A Prospective, Multicenter, Open-Label, First-in-Human Phase 1/2 Study With Two Cohorts to Evaluate the Safety, Tolerability, and Efficacy of Various Doses of VC-01™ Combination Product in Subjects With Type 1 Diabetes Mellitus
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Sponsor: ViaCyte

VC01-101 
 
A Prospective, Multicenter, Open-Label, First-in-Human  
Phase 1/2 Study with Two Cohorts to Evaluate the  
Safety, Tolerability, and Efficacy of Various Doses of  
VC-01TM Combination Product in Subjects with  
Type 1 Diabetes Mellitus 
 
 
Study Protocol 
 
Final Version 2.4 
 
 
01-Mar-2016 
 
 
ViaCyte Inc. 
 
 
NCT02239354 
 
 
 

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Final Version 2.4 (Site-Specific Amendment) 
Protocol #VC01-101 
 
01 MARCH 2016 
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A PROSPECTIVE, MULTICENTER, OPEN-LABEL,  
FIRST-IN-HUMAN PHASE 1/2 STUDY WITH TWO 
COHORTS TO EVALUATE THE SAFETY, 
TOLERABILITY, AND EFFICACY OF VARIOUS DOSES 
OF VC-01™ COMBINATION PRODUCT IN SUBJECTS 
WITH TYPE 1 DIABETES MELLITUS 
 
 
 
Protocol Number  VC01-101 
Compound PEC-01™ cells with Encaptra® drug delivery 
system [together known as VC-01 
combination product] 
US IND #  016048 
Study Phase  1/2 
Sponsor Name and Address ViaCyte Inc., 3550 General Atomics Ct., San 
Diego, CA 92121 
Version Number  2.4 (Site-Specific Amendment) 
 
 
 
 

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Protocol #VC01-101 
 
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TABLE OF CONTENTS 
PROTOCOL SUMMARY ...............................................................................................................8 
LIST OF ABBREVIATIONS ........................................................................................................12 
1. 
INTRODUCTION ......................................................................................................14 
1.1. 
Background Information and Scientific Rationale .....................................................14 
1.2. 
Investigational Product ...............................................................................................15 
1.3. 
Nonclinical Information ..............................................................................................16 
1.3.1. 
Evaluation of Safety of PEC-01 Cells ........................................................................16 
1.3.2. 
Nonclinical Evaluation of Safety of the Encaptra Drug Delivery System 
Component ..................................................................................................................16 
1.3.3. 
Nonclinical Evaluation of Safety and Efficacy of VC-01 ..........................................17 
1.4. 
Potential Clinical Risks and Benefits .........................................................................18 
1.4.1. 
Potential Risks ............................................................................................................18 
1.4.2. 
Known Potential Benefits ...........................................................................................20 
2. 
OBJECTIVES AND ENDPOINTS ............................................................................20 
2.1. 
Study Objectives .........................................................................................................21 
2.2. 
Study Endpoint Measures ...........................................................................................21 
2.3. 
Primary Endpoint Measures .......................................................................................22 
2.4. 
Secondary Endpoint Measures ...................................................................................22 
2.5. 
Exploratory Endpoint Measures .................................................................................23 
3. 
STUDY DESIGN .......................................................................................................23 
3.1. 
Cohort 1 ......................................................................................................................23 
3.2. 
Cohort 2 ......................................................................................................................24 
4. 
STUDY POPULATION .............................................................................................26 
4.1. 
Number of Patients and Sites ......................................................................................26 
4.2. 
Entry Criteria ..............................................................................................................26 
4.2.1. 
Inclusion Criteria ........................................................................................................26 
4.2.2. 
Exclusion Criteria .......................................................................................................27 
4.3. 
Strategies for Recruitment and Retention ...................................................................29 
4.4. 
Treatment Assignment Procedures .............................................................................29 

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4.4.1. 
Enrollment Procedures ................................................................................................30 
4.5. 
Lifestyle Guidelines ....................................................................................................30 
4.5.1. 
Dietary Restrictions ....................................................................................................30 
4.5.2. 
Exogenous Insulin Treatment and Administration .....................................................30 
4.5.3. 
Physical Activity .........................................................................................................31 
4.5.4. 
Alcohol, Caffeine and Tobacco ..................................................................................31 
4.5.5. 
Contraception ..............................................................................................................31 
4.5.5.1. 
Women – Non-childbearing Potential ........................................................................32 
4.5.6. 
Other Restrictions .......................................................................................................32 
5. 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT ...............................32 
5.1. 
Study Product Description ..........................................................................................32 
5.1.1. 
Acquisition ..................................................................................................................32 
5.1.2. 
Manufacturing, Formulation, Packaging, and Labeling .............................................32 
5.1.3. 
Product Storage and Stability .....................................................................................33 
5.1.4. 
Transport of Investigational Product to Site ...............................................................34 
5.2. 
Dosage, Preparation, and Administration of Product .................................................34 
5.3. 
Modification of Study Intervention for a Subject .......................................................34 
5.4. 
Accountability Procedures ..........................................................................................35 
5.5. 
Assessment of Investigational Product Subject Compliance ......................................35 
5.6. 
Concomitant Medications/Treatments ........................................................................35 
6. 
STUDY SCHEDULE .................................................................................................35 
6.1. 
Screening Visit 1 (Week -4 to Week -3) ....................................................................36 
6.2. 
Screening Visit 2 (Week -3 to Week -2) ....................................................................37 
6.3. 
Enrollment / Implantation Visit 3 (Day 1) ..................................................................38 
6.4. 
Visit 4 (Day 2) ............................................................................................................39 
6.5. 
Visit 5 (Day 5) ............................................................................................................40 
6.6. 
Visit 6 (Week 2) ..........................................................................................................40 
6.7. 
Visit 7 (Week 4) ..........................................................................................................41 
6.8. 
Visit 8 (Week 8) ..........................................................................................................42 
6.9. 
Visit 9 (Week 12) ........................................................................................................42 
6.10. 
Visits 10 and 13 (Weeks 16 and 39) ...........................................................................43 

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6.11. 
Visit 11 (Week 20) ......................................................................................................44 
6.12. 
Visits 12 and 14 (Weeks 26 and 52) ...........................................................................45 
6.13. 
Visits 15 and 17 (Weeks 65 and 91) ...........................................................................46 
6.14. 
Visit 16 (Week 78) ......................................................................................................46 
6.15. 
Visit 18 (Week 104/Early Termination) .....................................................................47 
6.16. 
Follow-up Visit 19 (Week 105) ..................................................................................48 
6.17. 
Unplanned Visits ........................................................................................................49 
7. 
STUDY ASSESSMENTS ..........................................................................................49 
7.1. 
Clinical Evaluations ....................................................................................................50 
7.1.1. 
Physical Examination .................................................................................................50 
7.1.2. 
Body Weight ...............................................................................................................50 
7.1.3. 
12-lead ECG ...............................................................................................................50 
7.1.4. 
Vitals:  Sitting Blood Pressure, Pulse Rate, and Temperature ...................................51 
7.2. 
Mixed Meal Tolerance Test (MMTT) ........................................................................51 
7.3. 
Implantation Procedure ...............................................................................................52 
7.4. 
Photographs of Implantation and Explantation Sites ..................................................54 
7.5. 
Video of Implantation and Explantation Procedures ..................................................54 
7.6. 
Ultrasound Monitoring ...............................................................................................54 
7.7. 
Explantation of VC-01-20™ or Comparator Sentinel Units .......................................55 
7.8. 
Explantation of VC-01-250™ Units ............................................................................56 
7.9. 
Histological Assessment of Sentinel Units and VC-01-250™ Units ..........................57 
7.10. 
Blood Glucose Monitoring .........................................................................................57 
7.10.1. 
Continuous Glucose Monitoring (CGM) ....................................................................58 
7.10.2. 
Self-monitoring Blood Glucose (SMBG) ...................................................................59 
7.10.3. 
Definition and Classification of Hypoglycemic Events .............................................59 
7.11. 
Patient-Reported Outcome Measurements .................................................................60 
7.11.1. 
Diabetes Treatment Satisfaction Questionnaire (DTSQ) ...........................................60 
7.11.2. 
Audit of Diabetes Dependent Quality of Life Questionnaire (ADDQoL) .................61 
7.12. 
Laboratory Evaluations ...............................................................................................61 
7.12.1. 
Pregnancy Tests ..........................................................................................................62 
7.12.2. 
Immune Panel .............................................................................................................62 

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7.12.3. 
Reserve Blood Samples ..............................................................................................63 
7.12.4. 
Specimen Preparation, Handling, and Shipping .........................................................63 
7.12.5. 
Blood Volumes ...........................................................................................................63 
7.13. 
Simplified Oral Glucose Challenge Test ....................................................................63 
8. 
SAFETY REPORTING ..............................................................................................64 
8.1. 
Adverse Events ...........................................................................................................64 
8.1.1. 
Causality Assessment of Adverse Events ...................................................................65 
8.1.2. 
Expected Adverse Reactions ......................................................................................66 
8.1.3. 
Suspected, Unexpected Serious Adverse Reactions (SUSAR) ..................................66 
8.1.4. 
Unanticipated Problems ..............................................................................................67 
8.1.5. 
Procedures to Be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings .......................................................................67 
8.1.6. 
Adverse Events of Special Interest .............................................................................67 
8.2. 
Serious Adverse Events (SAE) ...................................................................................67 
8.2.1. 
SAE Reporting Procedures .........................................................................................69 
8.2.2. 
Sponsor Reporting Requirements to Regulatory Authorities .....................................69 
8.3. 
Reporting of Pregnancy ..............................................................................................69 
8.4. 
Reporting Period .........................................................................................................70 
8.5. 
Data Safety Monitoring Board (DSMB) .....................................................................71 
8.6. 
Study Stopping Rules .................................................................................................71 
9. 
CLINICAL MONITORING .......................................................................................72 
10. 
STATISTICAL CONSIDERATIONS .......................................................................73 
10.1. 
Study Hypotheses .......................................................................................................73 
10.2. 
Sample Size Considerations .......................................................................................73 
10.3. 
Interim Analysis ..........................................................................................................74 
10.3.1. 
Safety Review .............................................................................................................74 
10.3.2. 
Internal Efficacy and Safety Review ..........................................................................74 
10.4. 
Analysis Plan ..............................................................................................................75 
10.4.1. 
Analysis Populations ..................................................................................................75 
10.4.2. 
Demographic and Subject Characteristics ..................................................................75 
10.4.3. 
Primary Safety Analysis .............................................................................................75 

