken within 7 
days prior to surgery 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 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. 
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, ALT, AST, alkaline phosphatase, glucose (non-
fasting). 
• 
INR or PT (if INR value is not available) 
• 
PRA 
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. 

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8.1.8 Vessel Mapping 
Vessel mapping will be performed during Screening to determine whether the vessels in the 
operative limb are suitable for conduit 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 Document Reason for Not Creating a Fistula 
The Principal Investigator will document the reasons why an AV graft will be implanted rather 
than an AV fistula created. 
8.1.10 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 study conduit is planned is 
identified / suspected, it must be corrected before randomization. 
8.1.11 Review of Eligibility for Randomization 
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 randomization. 
8.1.12 Serious Adverse Events  
Only serious adverse events (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 Randomization and Surgical Placement of the HAV or the ePTFE 
Graft (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 Eligibility and Randomization 
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 randomization.  
Study site personnel will randomize the subject to either HAV or ePTFE during surgery (i.e., 
after the surgical site [upper- vs fore-arm] has been selected and after confirmation that the 
subject is not a candidate for creation of an autologous AV fistula). Randomization may occur 
once the arterial and venous exposures have been completed with confirmation of adequate 
arterial inflow and venous outflow. The randomization schema will ensure that subjects will be 
equally assigned on a 1:1 basis to the HAV or ePTFE arms of the study. The randomization will 
be stratified by upper arm or forearm placement based on the Principal Investigator’s 
determination of where the study conduit should be located.  
8.2.4 Surgical Placement 
Document the surgical procedure for implantation, including the location of the study conduit, 
and any complications immediately postoperatively. Indicate whether subject remained in the 
hospital the night after surgery; if so, indicate 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 study conduit will be confirmed intraoperatively or 
immediately post-surgery by the investigator’s preferred method (eg. Physical exam, Doppler, 
ultrasound, etc) (to be documented).  
8.2.6 Adverse Events  
All adverse events (AEs) will be collected beginning on Day 0 after implantation up to 2 years 
post-implantation (Month 24). The subject will be asked general questions about his/her health 
and for any conduit 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: 

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8.3.1 Concomitant Medications 
Record all concomitant prescription medications and aspirin use in the eCRF. 
8.3.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) and obtain subject’s temperature. 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. 
8.3.3 Assessment of Surgical Site Healing 
A clinical examination of the surgical site should be conducted and the findings documented in 
the eCRF. 
8.3.4 Clinical Examination of Study Conduit 
A clinical examination of the access site and study conduit will be performed at all postoperative 
study visits. 
8.3.5 Document any Problems with the Access Site and Study Conduit and 
Interventions 
Document any problems and interventions with the access site and study conduit including 
infections and the occurrence of thrombosis. Any procedures performed or treatments, including 
reasons for the procedures and dates of hospitalization, will be documented in the eCRF. 
8.3.6 Assessment of Study Conduit Patency and Flow 
The patency of the study conduit and adequacy of flow will be assessed by the investigator 
using the investigator’s preferred method (eg. palpation, stethoscope auscultation, Doppler, 
ultrasound, etc). 
8.3.7 Document Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Document if the subject underwent hemodialysis since the last study visit, including frequency. 
Document if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit. Of particular interest is whether an alternate route for dialysis (CVC, peritoneal) is used 
and for how long. 

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8.3.8 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any conduit or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.3.9 Assessment of Events of Special Interest 
Events of Special Interest are defined in Section 4.2.3, and the subject should be assessed at 
each postoperative study visit for these events. For each of these events detailed surgical notes 
(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 9.1.1), whether or not causally related to the 
IMP, the event must be reported by the investigator to CTI 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 5 years post-implantation.  This information will 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/ePTFE 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 
Record all concomitant prescription medications and aspirin use in the eCRF. 
8.4.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) and obtain 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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8.4.3 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 Study Conduit 
A clinical examination of the access site and study conduit will be performed at all postoperative 
study visits. 
8.4.5 Document any Problems with Access Site and Study Conduit and 
Interventions 
Document any problems and interventions with the access site and study conduit including 
infections and the occurrence of thrombosis. Any procedures performed or treatments, including 
reasons for the procedures and dates of hospitalization, will be documented in the eCRF. 
8.4.6 Assessment of Study Conduit Patency 
The patency of the study conduit 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 study conduit 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 study conduit should be visualized with particular 
attention paid to any increase in diameter of the conduit that might indicate aneurysm formation. 
The methodology will be described in the study manual. 
8.4.8 Determination that the Study Conduit may be used for Dialysis 
Beginning on Day 28 post-implantation (±7 days), the surgeon should evaluate the study 
conduit to determine if it is suitable to be used for dialysis.  Such suitability needs to recorded in 
the eCRF and transmitted to the dialysis center caring for that subject with guidance that 
cannulation of the study conduit for dialysis should not start before 28 days post-implantation. 
If the study conduit is deemed not ready for use, either the subject should be brought back for a 
repeat assessment, or an intervention arranged. 