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10.4.4. 
Primary Efficacy Analysis ..........................................................................................75 
10.4.5. 
Secondary Analyses ....................................................................................................76 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ...............................................................................................77 
12. 
SPONSOR AUDITS AND INSPECTIONS BY REGULATORY 
AGENCIES .................................................................................................................77 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ..................................................77 
13.1. 
Ethical Standard ..........................................................................................................77 
13.2. 
Institutional Review Board (IRB) or Research Ethics Board (REB) .........................77 
13.3. 
Informed Consent Process ..........................................................................................78 
13.4. 
Exclusion of Women, Minorities, and Children (Special Populations) ......................78 
13.5. 
Subject Confidentiality ...............................................................................................78 
13.6. 
Reasons for Withdrawal .............................................................................................78 
13.6.1. 
Handling of Withdrawals ............................................................................................79 
13.7. 
Study Discontinuation ................................................................................................80 
13.8. 
Future Evaluation of Explanted Units ........................................................................80 
14. 
DATA HANDLING AND RECORD KEEPING ......................................................80 
14.1. 
Data Management Responsibilities ............................................................................80 
14.2. 
Data Capture Methods ................................................................................................80 
14.3. 
Types of Data ..............................................................................................................81 
14.4. 
Study Records Retention ............................................................................................81 
14.5. 
Protocol Deviations ....................................................................................................81 
15. 
DATA PROTECTION ...............................................................................................82 
16. 
LITERATURE REFERENCES ..................................................................................83 
17. 
SUPPLEMENTS AND APPENDICES .....................................................................84 
APPENDIX A.  DIABETES TREATMENT SATISFACTION QUESTIONNAIRE 
(STATUS) – DTSQS ...................................................................................................93 
APPENDIX B.  DIABETES TREATMENT SATISFACTION QUESTIONNAIRE 
(CHANGE) – DTSQC .................................................................................................94 
APPENDIX C.  AUDIT OF DIABETES DEPENDENT QUALITY OF LIFE 
(ADDQOL) .................................................................................................................95 
 
 

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LIST OF TABLES 
Table 1: 
SCHEDULE OF ASSESSMENTS [COHORT 1 T1DM; N=3 to 20 
SUBJECTS] ................................................................................................................85 
Table 2: 
SCHEDULE OF ASSESSMENTS [COHORT 2; N=36 to 39 SUBJECTS] .............88 
Table 3: 
SCHEDULE OF ASSESSMENTS [COHORT 1 T2DM; N = Up to 5 
SUBJECTS] ................................................................................................................91 
 

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PROTOCOL SUMMARY 
Title: 
A Prospective, Multicenter, Open-Label, First-in-Human Phase 
1/2 Study with Two Cohorts to Evaluate the Safety, Tolerability, 
and Efficacy of Various Doses of VC-01 Combination Product 
in Subjects with Type 1 Diabetes Mellitus 
Description of Agent or 
Intervention: 
ViaCyte has developed the VC-01 combination product, which is 
intended to control blood glucose in a more physiologic, 
sensitive, and homeostatic manner than the various forms of 
injectable insulin and pump therapies currently available.  VC-
01 combination product is comprised of two distinct 
components: (1) PEC-01 pancreatic endoderm cells derived 
from human embryonic stem cells (hESC) and (2) a durable, 
cell-impermeable, removable, macroencapsulation device known 
as the Encaptra drug delivery system. 
During the first three to six months, the VC-01 units are expected 
to vascularize adequately, and pancreatic progenitor cells are 
expected to differentiate into mature glucose-responsive, insulin-
producing cells, capable of secreting insulin in response to 
serum glucose concentration. 
Subjects may be implanted with VC-01-250 combination product 
for dose finding, and smaller VC-01-20 combination product or 
Comparator sentinels as sentinel units; these are smaller units 
that will be explanted at various time points and examined ex 
vivo. 
Study Design: 
This will be an open-label, long-term, first-in-human (FIH) 
clinical trial in subjects with type 1 diabetes mellitus (T1DM).   
The trial may also evaluate the histological quality of VC-01 in a 
sample of subjects with type 2 diabetes mellitus (T2DM).   
Study Objectives: 
 
Objectives:  This trial will test whether the VC-01 combination 
product can be implanted in anatomical locations involving the 
trunk or extremities and maintained safely for up to two years.  
There are two distinct cohorts in this FIH trial and each 
addresses distinct objectives. 
Cohort 1 Study Objective: 
 Assess the local and systemic safety and tolerability of the 

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VC-01 combination product when implanted into otherwise 
healthy subjects with type 1 diabetes mellitus (T1DM) for up 
to Month 24.   
Cohort 2 Study Objectives: 
 Evaluate the clinical efficacy and further assess safety and 
tolerability of the VC-01 combination product from 
implantation to Month 24. 
 Explore effects of weight, gender, BMI, or other potentially 
interacting factors on the responsiveness of the subjects to 
the experimental intervention.  
Cohort 1 and 2 Study Objectives (Exploratory): 
 Optimize the recommended surgical implantation procedure, 
anatomical location, and perioperative care for VC-01.   
 Assess the effects of the host immune response to implanted 
VC-01 units. 
Study Endpoints: 
The study endpoints vary between the two (2) Cohorts and 
include safety, tolerability, and efficacy. 
 Safety endpoints include adverse events (AE), the 
evaluation of the subject’s immune response via serum 
immunoglobulin 
and 
hematological 
assays, 
and 
ultrasound imaging of the implanted products. 
 Tolerability endpoints include the AEs occurring around 
the time of implantation and beyond. 
 Efficacy endpoints include the ability of the VC-01 
combination product to produce insulin, assessed by 
stimulated serum C-peptide measurements, changes in 
usage of exogenous insulin, and measures of glycemic 
control. 
Endpoints: The primary endpoint of safety will be measured by 
the AE profile. The primary and secondary endpoints are noted 
below: 
Primary: 
 
Cohort 1: Adverse event profile: AE reports, possible 

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immune responses (i.e., from the serum immunoglobulin or 
hematological assays), and implantation site assessments 
(e.g., fever, erythema, pain, tenderness, induration) for up to 
four hours post-implantation and at subsequent visits. 
 
Cohort 2: Change from baseline in C-peptide AUC0-4h 
following a Mixed Meal Tolerance Test (MMTT) at Week 26 
Secondary: 
Safety and Tolerability of the VC-01-250 combination 
product over two years as measured by vital signs, physical 
exams, concomitant medications, clinical lab tests, quality of 
life, diabetes treatment satisfaction and number of subjects 
requiring a premature VC-01 combination product explant 
due to safety issues, local tolerability, or malfunctions. 
Efficacy: 
 
Change from baseline in C-peptide AUC0-2h or AUC0-4h 
following an MMTT at Weeks 8, 12, 16, 20, 26 (for 
AUC0-2h), 39, 52, 78, and 104; 
 
Change from baseline in average daily insulin dose in the 
seven days preceding Clinic Visits at Weeks 26, 52, 78, 
and 104; 
 
Change from baseline in frequency of hypoglycemic 
events at Weeks 26, 52, 78, 104; 
 
Time to onset of biological response of C-peptide 
following MMTT; 
 
Percent of subjects who achieve exogenous insulin 
independence; 
 
Percent of subjects who achieve a 50% reduction in 
average weekly exogenous insulin dose at Weeks 12, 20, 
26, 39, 52, 78, and 104; 
 
Change from baseline to Weeks 26, 52, 78, and 104 in 
Patient-Reported Outcome Measure (PROM) scores; 
 
Percent of time spent with blood glucose values at 
various cut points (e.g., ≤70 mg/dL, ≥180 mg/dL) as 
measured 
by 
each 
subject’s 
continuous 
glucose 
monitoring (CGM) device. 
Cohort 2: Implantation site assessments (e.g., fever, 
erythema, pain, tenderness, induration) for up to four (4) 
hours post-implantation and at subsequent visits; and 

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incidence of all AEs reported during the study which includes 
any suspected related immunologic reactions. 
Exploratory (both Cohort 1 and 2): 
 Histological results of explanted units and any associated 
tissue capsule to evaluate cell viability, vascularization, 
immune 
response, 
and/or 
cell 
maturation 
and 
differentiation. 
Population: 
 
A total target of up to approximately 69 otherwise healthy 
subjects will be enrolled into this first-in-human (FIH) clinical 
trial. 
 
Cohort 1 will have at least three (3) and up to approximately 
thirty (30) insulin-requiring diabetic subjects enrolled.  Most of 
these subjects will be T1DM; however up to five (5) subjects with 
T2DM may be enrolled as part of Cohort 1 if the Sponsor 
considers it relevant to understanding the engraftment process in 
the absence of autoantibodies present in T1DM.   A total of 30 
subjects may be enrolled in Cohort 1. 
 
Cohort 2 will have approximately 36 to 39 T1DM subjects 
enrolled.  This gives a total study size of up to 69 subjects. 
 
Note that the data from the T2DM subjects will be collected and 
summarized separately from that for the T1DM subjects.   
 
Phase: 
1/2 
Number of Sites: 
Approximately four to six 
Study Duration: 
Screening period is approximately four (4) weeks.  Enrolled 
subjects with T1DM are expected to have the VC-01 product 
implanted for two years; after all VC-01 units have been 
explanted, each subject will be required to be followed in a 3-
year long-term follow-up study (VC01-201). 
Subjects with T2DM are expected to have the VC-01 product 
implanted for up to approximately six months. 
VC01-101 Subject 
Participation Duration: 
Two (2) years for T1DM subjects. 
Up to seven (7) months for T2DM subjects. 
Estimated Time to 
One to two years recruitment estimated (combined for both 

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Complete Enrollment: 
cohorts) 
 
LIST OF ABBREVIATIONS 
ADDQoL 
Audit of Diabetes-Dependent Quality of Life 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance  
AST 
Aspartate Aminotransferase 
BMI 
Body Mass Index 
CGM 
Continuous Glucose Monitoring 
CHF 
Congestive Heart Failure 
GMP 
Certified Good Manufacturing Procedures 
CRF 
Case Report Form (electronic or paper) 
CRO 
Contract Research Organization 
DSMB 
Data and Safety Monitoring Board 
DTSQ 
 
Diabetes Treatment Satisfaction Questionnaire in status (DTSQs) and 
change (DTSQc) version 
ECG 
Electrocardiogram 
EIU 
Exposure in Utero 
EoP2 
End of Phase 2 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FIH 
First-in-Human 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
hESC 
Human Embryonic Stem Cell(s) 
HIPAA 
Health Insurance Portability and Accountability Act 
HU 
Hypoglycemia Unawareness 
IB 
Investigator’s Brochure 
ICD 
Informed Consent Document 
ICH 
International Conference on Harmonisation 
IEQ 
Islet Equivalents 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
JDRF 
Juvenile Diabetes Research Foundation 
KM 
Kaplan-Meier 
LSLV 
Last Subject Last Visit 
LSM 
Least Squares Mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMTT 
Mixed Meal Tolerance Test 

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N/n 
Number (typically refers to subjects) 
NCI-CTCAE 
National Cancer Institute’s Common Terminology Criteria for Adverse 
Events 
PE 
Physical Examination 
PEC 
Pancreatic Endoderm Cells 
PEC-01 
PEC-01 Cells (drug product) 
PI 
Principal Investigator 
PROM 
Patient Reported Outcome Measures 
PT 
Preferred Term 
QC 
Quality Control 
REB 
Research Ethics Board (Canada) 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SAS 
Safety Analysis Set 
SE 
Standard Error 
SHE 
Severe Hypoglycemic Event(s) 
SMBG 
Self Monitoring of Blood Glucose (i.e., fingerstick) 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SSA 
Site-Specific Amendment 
T1DM 
Type 1 Diabetes Mellitus 
T2DM 
Type 2 Diabetes Mellitus 
TEAE 
Treatment Emergent Adverse Event 
ULN 
Upper Limit of Normal 
UPT 
Urine Pregnancy Test 
US 
United States 
VC-01 
VC-01 Combination Product 

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1. 
INTRODUCTION 
1.1. 
Background Information and Scientific Rationale 
Diabetes mellitus, a life-threatening disease growing at an alarming rate, has more than doubled 
in prevalence over the last thirty years. [REF 1]  In 2012, the number of people worldwide with 
diabetes was estimated to be between 347 and 371 million (approximately 5% of the world’s 
population).  According to the 2011 National Diabetes Fact Sheet from the Centers for Disease 
Control (CDC), there are 25.8 million people of all ages living with diabetes in the United States: 
18.8 million of those being diagnosed and 7 million undiagnosed [REF 2].  Of the people 
diagnosed with diabetes, approximately 5%, or 1 million, have type 1 diabetes mellitus (T1DM) 
and require exogenous insulin injections every day to survive [REF 2].  
The hallmark of diabetes is elevated blood glucose levels.  Over time, this chronic 
hyperglycemia frequently results in both microvascular (retinopathy, neuropathy, nephropathy) 
and macrovascular (atherosclerosis, cardiac disease) complications, which severely increase 
morbidity and mortality, and diminish the patient’s quality of life.  Treatment costs of diabetes 
and its complications range from $174 billion to $240 billion dollars annually in the US alone, 
and care for people with diagnosed diabetes accounts for greater than one in five health care 
dollars. [REF 2, 3]  Medical care costs for people with diabetes are more than two times higher 
than for those without diabetes [REF 2].   
Diabetes patients who require insulin treatment include all patients with T1DM, which is caused 
by loss of insulin-producing pancreatic beta cell mass, and 20-30% of patients with type 2 
diabetes mellitus (T2DM), who require insulin as adjunctive therapy.  Each year, more than 
15,000 children and 15,000 adults (approximately 80 people per day) are diagnosed with T1DM 
in the US alone [REF 2].  
There is no known way to prevent or cure T1DM [REF 2].  Treatment involves frequent, painful, 
and cumbersome blood glucose monitoring followed by insulin injection.  This standard of care 
can be woefully inadequate.  Subjects employing frequent “fingerstick” blood glucose 
monitoring are able to maintain strict glycemic control within the ADA-specified optimal range 
less than 30% of the time. [REF 4]  The most intensive forms of insulin therapy involve the use 
of Continuous Glucose Monitoring (CGM) systems, self-monitoring (fingerstick) blood glucose 
measurement with portable meters, and implanted insulin pumps.  Yet even these technologically 
advanced systems require significant patient management and cannot control glycemia perfectly.  
Patients using CGM may still be hyperglycemic almost 30% of each day. [REF 4]   
Importantly, insulin therapy also leads to periods of hypoglycemia.  Patients using CGM may be 
hypoglycemic approximately 8% of each day, with a propensity for hypoglycemic events to 
occur at night. [REF 4]  In some cases, severe hypoglycemic events (SHE), i.e., those requiring 
the aid of another person to administer carbohydrates, glucagon, or other resuscitative assistance, 
can lead to seizures, unconsciousness, coma, and death.  Importantly, a history of hypoglycemia 
can predispose patients to episodes of hypoglycemia unawareness (HU), which increases their 
risk of severe hypoglycemia and serious sequelae by at least 6-fold. [REF 5]  Hypoglycemia, like 
hyperglycemia, should be avoided if possible.  

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Many new approaches to treatment of T1DM are being pursued including immunologic 
intervention in disease mechanisms, beta-cell regenerative and/or replacement therapies, and 
engineering solutions to enhanced glucose monitoring and insulin delivery.  One such treatment 
being developed is the pancreatic islet transplant which may employ cells of either porcine or 
human origin.  Although allogeneic islet cell transplantation has achieved insulin independence 
in some patients, the success rate from center to center has varied widely, and the duration of 
effect has been limited.  Furthermore, islet transplant has two significant disadvantages.  First, 
pancreatic islet transplantation requires chronic immunosuppression for the lifetime of the graft, 
which adds substantial risk including severe infection and potential progression of occult 
cancers.  Second, its availability is limited by an insufficient supply of acceptable human 
pancreata as source material. 
1.2. 
Investigational Product 
ViaCyte has developed the VC-01 combination product which is intended to control blood 
glucose in a more physiologic, sensitive, and homeostatic manner than the various forms of 
injectable insulin currently available.  The VC-01 combination product is comprised of two 
distinct components:  PEC-01 pancreatic endoderm cells derived from human embryonic stem 
cells (hESC), and a durable, cell-impermeable, removable, macroencapsulation device (known as 
the Encaptra® drug delivery system).  The VC-01 combination product may be implanted in an 
outpatient procedure.  
The VC-01 combination product may be considered a pro-drug inasmuch as the pancreatic 
progenitor cell component matures to glucose-responsive, insulin-secreting cells only after 
implantation and further differentiation.  The insulin-producing capability of VC-01 increases 
gradually; in nonclinical studies, the product reaches glucose-responsive activity capable of 
regulating host glycemia at two to three months after implantation.  Subcutaneously in rodents, 
the cells in the device differentiate into pancreatic endocrine cells, including those that express 
insulin and release it in a glucose-responsive fashion as well as cells expressing glucagon, 
somatostatin, pancreatic polypeptide, and ghrelin, similar to human islet tissue.  Importantly, 
host vascularization accompanies graft maturation to provide a source for oxygen and other 
nutrients, and a mechanism to deliver insulin and other graft-expressed hormones to the body. 
Glucose-responsive secretion of insulin by a therapeutic dose of the VC-01 combination product 
would be expected to maintain better glycemic control than the current standard of care.  If found 
to be safe and effective, VC-01 may prevent both the acute dangers of hypoglycemic excursion 
(e.g., SHE) and the more chronic complications of diabetes (e.g., microvascular and 
macrovascular disease).  Moreover, VC-01 may alleviate the frequent blood glucose checks and 
insulin injections required each day.  Thus, it is anticipated that VC-01 might significantly 
improve quality of life and treatment satisfaction as compared to currently available therapies. 
PEC-01 is manufactured to satisfy rigorous quality and safety requirements.  The manufacturing 
process was designed to eliminate pluripotent stem cells and produce a highly enriched 
pancreatic endoderm population.   No potentially dangerous cell type has been identified in over 
1,000 VC-01 units implanted in nonclinical animal studies or during the early, limited, clinical 
use of the product in this FIH trial. 