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8.4.9 Document Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Document if the subject underwent hemodialysis since the last study visit, including frequency. 
Document if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit. Of particular interest is whether an alternate route for dialysis (CVC, peritoneal) is used 
and for how long. 
8.4.10 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any conduit 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 4.2.3. 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, ALT, AST, alkaline phosphatase, glucose (non-fasting). 
8.5 Postoperative Evaluations (Month 2 to Month 24) 
8.5.1 Evaluations and Procedures to be performed at All Study Visits from 
Month 2 to Month 24 
The following assessments will be performed at the Month 2 (±7D), 3 (±14D), 6 (±14D), 9 (±1M), 
12 (±1M), 18 (±1M) and 24 (±1M) visits: 
8.5.1.1 Concomitant Medications 
All concomitant prescription medications and aspirin taken during the study up to Month 24 will 
be recorded in the eCRF. 

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8.5.1.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) and obtain 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. 
8.5.1.3 Clinical Examination of the Access Site and Study Conduit 
A clinical examination of the access site and study conduit will be performed at all postoperative 
study visits. 
8.5.1.4 Assessment of Study Conduit Patency 
The patency of the study conduit and adequacy of flow will be assessed by the investigator 
using the investigator’s preferred method (eg. Physical exam [ie. palpation, stethoscope 
auscultation], Doppler exam, ultrasound imaging, etc). 
 
8.5.1.5 Document any Problems with the Access Site and Study Conduit and 
Interventions, Including Events of Special Interest 
Document any problems and interventions with the access site and study conduit including 
infections and the occurrence of thrombosis. Any procedures performed or treatments, including 
reasons for the procedures and dates of hospitalization, will be documented in the eCRF. 
Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 4.2.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9. If the study conduit is abandoned, the reason for abandonment will 
be documented in the eCRF. 
8.5.1.6 Determination that the Study Conduit may be used for Dialysis 
The surgeon should evaluate the study conduit to determine if it is suitable to be used for 
dialysis.  Such suitability needs to recorded in the eCRF and transmitted to the dialysis center 
caring for that subject with guidance that cannulation of the study conduit for dialysis should not 
start before 28 days post-implantation. 
If the study conduit is deemed not ready for use, either the subject should be brought back for a 
repeat assessment, or an intervention arranged. 

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8.5.1.7 Document Hemodialysis and Placement and/or Removal of CVC 
Document if the subject underwent hemodialysis since the last study visit, including frequency. 
Document if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit. Of particular interest is whether an alternate route for dialysis (CVC, peritoneal) is used 
and for how long. 
8.5.1.8 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any conduit 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 24 
8.5.2.1 Duplex Ultrasound: Month 2, 3, 6, 12, 18 and 24 
A duplex ultrasound will be performed to assess study conduit 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 study conduit should be visualized with particular 
attention paid to any increase in diameter of the conduit that might indicate aneurysm formation. 
8.5.2.2 Document Removal of CVC that was in place Pre-randomization: Month 2 and 3 
Record the date and reason for removal of the CVC that was in place pre-randomization, if 
applicable. 
8.5.2.3 Additional Data from Dialysis Unit: Month 3, 6, 12, 18 and 24 
For a subset of subjects, the CRO will obtain, via data transfers from dialysis organizations, the 
following data obtained at a time closest but prior to the study visit (these data will be obtained 
from labs drawn at the discretion of the dialysis unit; where feasible and appropriate, these data 
will be obtained prior to study conduit implantation, too): 
• 
spKt/Vurea (to enable assessment of dialysis efficiency) 
• 
Hemoglobin  
• 
Erythropoiesis-stimulating agent (ESA) used and dose 
• 
HbA1c (last value prior to study conduit implantation only) 