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A unique and important feature of VC-01 is the encapsulation of PEC-01 in the Encaptra drug 
delivery system, which affords numerous benefits noted below.   
 The Encaptra drug delivery system is macroporous, permitting free passage of 
oxygen, nutrients, proteins, and other macromolecules required to maintain the 
implanted cell viability and function.   
 The Encaptra drug delivery system is impermeable to implanted and host cells.  Thus, 
it permanently contains PEC-01 at a defined location, preventing them from 
distributing into host tissue.   
 Once implanted, VC-01 can be monitored via ultrasound for evidence of device 
lumen expansion as an indicator of potentially unsafe, off-target cell growth.   
 The Encaptra drug delivery system also prevents direct contact between the immune 
cells of the host and the cells of the graft.  This physical barrier interferes with 
antigen presentation and disrupts the cell-mediated effector functions of the typical 
immune response.  Similar physical barrier membrane systems have been shown to 
protect cells from allo- and auto-immune rejection [REF 7] as well as to protect 
against sensitization of the host. [REF 6]  In this way, immune-protection afforded by 
the device eliminates the need for, and the attendant safety risks of, chronic 
immunosuppression.   
 Finally, in the event of loss of function, adverse reaction, or other potential safety 
concern, VC-01 units can be promptly removed in an out-patient procedure.  The 
ability to explant the entire graft (and all cells contained in the graft) offers a unique 
safety advantage as compared to other cell therapies in which implanted cells cannot 
be retrieved. 
1.3. 
Nonclinical Information  
1.3.1. 
Evaluation of Safety of PEC-01 Cells 
Nonclinical evaluation of the safety of PEC-01 includes characterization of the source hESC 
starting material, intermediate cell populations during PEC-01 drug substance manufacture, and 
the resulting differentiated pancreatic endoderm cell population.  Evaluations of the hESC 
Master Cell Bank and Working Cell Bank were completed in accordance with applicable 
guidance documents.  For PEC-01 cellular manufacture, raw materials have been subjected to a 
risk assessment and will meet acceptance criteria for Phase 1 clinical manufacturing.  To ensure 
sufficient safety of PEC-01, GMP manufacturing of PEC-01 will be performed in compliance 
with regulations and quality control procedures appropriate for the phase of clinical use.  
Characterizations of PEC-01 include assessment of identity, purity, quality, and stability. 
1.3.2. 
Nonclinical Evaluation of Safety of the Encaptra Drug Delivery System 
Component 
Nonclinical evaluations of the Encaptra drug delivery system include device biocompatibility 
studies and device integrity studies.  Additional testing performed to date has demonstrated that 
the Encaptra device is capable of supporting survival, differentiation, and maturation of PEC-01 

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in vivo.  Feasibility of utilizing the device to prevent biodistribution of implanted cells and to 
provide allogeneic immune protection against host cells has been demonstrated.  Design 
verification activities are focused on confirming that the device membrane maintains its ability to 
block cell migration through the product life cycle, on assessing material stability, and on 
implementing complementary manufacturing quality controls to ensure that all devices produced 
will provide adequate safety performance.  Completed studies, conducted in accordance with 
GLP, confirm that the device passes all biocompatibility tests.  The Encaptra device is expected 
to significantly contribute to the safety profile of the VC-01 product by providing biocompatible 
and biostable encapsulation that prevents implanted cells from directly contacting host tissue. 
1.3.3. 
Nonclinical Evaluation of Safety and Efficacy of VC-01 
Nonclinical evaluations of VC-01 safety and efficacy include three toxicology and 
tumorigenicity studies conducted in accordance with Good Laboratory Practices (GLP).  A total 
of 343 SCID-Beige mice were implanted with VC-01 in these three GLP studies.  Safety 
assessments in these studies included: necropsy with organ weights, full organ panel 
histopathology, histopathology on the implant and surrounding tissue, and clinical pathology 
including blood chemistry, hematology, coagulation analysis, and urinalysis.  The completed 
studies demonstrated excellent tolerability of the graft with an absence of any related toxicity on 
any of these measures, as well as an absence of tumor formation.  Each mouse in these studies 
was implanted with a cell dose approximately 120 times higher, on a per kg basis, than the initial 
dose planned for evaluation in the first-in-human clinical trial (VC01-101), and thus these GLP 
studies represent a robust nonclinical demonstration of VC-01 combination product safety. 
Five (5) different lots of PEC-01 were used in these three GLP studies with no evidence of 
teratoma formation.  However, when Encaptra devices were loaded with PEC-01 “spiked” with 
small proportions of undifferentiated hESC, or loaded with pure undifferentiated hESC (as a 
positive control) and implanted into SCID-Beige mice, teratomas were observed (internal study 
#SR-2012-009; GLP study C12873).  These intentionally generated teratomas were contained by 
the device.  While hESC have not been observed in the PEC-01 cell population, all lots of cell 
product used to manufacture VC-01 for this clinical trial will be QC tested for hESC 
contamination prior to product release, nevertheless, as a safety precaution.  If a teratoma were to 
grow in a device, it would be detected via non-invasive imaging (see Section 7.6).   
Studies conducted under GLP also characterize glucose-responsive human C-peptide secretion 
and the capacity of VC-01 to appropriately regulate host glycemia.  Moreover, each graft is 
examined histologically, including a determination as to whether there are host (mouse) cells 
inside the device.  As host cells always enter a device if they are able, i.e., if there is a breach in 
the device, the absence of host cells within the device demonstrates the integrity, specifically the 
cell impermeability, of the encapsulating device.   
Classical biodistribution studies and pharmacokinetic studies, namely absorption, distribution, 
metabolism, and excretion, are not particularly applicable to the VC-01 product or its cellular 
and encapsulating device components.  Instead, pharmacodynamic studies with the VC-01 
product include a “meta-analysis” of over 250 mice implanted with the VC-01-20 product.  
These studies demonstrate: 
 Consistent kinetics for acquisition of glucose-responsive C-peptide secretion,  

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 C-peptide secretion reaching levels capable of regulating glycemia in the absence of 
endogenous host beta cells,  
 No induction of hypoglycemia, and  
 Maintenance of durable therapeutic properties throughout the duration of 
implantation (commonly six to nine months).   
Also, with VC-01 implanted, mouse non-fasting blood glucose levels are lowered to levels more 
typical of non-fasting human blood glucose, and once achieved, stable blood glucose levels are 
subsequently observed throughout duration of the VC-01 product implant.  Finally, because the 
VC-01 product is designed to deliver PEC-01 within the Encaptra device, the product is readily 
retrievable via an explantation procedure, allowing for immediate cessation of drug delivery if 
indicated.  
Nonclinical efficacy dose-range finding studies have been conducted.  A principal conclusion 
from these studies is that the ultimate therapeutic capacity of the VC-01 combination product is 
not particularly dependent upon the number of cells administered; instead it is dictated by the 
capacity/volume of the encapsulation device.  For example, units of a given size (e.g., VC-01-20) 
ultimately achieve the same level of function whether 1, 3, or 9 million cells are loaded inside 
prior to implantation.  This is likely because the cells can proliferate to fill the device to capacity, 
and therefore can compensate for “under-loading” the device.  Thus, it is expected that the dose 
delivered is established more so by the number and size (capacity) of units implanted than the 
absolute number of cells delivered upon implant.   
1.4. 
Potential Clinical Risks and Benefits 
There has been limited clinical experience with this product such that no definitive risks or 
benefits can be concluded yet.   
In order to participate in this clinical trial, subjects will not be asked to stop their exogenous 
insulin therapy.  Therefore, subjects are not expected to undergo periods of ineffective diabetes 
therapy during study participation.  If the investigational product demonstrates efficacy, 
however, the dosing requirement for exogenous insulin may decrease over time. 
1.4.1. 
Potential Risks 
As there has been limited clinical experience with this product, the potential risks for study 
participation are hypothetical at this stage.  Potential risks are noted below. 
 There are inherent surgical risks during the implantation and explantation (removal) 
of the VC-01 units including pain, bleeding, hematoma, seroma, tenderness, redness, 
and infection.  With any implant procedure, the possibility of migration or extrusion 
of the implant exists, along with the need for explantation.  Steps will be taken to 
minimize the risks and to make the subject comfortable during the procedure with 
anesthetic and post-procedure analgesia. 
 The use of anesthesia itself may cause side effects.  The type(s) of anesthesia used 
during the implantation and explantation procedures will be determined by the 
investigator or surgeon.  Side effects may include, but are not limited to: 

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 Local anesthesia: Stinging and burning for a few seconds before numbing the skin 
and tissues.  Other less likely side effects include nausea, vomiting, dizziness, 
drowsiness, local allergic reactions (e.g., redness, itching, and rash), low blood 
pressure, weakness, severe numbness or tingling, ringing in ears, blurry or double 
vision, slurred speech, metallic taste in mouth, mental status change, muscle 
twitching, and seizures.  
 General anesthesia: Harm to the vocal chords, heart attack, lung infection, stroke, 
trauma to the teeth or tongue, or temporary mental confusion.  Rarely, waking 
during anesthesia or death may occur. 
 Conscious sedation:  Difficulty breathing.  
 After implantation and vascularization of the implanted units, there may be an 
increased risk for hypoglycemic events.  Although the risk for hypoglycemia from the 
grafted units is minimal based upon preclinical results, as the implanted cells begin 
producing insulin, subjects and investigators will need to monitor fingerstick blood 
sugars closely to appropriately decrease the amount of required exogenous insulin.   
 There is a risk that the implanted product will have a shorter than expected duration 
of efficacy or does not work as expected.  The maximal duration of the VC-01 
combination product exposure that can be feasibly tested pre-clinically is nine 
months; this duration coincides with the lifespan of suitable animal models.  Cell 
viability and product function of the VC-01 unit exceeds the lifetime of animal 
models.  The duration of exposure proposed for this clinical trial is two years.  There 
are safety-related, strictly-defined stopping and explant rules noted in Section 8.6.  
 There are risks that the implanted product may limit the subject’s ability to be a 
candidate for future islet cell transplantation. 
 There is a potential hypothetical risk of off-target cell growth (e.g., teratomas).  
Ultrasound monitoring of the implanted units will occur throughout the trial. 
 There is a potential risk of immune reactions and inflammatory responses due to the 
implantation of the graft.  Steps have already been taken in the design of the device to 
minimize/eliminate this risk, but as the grafts have not yet been studied in a human 
population, there remains a potential risk. 
 There is a potential that the implanted units may rupture or break.  Completed 
cadaver study data indicate that an implanted Encaptra device can sustain the force of 
a baseball traveling at speeds of 60 miles per hour without damage (internal Sponsor 
study).  However, the device will not prevent penetration by a sharp object (e.g., 
insulin needle).  If the device membrane were to be breached, the most likely effect 
would be a loss of efficacy. 
 As human cells are being implanted, there is also a small risk that the subject could 
contract a disease or condition transmitted through the allogeneic cell line. 

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1.4.2. 
Known Potential Benefits 
As VC-01 has not been studied clinically beyond the early stages of this trial, there are no known 
benefits.  However, there may be several potential benefits of this therapy noted below.  
 Improved glycemic control 
 Reduction in exogenous insulin dose 
 Reduction in the number of insulin injections and/or complete elimination of 
exogenous insulin injections 
 Reduction in frequency of blood glucose monitoring 
 Reduction in the number of hypoglycemic events 
 Reduction in the risk of micro- and macro-vascular complications 
 Improvement in Quality of Life from an economic standpoint (e.g., decreased 
exogenous insulin requirements, fewer self-monitoring blood glucose supplies) 
 Improvement in Quality of Life from a lifestyle standpoint (e.g., dietary freedom) 
 Improvement in Diabetes Treatment Satisfaction 
The planned number of VC-01 combination products implanted in Cohort 2 is higher than the 
planned number of units implanted in Cohort 1.  While subjects enrolled in Cohort 2 will have a 
higher likelihood of experiencing clinical benefit, it is possible that subjects in Cohort 1 may 
experience some degree of clinical benefit as well.  
2. 
OBJECTIVES AND ENDPOINTS 
This first clinical trial will test whether VC-01 can be implanted and maintained safely for at 
least two years in T1DM subjects.  During the first three to six months, the Encaptra device is 
expected to vascularize adequately, and pancreatic progenitor cells are expected to differentiate 
into mature glucose-responsive, insulin-producing cells, capable of secreting insulin in response 
to serum glucose levels.  This device is anticipated to block direct antigen presentation and 
disrupt cell-mediated effector functions of both the auto- and allo-immune response.   
The safety endpoints will be measured by the AE profile.  In addition, potential decreases in the 
number of hypoglycemic events will be evaluated as this is expected to be one of the first clinical 
indications that the implanted product is exerting a clinical response.  Other endpoints may 
include the ability of VC-01 to produce insulin, assessed by serum C-peptide measurements, 
changes in usage of exogenous insulin, and measurements of glycemic control.  The subject’s 
immune response will be evaluated via serum immunoglobulin and hematological assays.  
On an exploratory basis, the recommended surgical technique, anatomical implant location, and 
perioperative care associated with VC-01 implantation will be evaluated through histological 
analysis of explanted units and any associated tissue capsules.  Furthermore, a histological 
evaluation of explanted VC-01 units in T1DM and T2DM patient populations will provide 
comparative data of the host immune response to the implanted units since the autoantibodies 
associated with T1DM are not present in the T2DM population. 

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2.1. 
Study Objectives 
There are two distinct cohorts in this FIH trial and the cohorts serve different objectives.   
Cohort 1 Study Objective (for Subjects with T1DM): 
 Assess the local and systemic safety and tolerability of VC-01 when implanted into at 
least three (3), and up to approximately 30, otherwise healthy subjects with type 1 
diabetes mellitus (T1DM) enrolled  to Month 24.  Although up to five (5) T2DM subjects 
may also be enrolled during the Cohort 1 period (in lieu of the same number of T1DM 
subjects), all data from the T2DM subjects will be summarized separately from the 
T1DM subjects enrolled in Cohort 1 (Section 10). 
Cohort 2 Study Objective:  
 Evaluate the clinical efficacy and further assess safety and tolerability of the VC-01 
product when implanted into approximately 36 otherwise healthy subjects with T1DM 
enrolled in parallel to Month 24.  Data from different parameters will be evaluated to 
understand whether there are effects based on weight, gender, BMI, or other confounding 
factors.  
Cohort 1 and 2 Study Objective (Exploratory): 
 Optimize the recommended implantation surgical technique, anatomical location(s), and 
perioperative care based on the data collected on Cohort 1 and Cohort 2 subjects.  
Updates to the recommended surgical implantation procedures will occur as needed after 
consultation between the Sponsor and Investigator and/or Site Surgeon and will be 
communicated to the sites to support the safety, tolerability, and efficacy profile of VC-
01.  
 Assess the effects of the host immune response to implanted VC-01 units. 
2.2. 
Study Endpoint Measures 
The study endpoints vary between the two cohorts and include safety, tolerability, and efficacy. 
Additionally, there is an exploratory endpoint related to the surgical implantation procedure and 
anatomical locations of VC-01, perioperative care, and host immune response, which includes 
both Cohorts (Section 2.5).   
 Safety endpoints include AEs over two years and include the evaluation of the 
subject’s immune response via serum immunoglobulin and hematological assays and 
ultrasound imaging of the implanted products.  
 Tolerability endpoints include AEs occurring around the time of the surgical 
implantation and beyond.  
 Efficacy endpoints include the ability of VC-01 to produce insulin, assessed by serum 
C-peptide measurements following a Mixed Meal Tolerance Test (MMTT), changes 
in recorded usage of exogenous insulin and other measures of glycemic control.   

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As a measure of both safety and efficacy, potential decreases in the number of hypoglycemic 
events (HE; SHE) will be evaluated as this is expected to be one of the first clinical 
manifestations of efficacy that may occur at marginal doses.  
2.3. 
Primary Endpoint Measures 
Primary Endpoint / Cohort 1: 
 Adverse Event profile: Incidence of all AEs reported during the study.  This includes 
any suspected related immunologic reactions. 
Primary Endpoint / Cohort 2: 
 Change from baseline in C-peptide AUC0-4h following an MMTT at Week 26. 
2.4. 
Secondary Endpoint Measures 
Secondary Safety and Tolerability Endpoints: 
 Vital signs. 
 Physical examinations. 
 Concomitant medications. 
 Clinical lab tests. 
 Number of subjects requiring a premature explant of the VC-01 product due to safety 
or tolerability issues or malfunction. 
 Implantation site assessments (e.g., fever, erythema, pain, tenderness, induration) for 
up to four hours post-implantation and at subsequent visits. 
Secondary Efficacy Endpoints: 
 Change from baseline in C-peptide AUC0-4h following an MMTT at Weeks 52 and 
104; and change from baseline in C-peptide AUC0-2h following an MMTT at Weeks 
8, 12, 16, 20, 26, 39, 52, 78, and 104. 
 Change from baseline in average daily exogenous insulin dose in the seven days 
preceding Clinic Visits at Weeks 26, 52, 78, and 104. 
 Change from baseline in frequency of hypoglycemic events at Weeks 26, 52, 78, 104.  
 Time to onset of biological response of C-peptide following MMTT. 
 Percent of subjects who achieve exogenous insulin independence; percent of subjects 
who achieve a 50% reduction in average weekly exogenous insulin dose at Weeks 12, 
20, 26, 39, 52, 78, and 104. 
 Change from baseline to Weeks 26, 52, 78, and 104 in Patient-Reported Outcome 
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 Percent of time spent with blood glucose values at various cut points (e.g., < 40 
mg/dL, ≤50 mg/dL, ≤60 mg/dL, ≤70 mg/dL, ≥180 mg/dL, ≥250 mg/dL) as measured 
by each subject’s CGM machine. 
Secondary Safety and Tolerability Endpoint / Cohort 2: 
 Incidence of all AEs reported during the study.  This includes any suspected related 
immunologic reactions. 
2.5. 
Exploratory Endpoint Measures 
Exploratory Endpoint / Cohort 1 and 2: 
 Histological analysis of explanted units and any associated tissue capsules to evaluate 
cell viability, vascularization, cell maturation and differentiation, and the host 
immune response as a means to optimize the surgical implantation procedure, 
anatomical location, perioperative care and assess the host immune response to 
implanted units. 
3. 
STUDY DESIGN 
In this prospective, open-label, multicenter trial, subjects will have up to two or more primary 
VC-01-250 units and one or more smaller sentinel units implanted in anatomical locations 
involving the trunk or extremities (e.g., back, flanks, arm, leg, abdomen, etc.) suitable for 
implantation, as deemed appropriate by the Investigator and/or surgeon after consultation with 
the Sponsor.  Documentation of the implant plan for a subject will be provided to the 
Investigator by the Sponsor.    Implantation will be executed under an anesthetic with or without 
sedation (Section 7.3).  
There are two distinct cohorts in this trial:  
 Cohort 1 (Section 3.1) 
 Cohort 2 (Section 3.2) 
At the end of the up to 2-year treatment period for the T1DM subjects (up to 6 months for T2DM 
subjects), all remaining implanted units will be surgically removed and each enrolled subject will 
be required to participate in a 3-year follow-up (non-intervention) study.  The details of this 3-
year follow-up safety study are established in protocol VC01-201 and may be amended based on 
the data collected in this FIH trial; the primary purpose will be to ensure that there are no long-
term safety issues. 
Each Cohort is described in further detail below. 
3.1. 
Cohort 1 
Cohort 1 may enroll up to approximately thirty (30) insulin-requiring diabetic subjects at one or 
more investigative sites in the US and/or Canada.  Most of these subjects will be T1DM; 
however this may include up to five (5) T2DM subjects.  Subjects in Cohort 1 will have up to 
two of the larger VC-01-250 units implanted, along with four (4) to six (6) of the sentinel units, 