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8.5.2.4 PRA: Month 6, 12, 18 and 24 
PRA samples will be drawn at Month 6, 12, 18, and 24.  PRA samples should also be drawn 
prior to transplantation for any subjects who receive a transplant during the study. 
8.5.2.5 Laboratory Data: Month 6, 12, 18 and 24 
At Month 6, 12, 18 and 24, 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, ALT, AST, alkaline phosphatase, glucose (non-fasting) 
8.6 Month 30 to Month 60 Evaluations and Procedures 
8.6.1 Evaluations and Procedures that will be performed at All Study Visits 
from Month 30 to Month 60 (±1M) 
8.6.1.1 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed PE (if needed) and obtain subject’s temperature. 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. 
8.6.1.2 Clinical Examination of Access Site and Study Conduit 
A clinical examination of the access site and study conduit will be performed at all postoperative 
study visits. 
8.6.1.3 Assessment of Study Conduit Patency 
The patency of the study conduit 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). 
8.6.1.4 Document any Problems with the Access Site and Study Conduit and 
Interventions, Including Events of Special Interest 
Document any problems and interventions with the access site and study conduit including 
infections and the occurrence of thrombosis. Any procedures performed or treatments, including 
reasons for the procedures and dates of hospitalization, will be documented in the eCRF. 

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Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 4.2.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9. If the study conduit is abandoned, the reason for abandonment will 
be documented in the eCRF. 
8.6.1.5 Determination that the Conduit may be used for Dialysis 
The surgeon should evaluate the study conduit to determine if it is suitable to be used for 
dialysis.  Such suitability needs to recorded in the eCRF and transmitted to the dialysis center 
caring for that subject with guidance that cannulation of the study conduit for dialysis should not 
start before 28 days post-implantation. 
If the study conduit is deemed not ready for use, either the subject should be brought back for a 
repeat assessment, or an intervention arranged. 
8.6.1.6 Document Hemodialysis and Placement and/or Removal of CVC 
Document if the subject underwent hemodialysis since the last study visit, including frequency. 
Document if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit. Of particular interest is whether an alternate route for dialysis (CVC, peritoneal) is used 
and for how long. 
8.6.2 Evaluations and Procedures that will be performed at Only Specific 
Study Visits from Month 30 to Month 60 
8.6.2.1 Duplex Ultrasound: Month 36, 48 and 60 
A duplex ultrasound will be performed to assess study conduit 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 study conduit should be visualized with particular 
attention paid to any increase in diameter of the conduit that might indicate aneurysm formation. 
8.7 Early Termination Visit 
If a subject discontinues from the study before the Month 60 visit, then every effort should be 
made to perform the following early termination (ET) visit assessments.  Subjects withdrawn 
prior to Month 24 should complete an ET visit that correlates with the procedures at Month 24.  
Subjects withdrawn after Month 24 and prior to Month 60 should complete an ET visit that 
correlates with procedures post Month 24 through Month 60. 
8.7.1 Concomitant Medications (if prior to month 24) 
Record any changes to the subject’s prescription medications and aspirin use in eCRF. 