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which may be the smaller VC-01-20 and/or Comparator sentinel.  Up to three (3) of the sentinels 
implanted in each Cohort 1 subject may be a Comparator sentinel that does not contain PEC-01, 
to be determined by the Sponsor with notification to the Investigator.  The implant of 
Comparator sentinels may help identify the host response specific to both the device and cellular 
components of VC-01 (Section 7.9), and implanting up to three (3) Comparator sentinels will 
permit evaluation of changes to the host response over different post-implant time periods, in 
direct comparison to VC-01 sentinel units.       
Each Cohort 1 subject with T1DM will be followed for two years as outlined in Table 1 – 
Schedule of Assessments (Cohort 1).  Cohort 1 subjects with T2DM will be followed for up to 6 
months (26 weeks) as outlined in Table 3. T2DM subjects will be implanted with VC-01 units 
under the same requirements outlined above, but the duration of treatment will be shortened to a 
maximum of 26 weeks.   
For all subjects enrolled during Cohort 1, if a severe, treatment-related AE is spontaneously 
reported to have occurred within the first two weeks of a subject’s implant, subsequent 
implantation of subjects in Cohort 1 may be deferred until formal review of the AE is completed.  
But otherwise, subjects may be concurrently enrolled in Cohort 1. 
After a minimum of three (and up to approximately 30) total subjects in Cohort 1 have reached 
Visit 7 (Week 4), the independent Data Safety Monitoring Board (DSMB) will meet. The 
cumulative data collected from Cohort 1 in all subjects up until that time will be evaluated.  It is 
the DSMB’s decision to trigger the start of Cohort 2.  Given the logistical requirements of 
collecting and cleaning the cumulative data of subjects in Cohort 1, convening a meeting of the 
DSMB to review and approve the data, and the time required to initiate sites participating in 
Cohort 2, the interval from the time the last subject in Cohort 1 is implanted (Visit 3/Day 1) until 
the first subject of Cohort 2 is implanted will be a minimum of 12 weeks.  By such time, it is 
expected that any significant safety signal would present, if one were to exist. 
The DSMB will not meet regularly during Cohort 1 unless the Sponsor seeks an independent 
DSMB review based on Sponsor or Investigational Review Board (IRB) or Research Ethics 
Board (REB) recommendations for managing AEs.  The DSMB chair and/or the entire DSMB 
may receive regular updates as to the progress of the trial. 
3.2. 
Cohort 2 
Cohort 2 will include approximately 36 to 39 T1DM subjects enrolled competitively at 
approximately four to six clinical sites in the US and/or Canada and includes the site(s) enrolling 
subjects into Cohort 1.  Each subject will be followed as outlined in Table 2 – Schedule of 
Assessments (Cohort 2).  The number of VC-01-250 units to be implanted in Cohort 2 subjects 
will be determined by the maximum C-peptide response (basal or stimulated) observed only in 
subjects in Cohort 1 with T1DM  following an MMTT based on available data at the time Cohort 
2 is initiated: 
 If the maximum C-peptide is < 1 ng/mL, six (6) VC-01-250 units and up to three (3) VC-
01-20 sentinel units will be implanted in the Cohort 2 subjects.     
 If the maximum C-peptide is > 1 ng/mL, then four (4) VC-01-250 units and up to three 
(3) VC-01-20 sentinel units will be implanted.   

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 Sentinel units will be explanted at time points to be determined by the Sponsor based on 
information gathered from previously-explanted sentinels.  Generally, it is the intention 
of the Sponsor that subjects enrolled early in Cohort 2 will have some sentinels 
explanted during the early phase of the treatment period.  However, the remaining 
sentinels and subsequent subjects may have sentinels explanted at visits in the latter 
phase of the treatment period.    
The number of VC-01-250 units and VC-01-20 sentinel units implanted into the Cohort 2 
subjects may require adjustment depending on the anatomical locations available for 
implantation.  Individual differences in a subject’s anatomical configuration may result in 
insufficient area available for all of the planned units to be implanted.  The ViaCyte clinical team 
will work with the site Investigator and/or surgeon to confirm the number and location(s) of VC-
01-250 units and VC-01-20 sentinel units to be implanted during Cohort 2 prior to each subject’s 
scheduled implantation.  At the time of implantation procedure, if the scheduled number of units 
cannot be feasibly implanted, then this will be communicated to the Sponsor on the day of the 
surgery and properly documented.   
Cohort 2’s primary efficacy endpoint will be the change of AUC0-4h C-peptide after an MMTT at 
Week 26.   
 
 

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4. 
STUDY POPULATION 
This trial can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into consideration 
when deciding whether this protocol is suitable for a particular subject. 
4.1. 
Number of Patients and Sites 
The subjects in Cohort 1 will be recruited from one or more sites in the United States and/or 
Canada.  A target minimum of three evaluable subjects will be enrolled, but up to approximately 
30 total subjects may be enrolled in Cohort 1 if the Sponsor and/or DSMB determine that 
additional subject data are necessary to properly evaluate the investigational product and/or the 
implantation procedure.  Up to thirty (30) subjects with insulin-requiring diabetes, the majority 
of which will be T1DM subjects but may include up to five (5) subjects with T2DM, may be 
enrolled during Cohort 1.  Cohort 2 will enroll approximately 36 to 39 subjects from 
approximately four to six sites in the United States and/or Canada.  This includes any site(s) 
participating in Cohort 1.  The total enrollment possible for the trial (Cohort 1 and Cohort 2) is 
up to 69 subjects. 
4.2. 
Entry Criteria 
Subject eligibility should be reviewed and documented by an appropriately qualified member of 
the Investigator’s trial team before subjects are included in the trial.  Subjects must meet all of 
the following inclusion criteria at the time of the Screening Visit 1 (unless otherwise specified) 
to be eligible for enrollment into the trial.  If screening laboratory test result(s) exclude a subject 
and the investigator is reasonably certain that the results may be due to a lab error or may have 
been flawed for another reason, the lab test(s) may be repeated once during the screening period 
without prior permission from the Sponsor or its designee. 
4.2.1. 
Inclusion Criteria 
The following inclusion criteria are applicable to all subjects: 
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject has been informed of all aspects of the trial.   
2. Males and females who are non-pregnant and of non-childbearing potential (see Section 
4.5.5.1) ages 18-55. 
3. Cohort 1: Diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus 
(T2DM) for a minimum of 3 years, on a stable (at least 3 months) insulin regimen.  
Subjects with T2DM may also be on an oral anti-diabetic medication regimen.   
Cohort 2: Diagnosis of type 1 diabetes mellitus (T1DM) only for a minimum of 3 years. 
4. Stable, optimized diabetic regimen for at least 3 months.  Variations in the dose of insulin 
are permitted and can still meet the definition of stable insulin dose [refer to the study 
reference manual for additional guidance on acceptable variations].  Subject should be 
under the care of a physician using intensive insulin therapy with therapeutic goals 

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consistent with standard of practice (e.g., American Diabetes Association guidelines) for 
a minimum of 6 months. 
5. The subject is an acceptable candidate for implantation and explantation of VC-01 
combination products as determined by the site surgeon and Investigator. 
6. Willing and able to comply with scheduled visits, treatment plan, post-surgical care and 
restrictions, laboratory tests, fingerstick blood glucose monitoring, and other study 
procedures.   
7. Fluent in English. 
 
The following additional inclusion criteria apply only to subjects with T1DM: 
8. Insulin dosage at screening of ≤1 unit/kg/day (using previous seven days as average). 
9. Willing to use a Continuous Glucose Monitoring (CGM) System as instructed and 
comply with system requirements during the trial.  Note: Use of the standard CGM 
System provided by the Sponsor is required.  
10. Willing and able to comply with daily entries on a study diary. The subject must 
demonstrate compliance with daily entries on the diary between Visits 2 and 3. 
4.2.2. 
Exclusion Criteria 
The following exclusion criteria are applicable to all subjects.  Subjects presenting with any of 
the following will not be included in the trial. 
Disease-specific: 
1. Medical history of islet cell, kidney, and/or pancreas transplant. 
2. Occurrence of two or more severe, unexplained hypoglycemic events (SHE; defined as 
requiring the assistance of another individual) within six months of Visit 3 (Day 
1/Enrollment). 
3. Cohort 1: Known causes of diabetes other than T1DM or T2DM.   
Cohort 2: Known causes of diabetes other than T1DM. 
4. Diabetic complications such as kidney disease (Stage 3 to 5), hypoglycemic unawareness, 
renal dysfunction (macroalbuminuria defined as protein of 2+ or greater on dipstick, 
MDRD eGFR <60 ml/min/1.73m2), previous diagnosis of proliferative retinopathy by 
medical history, diabetic foot ulcers, amputations attributable to diabetes, and/or severe 
peripheral neuropathy. 
5. Widely variable patterns of glycemic control in the clinical judgment of the Principal 
Investigator (PI) [refer to the study reference manual for additional guidance]. 
Medical History: 

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6. Significant skin conditions involving the area(s) targeted for implantation.  Examples 
include but are not limited to recurrent boils/furuncles, extensive surgery or scarring, or 
lipodystrophy. 
7. Subjects routinely consuming >two alcoholic drinks per day or >14 alcoholic drinks per 
week or engages in binge drinking.  One alcoholic drink is defined as 5 oz (150 mL) of 
wine, 12 oz (350 mL) of beer, or 1.5 oz (50 mL) of 80-proof liquor.  Binge drinking is 
defined as a pattern of five or more alcoholic drinks (males) or four or more alcoholic 
drinks (females) in roughly two hours. 
8. Positive urine drug screen for substances of abuse at screening or enrollment visit.  
Infrequent, recreational use of certain substances may be allowed by the PI after 
consultation with the Medical Monitor and/or Sponsor. 
9. Prior history of malignancy with the exception of: 
a. Basal cell carcinoma of the skin; 
b. Squamous cell carcinoma of the skin that has been recurrence free for  
≥five years; 
c. Appropriately treated in situ carcinoma of the cervix.  
10. Known allergies to portions of the cellular excipients used as cell preservation solution or 
the PEC-01 manufacturing process (i.e., bovine, porcine allergies). 
11. History of severe asthma or COPD. 
12. BMI ≥30 kg/m2 or <18 kg/m2 at screening. 
13. Active hepatobiliary disease or an AST or ALT >1.5 x ULN at screening or a total 
bilirubin >1.5 x ULN unless the subject has a history of Gilbert’s disease. 
14. Active infection or known history of Hepatitis B or C. 
15. Positive serology for HIV at screening. 
16. Evidence of previous TB infection (including BCG vaccination or positive PPD). 
17. Other abnormal labs at screening: 
a. Platelets <100,000. 
b. Hgb <12 g/dL (males) or <11 g/dL (females). 
c. Fasting triglycerides >500 mg/dL. 
d. Estimated Glomerular Filtration Rate (GFR) <60 mL/min/1.73 m2 (using MDRD 
calculator) 
e. Clinical lab value outside normal range, unless deemed as not clinically significant by 
the Investigator and Sponsor. 
18. Sustained hypertension defined as average systolic ≥160 mmHg or diastolic ≥90 mmHg 
at screening. 
19. 12-lead ECG findings demonstrating: 
a. QTc>450 msec for males or >470 msec for females at screening. 