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8.7.2 Symptom-directed Physical Examination, including Temperature 
Perform a symptom-directed (if needed) and obtain subject’s temperature. 
8.7.3 Clinical Examination of the Access Site and Study Conduit 
A clinical examination of the access site and study conduit will be performed. 
8.7.4 Assessment of Study Conduit Patency 
The patency of the study conduit 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 Document any Problems with the Access Site and Study Conduit and 
Interventions, Including Events of Special Interest 
Document any problems and interventions with the access site and study conduit including 
infections and the occurrence of thrombosis. Any procedures performed or treatments, including 
reasons for the procedures and dates of hospitalization, will be documented in the eCRF. 
Subjects should be assessed for the occurrence of Events of Special Interest as defined in 
Section 4.2.3. Detailed information about each of these events will be recorded in the eCRF as 
described in Section 8.3.9.  If the study conduit 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 study conduit 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 study conduit should be visualized with particular 
attention paid to any increase in diameter of the conduit that might indicate aneurysm formation. 
8.7.7 Document Hemodialysis and Placement and/or Removal of Central 
Venous Catheter 
Document if the subject underwent hemodialysis since the last study visit, including frequency. 
Document if the subject has a CVC in place or if the subject had a CVC in place since the last 
visit. Of particular interest is whether an alternate route for dialysis (CVC, peritoneal) is used 
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8.7.8 Assessment of Adverse Events 
The subject will be asked general questions about his/her health and for any conduit or dialysis 
problems since the previous visit. See Section 9 for information regarding AE collection and 
data handling. 
8.7.9 Panel Reactive Antibodies (if prior to month 24) 
Obtain a blood sample to measure PRA level. 
8.8 Collection and Processing of Laboratory Samples 
Blood collection will occur at the specified time points using a standard venipuncture technique. 
Blood collection tubes must be used in the order specified below to avoid cross-contamination 
of additives between tubes. The order of draw is as follows: 
FIRST:  
Chemistry labs will be drawn first. On visits when safety labs and PRA are 
performed (Screening and Month 6, 12, 18 and 24), draw two tubes (no additives) – the first is 
for chemistry, the second is for PRA. On Day 28, draw one tube (no additives) for chemistry. 
[See Section 8.8.1 for processing of this sample] 
SECOND: 
Draw one hematology tube - (EDTA tube)  
Hematology and chemistry samples will be analyzed at the study site’s local laboratory. PRA 
samples will be analyzed at a central laboratory. 
8.8.1 Specimen Preparation, Handling and Shipping 
Chemistry and Hematology Tubes – transport to the appropriate local clinical laboratory 
according to institutional procedures.  
Second Non-Additive Tube for PRA testing – Allow sufficient time for the blood to clot and then 
centrifuge the tube to separate the serum from clotted material (if needed, based on tube used). 
Transfer at least 0.5 mL of serum into a pre-labeled screw cap vial (provided by Humacyte) for 
PRA testing. Transfer this vial to a secure, monitored freezer (≤ -20°C). 
Shipment of PRA vials: Samples for PRA analysis will be shipped to Humacyte (in batches, if 
possible) using appropriate cooling material in an insulated container that will maintain the 
frozen state of the samples for the shipping period. Further details will be provided in the Study 
Manual. 
 
 
 

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9. SAFETY ASSESSMENTS AND ADVERSE EVENTS 
The safety of the HAV and the ePTFE graft will be assessed in terms of the following: 
• 
Anastomotic bleeding or spontaneous rupture 
• 
Conduit dilatation (aneurysm formation [conduit lumen diameter >9 mm] or pseudo-
aneurysm) 
• 
Conduit spontaneous rupture 
• 
Conduit infection 
• 
Need for conduit removal 
• 
Access-related bleeding requiring intervention 
• 
Other AEs 
• 
Laboratory parameters (clinical chemistry and hematology) 
• 
Increase from baseline in PRA 
 
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.  
It should be noted that from a technical regulatory perspective the HAV is a biologic medicinal 
product while the ePTFE graft is a device.  For the purposes of this study and to allow for better 
cross-treatment arm comparisons of safety, and given that the IMP is a biologic drug, all events 
will be reported as if both arms were drugs. 
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 one of the following criteria: 
• 
Induces clinical signs or symptoms 
• 
Requires active intervention 

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• 
Requires interruption or discontinuation of the IMP 
• 
The abnormality or test result is clinically significant in the opinion of the investigator. 
9.1.1 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 
ability to conduct normal life functions. 
• 
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 study conduit will not be considered an 
SAE. However, prolongation of the initial hospitalization due to an AE will be considered a SAE. 
9.1.2 Suspected Unexpected Serious Adverse Reactions  
A suspected unexpected serious adverse reaction (SUSAR) is any adverse drug reaction (ADR) 
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 

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"unexpected" if it is not listed in the Investigator Brochure or is not listed at the specificity or 
severity that has been observed. 
9.2 Criteria for Determining Causal Relationship to the IMP 
The criteria for determining the causal relationship of an AE with the IMP is presented in the 
table below. 
Causal 
Relationship to the 
IMP 
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 IMP 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 
IMP). 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 
IMP) 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 IMP or, another 
cause is obvious and in which there is sufficient information that the 
etiology of the event is not related to the IMP. 
 

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9.3 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. 
9.4 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 -35 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 2 years post-implantation (Month 24 visit) or ET visit, 
whichever occurs earlier, all AEs will be reported. 
 
 

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During the long-term follow-up period from 2 years to 5 years post-implantation, only the 
following will be reported by the investigator: 
• 
All SAEs considered related to the HAV 
• 
All Events of Special Interest.   
9.4.1 Reporting of Serious Adverse Events 
Any SAE which occurs during the course of this study (as defined in Section 9.1.1), whether or 
not causally related to the IMP, must be reported by the investigator to CTI Safety immediately 
(no later than 24 hours after learning of its occurrence).  
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 in the respective region (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 IMP. 
Humacyte or Humacyte's designee will submit expedited safety reports to the regulatory 
agencies as necessary, and will inform the investigators of such regulatory reports. Investigators 
must submit safety reports as required by their IRB/IEC within timelines set by regional 

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regulations. Documentation of the submission to and receipt by the IRB/IEC of expedited safety 
reports should be retained by the site. 
9.4.2 Monitoring and Reporting of Serious Adverse Events Not Related to 
the Implanted Conduit 
Patients with ESRD have significant co-morbidities and typically experience many SAEs related 
to those co-morbidities that are not related to the implanted dialysis conduit.  Investigators will 
be asked, as part of their reporting, to identify whether a particular SAE is study conduit-related.   
For those events identified as not being related to the study conduit, Humacyte will monitor 
these events throughout the course of the study for any difference in frequency to confirm that 
there is not a link to the implanted conduit. Occurrences of non-conduit related SAEs will be 
excluded from expedited reporting to the applicable regulatory authorities and to IRB/IECs. If 
aggregate analysis of these events indicates they occur more frequently with the IMP, an 
expedited safety report may be submitted. 
Regardless of whether the SAE is considered study conduit related or not, the Principal 
Investigator’s reporting obligations for events that meet the definition of a SAE as described in 
Section 9.1.1 do not change.   
9.4.3 Follow-Up of Adverse Events 
If any AEs are present when a subject completes 2 years 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. 
9.5 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 CTI 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 
CTI 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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9.6 Data Monitoring Committee and Clinical Events Committee  
9.6.1 Data Monitoring Committee 
A 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.  
As part of their oversight of study conduct, the DMC will review the pattern of interventions and 
abandonments between treatment groups overall and by study site to assess whether the 
management of access complications is similar in the two treatment groups. The DMC will 
consist of individuals who are not directly involved in the conduct of the study. 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. 
9.6.2  Clinical Events Committee 
A Clinical Events Committee (CEC) will be established to do the following: 
• 
Prospectively provide to study sites a set of clinical guidelines for study conduit 
interventions and abandonment. 
• 
Review study conduit interventions and abandonment in a blinded fashion to assess 
compliance with provided guidelines.  Assessments by the CEC will be provided to the 
DMC by the CEC Coordinator (an employee of the CRO with no other study-related 
responsibilities). 
• 
Adjudicate study conduit revisions to determine whether the original study conduit was 
still being used for dialysis.  
• 
Adjudicate access-related infections using the Centers for Disease Control and 
Prevention (CDC) definitions for dialysis-associated infections (CDC 2013). 
The outcome of these adjudications (i.e., those involving study conduit revisions and access-
related infections) will be used as endpoints in the trial rather than the investigator 
determinations.  All other study endpoints will be based on the clinical decisions of the 
investigators. 
The CEC will consist of individuals who are not directly involved in the conduct of the study. A 
separate charter will be established that will describe the roles and responsibilities of the CEC. 

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9.7 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. Investigators should inform the IRB/IEC of such information when needed. 
10. STATISTICAL CONSIDERATIONS 
This is a prospective, multicenter, multinational, open-label, randomized, two-arm, comparative 
study to compare the efficacy and safety of Humacyte’s HAV with that of a ePTFE graft in 
subjects with ESRD. The primary objective of this study is to compare the Secondary Patency of 
the HAV and ePTFE grafts in these subjects. The key secondary objectives of this study are to 
compare the Primary Patency of the HAV and ePTFE grafts, and to compare the rate of access-
related infections for the HAV and ePTFE grafts. 
Additional details of data handling and planned statistics are provided in the Statistical Analysis 
Plan. 
10.1 Randomization 
Subjects will be randomized 1:1 to receive an HAV or an ePTFE graft. Randomization will be 
stratified by arm placement location (upper arm versus forearm placement) based on the 
Investigator’s determination of where the study conduit should be located. Randomization by 
country will be used to ensure there is approximately the same count of subjects in each 
treatment group across each country. Prior to surgery the subject’s eligibility will be reviewed by 
the Investigator and confirmed by the Medical Monitor.  During surgery the Investigator will 
determine the implantation site (forearm versus upper arm) and confirm that the subject is not a 
candidate for creation of an autologous AV fistula.  Randomization may occur once the arterial 
and venous exposures have been completed with confirmation of adequate arterial inflow and 
venous outflow. 
10.2 Analysis Population 
Efficacy 
The primary analysis will be in the Intent-to-Treat (ITT) population with confirmatory analyses in 
the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. 
The ITT population is defined as all randomized subjects (based on study conduit group 
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The mITT population is defined as all subjects in whom a study conduit has been implanted 
(based on actual conduit implanted). 
The PP population is defined as all subjects in whom a study conduit has been implanted 
(based on actual conduit implanted) and in whom there were no major protocol deviations. 
Safety  
The safety analysis will be conducted using the safety population, which is defined as all 
subjects who receive study treatment, with the subject’s treatment group based on the treatment 
that was received. 
10.3 Efficacy Analysis 
10.3.1 Censoring for Time to Event Analyses 
• 
Subjects who have patent study conduits at the time of death, kidney transplant or 
withdrawal will be censored at that timepoint (additional efficacy analyses will consider 
death as an event-see Section 10.3.4).  
• 
Subjects who are lost to follow-up will be censored at their last visit when it was known 
that the study conduit was patent.  
• 
Subjects in whom a delayed decision is made to abandon the study conduit (e.g., 
delayed and then failed thrombectomy) will have the date of abandonment set as the 
date of the initial recognition of the thrombosis, not the date that a final decision was 
made.  
These censoring rules will apply to all ‘time to’ analyses.   
10.3.2 Primary Efficacy Analysis 
The primary efficacy endpoint is the time to loss of Secondary Patency.  
Study endpoints (see Section 4.2) will be determined by the clinical decisions of the 
investigators except for the following events that will be adjudicated by the CEC: 
• 
Study conduit revisions to determine whether the original study conduit was still being 
used for dialysis.  
• 
Access-related infections using the Centers for Disease Control and Prevention (CDC) 
definitions for dialysis-associated infections (CDC 2013). 