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b. Any other abnormality that is clinically significant or is deemed as requiring further 
clinical evaluation by the Investigator. 
20. Any history of unstable angina or Class 3 or 4 CHF, or any of the following 
diagnoses/conditions or procedures within the past year: stroke, myocardial infarction, 
life-threatening arrhythmia, major cardiovascular procedure (e.g., angioplasty, planned 
angioplasty, or carotid endarterectomy), or any other clinically significant cardiovascular 
disease diagnosis or procedure. 
21. History of coagulopathy. 
Exclusionary Procedures, Grafts, or Medication 
22. Immunosuppressant therapy in the previous 30 days and/or requirements for chronic 
immunosuppressive therapy during the study as these may influence the expected action 
of the cells or graft.   
23. Prescribed corticosteroid therapy above physiologic replacement doses in the previous 30 
days. 
24. Participation in a study of an investigational drug, device, or graft within five half-lives 
of the experimental agent or 30 days prior to enrollment in this study, whichever is 
longer. 
25. Planned surgery in the general location of the implanted units (i.e., back and/or flank, 
arms, legs, abdomen, etc.) at any time during study participation. 
Other 
26. In the opinion of the Investigator, the subject is not suitable for the trial. This includes 
clinically significant medical and non-medical conditions, and/or psychiatric disorders. 
The following additional exclusion criteria apply only to subjects with T1DM: 
27. Use of any other diabetes-specific medication other than insulin (any preparation) or 
pramlintide. 
28. A detectable stimulated serum C-peptide from either the Visit 1 lab evaluations or at any 
time-point during the 4-hour screening MMTT conducted at Visit 2, defined as >0.2 
ng/mL (>0.0667 nmol/L). 
4.3. 
Strategies for Recruitment and Retention 
Sites will be evaluated and selected for study participation.  Investigator database review may be 
used as recruitment procedures.  If used, recruitment advertisements and retention materials will 
be approved by IRB/REBs prior to use.   
4.4. 
Treatment Assignment Procedures 
As this is an open-label study, subjects who meet the eligibility criteria will be enrolled into the 
trial on Day 1 and will have the VC-01 combination product surgically implanted on Day 1.  The 
subject, sponsor, and site staff are not blinded and will know how many VC-01 units are being 
implanted depending on which cohort the subject enrolls into.   

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4.4.1. 
Enrollment Procedures 
In Cohort 1, subjects will be enrolled to receive implantation of up to two VC-01-250 units and 
between four to six VC-01-20 or Comparator sentinel units.  
After a minimum of three (and up to approximately 25) Cohort 1 subjects complete Visit 7 
(Week 4), cumulative data will be compiled and reviewed by the independent DSMB.  A DSMB 
approval will be required to continue to Cohort 2.  Approximately 36 to 39 subjects will be 
enrolled into Cohort 2 and receive four or six VC-01-250 units as well as up to three VC-01-20 
sentinel units implanted as described in Sections 3 and 5.   
An electronic or paper-based system will be used to enroll subjects into the trial and will also be 
used as a method of tracking each of the units implanted into the enrolled subjects as each unit 
will have a unique number assigned. 
4.5. 
Lifestyle Guidelines 
Subjects will be instructed concerning the Lifestyle Guidelines described below at the times 
indicated in the Schedule of Assessments Table 1.  In light of several of the items noted below 
which could impact clinic visit procedures, site personnel should remind subjects of these 
restrictions several days prior to their visits. 
4.5.1. 
Dietary Restrictions 
Subjects must abstain from all food and drink (except water) at least 10 hours prior to any blood 
sample collection for clinical lab tests and fasting glucose testing unless otherwise indicated. 
Subjects who do not fast before a scheduled clinic visit will be required to return in a fasted state 
for a clinic visit within the specified visit window.  Any scheduled assessments that do not 
require the subject to be fasting can be performed at the regularly scheduled clinic visit.  Note: 
PROM questionnaires are completed under the same conditions at each visit.  Therefore, if a 
subject does not fast before a scheduled clinic visit, the PROM questionnaires should not be 
administered. 
Subjects will be counseled on appropriate dietary and lifestyle guidelines in accordance with 
local medical standards of care for T1DM or T2DM (as appropriate) at Day 1 (Visit 3) and will 
be asked to follow the advice throughout participation of the trial.  Lifestyle guidance, including 
dietary guidelines, will be reinforced at all visits throughout the trial. 
4.5.2. 
Exogenous Insulin Treatment and Administration 
Subjects will remain on exogenous insulin therapy as appropriate to maintain blood glucose 
control throughout the duration of the study.  Doses of exogenous insulin may be modified over 
the course of the study; however, as much as possible, the types/brands of insulin used by the 
subject should remain consistent.  Also, the insulin injection delivery method for a subject (i.e., 
pump versus multiple daily injections) should not be changed without consulting the Sponsor 
and/or Medical Monitor.  Subjects will be required to log their insulin doses every day.   

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Post-implantation, subjects must agree not to inject their exogenous insulin into the areas near 
the implantation sites.  Additionally, while wearing the CGM sensor, subjects will not inject 
insulin within three (3) inches from the sensor site during sensor wear. 
4.5.3. 
Physical Activity 
For a week post-implantation, subjects will be asked to limit significant physical activity in order 
to ensure optimal healing of the incision sites (e.g., activities using large muscle groups in the 
implantation areas).   
During the first four weeks post-implantation, subjects should avoid exposure to environments 
with temperature extremes (e.g., saunas, spas, ice baths, etc.)   
Subjects should not perform physically strenuous exercise (e.g., heavy lifting, weight training) 
within 48 hours before each blood sample collection for clinical lab tests during the study.  
Moderate activities such as low-distance running, aerobics, bicycling, or swimming are examples 
of acceptable activities in the 48 hours preceding a clinic visit. 
4.5.4. 
Alcohol, Caffeine and Tobacco 
As part of good management of diabetes, the intake of alcohol should be limited (refer to 
exclusion criterion #7 for an acceptable amount of alcohol consumption). 
Ingestion of caffeine will be prohibited for at least 30 minutes prior to the scheduled ECG and 
vital sign determinations. 
Use of nicotine-containing products will be prohibited for at least 30 minutes prior to scheduled 
ECG and vital sign determinations. 
4.5.5. 
Contraception 
No women of childbearing potential will be allowed into the study.  Only women of non-
childbearing potential will be allowed to enroll into this trial.   
All male (in conjunction with any female partner) subjects who, in the opinion of the 
investigator, are biologically capable of having children and are sexually-active, must agree to 
use two acceptable methods of contraception consistently and correctly for the duration of the 
active treatment phase (i.e., while VC-01 is implanted).  The subject will select the most 
appropriate method(s) of contraception from a permitted list (see below).  The investigator or 
designee will instruct the subject in its consistent and correct use.  The investigator or designee, 
at each study visit, will confirm and document consistent and correct use.  In addition, the 
investigator or designee will instruct the subject to call immediately if the selected birth control 
method is discontinued or if a pregnancy is known or suspected in a male subject’s partner.  
Acceptable methods of contraception include: 
 Use of one of the following double-barrier methods:  diaphragm with spermicide and 
a condom; cervical cap and a condom; or contraceptive sponge and a condom 
 Use of hormonal contraception (any registered and marketed contraceptive agent that 
contains an estrogen and/or a progestional agent [including oral, subcutaneous, 
intrauterine and intramuscular agents, and cutaneous patches]) with one of the 

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following: diaphragm with spermicide; cervical cap; contraceptive sponge; condom; 
vasectomy; or IUD. 
 Use of an IUD with one of the following: condom; diaphragm with spermicide; 
contraceptive sponge; vasectomy; or hormonal contraception (noted above). 
 Vasectomy with one of the following: diaphragm with spermicide; cervical cap; 
contraceptive sponge; condom; IUD; or hormonal contraception (noted above). 
4.5.5.1. 
Women – Non-childbearing Potential 
To be considered as non-childbearing potential, women must meet at least one of the following 
criteria: 
 Reached natural menopause (defined as ≥12 months of spontaneous amenorrhea in 
women >45 years of age, or ≥six months of spontaneous amenorrhea by subject 
verbal report with serum follicular stimulating hormone (FSH) levels in the 
postmenopausal range as determined by the central laboratory’s reference range), or 
 Had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or 
occlusion at least six weeks prior to Screening Visit 1 (Week -4). 
4.5.6. 
Other Restrictions 
Subjects should not undergo a magnetic resonance imaging (MRI) scan, computed tomography 
(CT) scan, or diathermy treatment while wearing the CGM sensor.  The CGM, including the 
CGM sensor, should be removed before this type of procedure because of the magnetic fields 
and heat used in these treatments. 
As additional data is gathered in this trial, there may be other restrictions implemented.  These 
restrictions could be related to the efficacy or safety of VC-01.  If required for safety reporting, 
the information will be communicated to sites as quickly as possible in order to inform the 
subjects and/or IRB/REB. 
5. 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
5.1. 
Study Product Description 
5.1.1. 
Acquisition 
PEC-01 drug substance is a cell population largely comprised of pancreatic progenitor and 
immature endocrine cells manufactured via directed differentiation of human embryonic stem 
cells (hESC).  The CyT49 hESC line was derived by ViaCyte from an ethically-consented 
embryo in a process compliant with governing regulations. 
5.1.2. 
Manufacturing, Formulation, Packaging, and Labeling 
The CyT49 hESC line is the starting material for cell product manufacture.  It is the only cell line 
being handled in the GMP manufacturing facility, and the cell line identity is assured via the 
quality process, batch records, and labeling.  Tiered Master and Working Cell Banks have been 