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The outcome of these adjudications will be used as endpoints in the trial rather than the 
investigator determinations.   
The primary analysis will be a non-inferiority analysis, which will be conducted when all subjects 
are at least 18 months post-implantation.  
The primary analysis will be in the ITT population with confirmatory analyses in the mITT and 
PP populations. 
The following rules will apply to the ITT population:  
• 
Subjects in whom the wrong study conduit was implanted (e.g., an HAV implanted in 
a subject randomized to an ePTFE graft) will be analyzed within their randomized 
group rather than in their ‘implanted’ group. 
• 
Subjects in whom no study conduit was implanted will be considered as if 
abandoned on Day 0 and included in their randomized group.  
The hazard ratio (HAV relative to ePTFE) will be estimated using a Cox proportional hazards 
regression model with treatment group and the randomization stratification variable as factors.  
Based on the estimated 18-month event-free rate in the ePTFE arm, the non-inferiority margin 
will be determined by the hazard ratio corresponding to a difference of 10 percentage points. If 
the lower limit of the two-sided 95% confidence interval for the hazard ratio is greater than the 
corresponding non-inferiority bound, then non-inferiority will be demonstrated. 
10.3.3 Key Secondary Efficacy Analyses 
If the primary efficacy analysis demonstrates non-inferiority, the following key secondary 
analyses will be completed at the same timepoint in the ITT population using a fixed sequence 
testing procedure to control the overall level of significance. Thus, the results of a given key 
secondary analysis will be considered confirmatory only if the results of all previous tests are 
successful based on the use of a two-sided test at the alpha=0.05 level of significance. 
However, once a non-successful result is obtained, all subsequent results will be considered as 
exploratory rather than confirmatory.  The key secondary analyses are as follows: 
• 
Superiority analysis of the time to loss of Secondary Patency 
• 
Non-inferiority analysis of the time to loss of Primary Patency 
• 
Superiority analysis of the time to loss of Primary Patency 
The non-inferiority analysis of time to loss of Primary Patency will be completed using the same 
statistical approach and non-inferiority margin as specified for the primary analysis.   

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The superiority analyses will be completed using the same statistical model as described for the 
corresponding non-inferiority analysis.  The two arms will be compared using a two-sided test at 
the alpha=0.05 level of significance. 
10.3.4 Additional Efficacy Analyses 
In order to provide descriptive summary statistics that are of interest, point estimates and 95% 
confidence intervals for patency (Primary, Primary Assisted and Secondary) survival 
probabilities will be provided for each group at 6, 12, 18, and 24 months.  These estimates will 
be computed from Kaplan-Meier survival curves for each treatment group for each of the 
endpoints. 
In the primary and key secondary analyses of Primary Patency and Secondary Patency, death 
will be treated as a censored outcome.  These analyses will be repeated as supportive analyses 
with death treated as an event. Additionally, a time to event analysis will be conducted for all 
censored subjects and any subjects who withdraw for any reason. 
The rates of interventions (number of interventions per 100 person-years) in the two arms will 
be compared using a Poisson regression model with treatment group and the randomization 
stratification variable as factors. 
Secondary endpoints that are defined as time-to-event variables will be summarized using the 
Kaplan-Meier method and analyzed using the log-rank test. Proportion endpoints will be 
analyzed using Pearson’s chi-square test and all other quantitative endpoints will be analyzed 
using the two-sample t-test.   
All secondary analyses that are superiority comparisons will be carried out using two-sided tests 
at the alpha=0.05 level of significance, with no adjustment for multiplicity.  
Any analysis of histopathological remodeling on any study conduit will be descriptive only. 
10.4 Safety Analysis 
The safety analysis will be conducted in the safety population.   
For each of the two treatment groups, the access-related infection rate will be computed in 2 
ways:   
• 
Rate of access-related infections per 100 person-years of HAV/ePTFE use (i.e., 
censored at abandonment) 
• 
Rate of access-related infections per 100 person-years over the 2-year post-implantation 
follow-up period   

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These analyses will be based on adjudicated events using a standardized definition of access-
related infections (CDC 2013).  
For each of the 2 definitions, the infection rates in the two arms will be compared using a 
Poisson regression model with treatment group and the randomization stratification variable as 
factors.  This analysis will be conducted using a two-sided test at the alpha=0.05 level of 
significance. 
All other safety data will be described only (i.e., no inferential statistics). 
For the analysis of study conduit dilatation and aneurysm formation, descriptive data will be 
presented by Visit.  In addition, the number of study conduits showing true aneurysm formation 
(internal conduit diameter >9 mm) or pseudo-aneurysm will be reported.  
10.5 Sample Size 
The original sample size calculation was based on the following assumptions: 
For the primary endpoint of time to loss of Secondary Patency, the assumed 12-month event-
free rates in the ePTFE arm is 60%. Based on 1:1 randomization, a 16-month enrollment period, 
and a 12-month follow-up period, a total sample size of 350 subjects will provide:  
• 
90% power to demonstrate non-inferiority (non-inferiority margin=10%) if the 12-month 
event-free rate in the HAV arm  is 66% 
• 
90% power to demonstrate superiority if the 12-month event-free rate in the HAV arm is 
76% 
For the key secondary endpoint of time to loss of Primary Patency, the assumed 6-month event-
free rate in the ePTFE arm is 50%.  Based on 1:1 randomization, a 16-month enrollment period, 
and a 12-month follow-up period, and under the assumption that the true 6-month event-free 
rate in the HAV arm is 55%, a total sample size of 350 subjects will provide greater than 90% 
power to demonstrate non-inferiority.  If the true rate in the HAV arm is as low as 53%, then 
there will be greater than 80% power to demonstrate non-inferiority. 
During the course of the study a high enrolling site (~10% of total subjects) early terminated all 
of their remaining subjects and withdrew from study participation. The majority of these subjects 
had not yet had an event that would contribute to the primary endpoint analysis.  To mitigate the 
potential loss of study power from this unexpected situation, the decision was made to extend 
the follow-up period for the primary and secondary efficacy analyses from 12 months post-
implant to 18 months post-implant. 
 
 

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11. STUDY MANAGEMENT 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, 
International Conference on Harmonization [ICH] E6). 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. 
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 IRB/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 (PHI) obtained 
during a research study complies with the federal and/or regional legislation related to the 
privacy and protection of personal information. 
11.3   Institutional Review Board /Independent Ethics Committee  
Institutional Review Boards (IRBs)/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 IRB/IEC to his/her IRB/IEC for review 
and approval.  A copy of the written approval must be provided to the CRO. The documentation 
should clearly mention the approval/favorable opinion of the protocol, the subject informed 
consent form, and subject recruitment materials (if applicable), including respective version 

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dates.  The written approval and a list of current membership, or Department of Health and 
Human Services (DHHS) Assurance Number or letter from the IEC/IRB stating that the 
membership list is on file, must be obtained from the IRBs/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 IRB/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 IRB/IEC. This 
includes notification to the IRB/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 IRB/IEC, and submission of final study reports and 
summaries to the IRB/IEC. 
11.4   Subject Informed Consent 
Subjects must sign and date an IRB/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 study conduits 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, ICH E6 
guideline (GCP), and in accordance with any local regulations. The investigator (or designee 
such as the CRO) is responsible for the preparation, content, and IRB/IEC approval of the 
informed consent document. The consent form must be approved by the site’s IRB/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 IRB/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 IRB/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 (MedDRA). 
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 two 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 two 
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 (IMPD) 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 
IRB/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 
IRB/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/IRB 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 12-month endpoint, a clinical study report 
will be generated, including a summary of all available data, statistical measures, tabulated 
results, graphical results and interpretations. This report will be submitted to regulatory 
authorities in a timely manner. Addenda to the report will be generated and submitted to 
regulatory authorities that will include data up to 24 months, and then up to 60 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, IRB/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 IRB/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 9.1.1 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, IRB/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 IRB/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 IRB/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 (ICMJE) 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. 
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. 
Roy-Chaudhury P, Kelly BS, Miller MA, et al. Venous neointimal hyperplasia in 
polytetrafluoroethylene dialysis grafts. Kidney Int 2001;59:2325-34. 

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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 -35 to D 0 
D 0 
D 7-1511 
D 28 
M 2 
M 3 
M 6 
M 9 
M 12 
M 18 
M 24 
M 30-60 at 
6M intervals 
 
ET12 
Visit Window 
-- 
-- 
-- 
±7 D 
±7 D 
±14 D 
±14 D 
±1 M 
±1 M 
±1 M 
±1 M 
±1 M 
 
-- 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Physical exam and temperature2 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
 
(X) 
ECG (12-lead) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vessel mapping3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Document reason for not 
creating a fistula 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessment of central vein 
stenosis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of eligibility 
(inclusion/exclusion criteria)4 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization during surgery 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical 
placement 
of 
study 
conduit and documentation of 
any complications 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Labs5 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
 
 
 
PRA6 
X 
 
 
 
 
 
X 
 
X 
X 
X 
 
 
X 
Assessment of surgical site 
healing 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Clinical examination of access 
site and study conduit 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Documentation of problems with 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 

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Abbreviations: D: day; M: Month; ECG: electrocardiogram; ET: early termination: PRA: panel reactive antibody; CVC: central venous catheter. 
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 24 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 randomization. 
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. PRA samples should be drawn prior to transplantation for any subjects who receive a transplant during the study prior to Month 24. 
access site and study conduit 
and interventions 
Assessment of Study Conduit 
Patency 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Duplex Ultrasound Examination 7 
 
 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
Determine suitability of study 
conduit for dialysis8 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Document removal of pre-
randomization CVC (if 
applicable) 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Visits associated with transfer of 
dialysis efficiency  data & 
additional lab data from dialysis 
organizations to CRO (in subset 
of subjects)9 – no site action 
needed 
 
 
 
 
 
X 
X 
 
X 
X 
X 
 
 
 
Document hemodialysis / CVC 
use 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Adverse Events / Events of 
Special Interest10  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 

Humacyte, Inc 
                                                       Confidential 
 
 
      08 August 2018 
Study No. CLN-PRO-V006 
 
 
 
 
 Version 5.0 
 
 
 
96 of 96 
7: 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 study conduit. At all 
other timepoints (except Month 9), duplex ultrasound will be used to assess patency, diameter of the lumen mid-conduit and flow rate and to monitor aneurysm development. After 
Month 24, a duplex ultrasound is to be performed at Month 36, 48 and 60. 
8: Beginning on Day 28, the investigator may evaluate the study conduit to determine if it is suitable to be used for dialysis. 
9: Dialysis efficiency (spKt/Vurea) and additional lab data (hemoglobin, ESA used and dose and HbA1c) will be obtained from dialysis organizations for a subset of subjects via data 
transfers to the CRO.  These data will be obtained from labs drawn at the discretion of the dialysis unit; where feasible and appropriate, these data will be obtained prior to study 
conduit implantation, too (HbA1c will be obtained pre-implantation only, when possible).  No site involvement is required in this process. 
10: 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 24 visit. After 
the Month 24 visit up to Month 60, only the following will be reported by the investigator: 
• 
All SAEs considered related to the HAV 
• 
All Events of Special Interest. 
11: Subjects will be assessed at a study visit that can occur anytime from Day 7 to 15. 
12: Subjects withdrawn prior to the Month 60 visit will have ET assessments performed.  Subjects withdrawn prior to Month 24 should complete an ET visit that correlates with the 
procedures at Month 24.  Subjects withdrawn after Month 24 and prior to Month 60 should complete an ET visit that correlates with procedures post Month 24 through Month 60.