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qualified.  Additional manufacturing information is found in the Chemistry, Manufacturing, and 
Controls (CMC) section of the IND. 
PEC-01 drug substance is manufactured during a 28-day process involving expansion of hESC, 
aggregation into suspension culture, directed differentiation to highly enriched pancreatic 
endoderm cells followed by harvesting and cryopreservation.  The QC testing and release of a 
PEC-01 lot is performed in 2-3 weeks after each lot is cryopreserved.  Studies are underway to 
establish the stability of cryopreserved PEC-01. 
The Encaptra drug delivery system is a polymer sandwich, bonded around its perimeter, which 
forms an encapsulating pouch.  A loading port allows introduction of a cell population into the 
central lumen of an Encaptra device.  The Encaptra device is comprised of polyester 
monofilament mesh, urethane and expanded polytetrafluoroethylene.  The device has passed all 
acute and chronic biocompatibility protocols required by ISO and FDA standards.  After passing 
QC testing, devices are sterilized with ethylene oxide prior to formulation into VC-01 
combination product. 
The PEC-01 and the Encaptra device comprise the VC-01 combination product being 
investigated in this trial.  Note: the VC-01-250 combination product and the VC-01-20 sentinel 
units are made of the same components: PEC-01 and Encaptra device.  The only difference 
between the two units is their size: the larger VC-01-250 unit is roughly half the size of a 
business card and the smaller VC-01-20 sentinel unit is roughly the size of a fingernail.  
Comparator sentinels are identical to the VC-01-20 sentinel unit except that they do not contain 
PEC-01 cells and may exclude specific storage medium excipients that are present in the VC-01 
products.  Sites are not blinded and will be aware of which units contain PEC-01 cells (VC-01-
20 sentinels) and which units are Comparator sentinels.  
Thawed vials of PEC-01 are recovered in culture for three days prior to formulation of the 
combination product.  Following recovery culture, cells are aliquoted into doses, loaded into 
Encaptra devices and sealed into double-sterile packaging within one working shift (eight hours), 
boxed and ready for shipment to investigative sites.  The packaging, labeling, and transport of 
the investigational units and sentinels will be outlined in a study reference manual.  The VC-01 
combination product arrives at the site fully-sealed and ready for implantation into the subject.  
All manufacturing is performed in dedicated GMP clean rooms within ViaCyte facilities in La 
Jolla, CA.  Cell and combination product manufacturing is performed aseptically to minimize the 
risk of contamination.  The GMP cell manufacturing facility is qualified and licensed.   
5.1.3. 
Product Storage and Stability 
The shelf-life of the combined product is qualified for up to seven (7) days.  The shelf-life clock 
starts at the last processing step at the manufacturing facility.  For this FIH study, the goal is to 
have all units implanted no more than four (4) days into the shelf-life, if possible, in order to 
optimize product biologic function.  The “Use By Date” will be present on each unit. 
The temperature of the product is maintained in a temperature-controlled, tested, and qualified 
environmental shipping container.  Up to three units can be shipped together in a single 
environmental shipper.  Depending on the desired number of implants for a given patient, two or 
more shippers will be required. 

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5.1.4. 
Transport of Investigational Product to Site 
The central manufacturing facility at ViaCyte will ship the investigational product and sentinels 
to the site where the surgeon investigator will perform the implantation.  Units will be 
appropriately labeled and shipped, with each shipper containing implants for a single patient.  
The insulated product packaging used for shipping is capable of maintaining the target 
temperature range (18-25C) for the duration of the shelf-life so it is recommended to keep all 
units within their environmental shipper cartons until just prior to implantation into the subject.  
The site will open the shipment to inspect the temperature logger and product package integrity.  
The site will contact ViaCyte immediately if there are noted irregularities or suspected damage to 
the product.  The suspect product should not be implanted into the subject without approval 
by the Sponsor.  ViaCyte or designee may wish to retrieve the damaged product and/or shipping 
containers so an appropriate evaluation can be done.  After implantation, all environmental 
shippers and temperature loggers shall be returned to ViaCyte, Inc. 
Further details will be outlined in a study reference manual. 
5.2. 
Dosage, Preparation, and Administration of Product 
Assuming the safety data from Cohort 1 support a dose increase, the subjects in Cohort 2 are 
anticipated to be implanted with four or six VC-01-250 units, which represents as much as a half 
log increase over Cohort 1.  Furthermore, Cohort 2 subjects will receive up to three VC-01-20 
sentinel units.  It is estimated that each of the VC-01-250 units will contain approximately 40 
million cells and that each of these units will deliver approximately 30,000 to 45,000 islet 
equivalents (IEQ) after in vivo maturation (which is hypothesized to require approximately three 
months).  These mature, encapsulated cells are expected to secrete measurable levels of serum C-
peptide.  It is anticipated that approximately 200,000 IEQ, equivalent to approximately 20% of 
normal beta cell mass, are required to achieve insulin independence. 
The preparation of the investigational product at the site will be detailed in a study reference 
manual.  Step-by-step guidelines on how to handle the units are specified in the manual. 
The administration of the investigational product is performed by implantation on Visit 3 (Day 
1).  The implantation procedures follow step-by-step instructions which are outlined in a study 
reference manual.  Site personnel will be expected to participate in a training program to ensure 
compliance with the product handling and implantation procedures.   
5.3. 
Modification of Study Intervention for a Subject 
Due to the nature of the product under investigation, “dose” adjustments (i.e., an increase or 
decrease) of the implanted VC-01-250 units are not permitted.  However, at the discretion of the 
Sponsor and after consultation with the site investigator, or if a unit is suspected of 
malfunctioning or being damaged (Section 7.8), explantation of one VC-01-250 unit is allowed 
at any time post-implant for a subject.   
Depending on the experience of each subject, the Investigator or subject may elect to have the 
subject withdrawn from the study and have the VC-01-250 units and all remaining VC-01-20 
and/or Comparator sentinel units explanted. 

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Upon explantation of all remaining units at the conclusion of the subject’s participation in the 
trial, if a unit is demonstrated to be malfunctioning and/or did not perform as expected, this 
observation will be documented and communicated to ViaCyte.  Specific procedures relating to 
this topic will be outlined in a study reference manual. 
5.4. 
Accountability Procedures  
The VC-01-250 units and VC-01-20 and/or Comparator sentinels will be distributed to sites in 
preparation for implantation procedures on Enrollment/Day 1.  The Investigator or designee must 
acknowledge receipt of the units either electronically or by hard copy.  Unused or partially used 
supplies must be returned or destroyed, and accounted for as directed in a study reference 
manual.  The Investigator is responsible for the accountability of all used and unused study 
supplies.  There will be a system designed to track and manage the clinical supplies. 
5.5. 
Assessment of Investigational Product Subject Compliance  
As VC-01 is implanted into each subject, assessment of subject compliance with the 
investigational product does not apply. 
If, however, the expected number of VC-01-20 and/or Comparator sentinels or VC-01-250 units 
is not implanted into a subject, this will be captured on a Case Report Form (CRF).   
5.6. 
Concomitant Medications/Treatments 
The surgeon or investigator, in consultation with the Sponsor, may prescribe concomitant 
medication or treatments (e.g., short term regimens of non-steroidal anti-inflammatory drugs, 
high-dose steroids, other anti-inflammatory regimens, immunosuppressants, compression 
garments, and negative pressure systems) to be taken by the subject in order to aid with the 
implant healing and engraftment process.   As additional data are gathered in this trial, changes 
in required concomitant medications and/or treatments may be necessary to enhance safety 
and/or efficacy of VC-01.  The Sponsor will notify the sites and REB/IRB (if necessary) of such 
changes as the information becomes available.   
All concomitant medications, treatments, and procedures will be captured on a CRF during study 
participation.  
For details related to use of exogenous insulin, refer to Section 4.5.2.  
6. 
 
STUDY SCHEDULE 
The visit schedule for enrolled subjects is outlined in the Schedule of Assessments Tables as 
follows: 
 Cohort 1 Subjects with T1DM: Table 1 
 Cohort 2 Subjects: Table 2 
 Cohort 1 Subjects with T2DM: Table 3 

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To minimize variability in the data, site personnel should attempt to schedule each subject’s 
visits at approximately the same day of the week and the same time of day for that subject 
throughout the trial.  For the procedures described below, where multiple procedures are 
scheduled at the same visit, the following chronology of events should be adhered to where 
possible: 
 Patient-Reported Outcome Measure (PROM) instruments  
 12-lead ECG: obtain prior to vitals, blood samples 
 Vital signs (sitting blood pressure, pulse, and temperature): obtain prior to blood 
samples 
 Blood and urine samples 
 Mixed Meal Tolerance Test (with associated blood draws).  For any visits requiring 
both an MMTT and an explant procedure, it is acceptable to perform the MMTT on a 
separate day prior to the explant procedure, but no more than five (5) days prior to the 
explant procedure.   
 Explant procedures:  VC-01-20 and/or Comparator Sentinel units and VC-01-250 
units.  For all implanted sentinels in Cohort 1 and Cohort 2 subjects, the explants will 
occur at time-points to be determined by the Sponsor. 
Other procedures: all other procedures may be obtained in any order either prior to blood 
samples or after; but not sooner than PROMs, ECG, or vitals. 
Ultrasounds for the purpose of locating the implanted units prior to an explantation procedure 
may be done up to 3 days prior to the explantation. 
In general, Cohort 1 subjects with T1DM and Cohort 2 subjects will follow the same schedule of 
assessments.  There are slight differences in procedures relating to the number of sentinels 
implanted and explanted, and these items are noted below. 
Cohort 1 subjects with T2DM will have up to13 study visits conducted over approximately seven 
(7) months following the schedule outlined in Table 3.  For subjects with T2DM, the following 
study procedures are not applicable and can be disregarded where listed in Sections 6.1 through 
6.17: 
• 
PROM instruments 
• 
MMTTs 
• 
Continuous glucose monitoring (CGM) 
• 
Diary completion 
6.1. 
Screening Visit 1 (Week -4 to Week -3) 
It is permissible for the screening visit to occur over several days.  Subjects will be instructed to 
arrive at the site after an overnight fast in order to have the blood tests done at the Screening 
Visit.  At this visit, the following procedures will be completed: 

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 Obtain informed consent (Note: it is acceptable for consent to be obtained prior to the 
screening visit).  
 Collect demography, medical history including smoking status, alcohol frequency, 
and hormonal status, as well as prior and concomitant medications used. 
 Obtain contact information for subject’s health care provider and family members in 
order to reach subject if other contact methods are unsuccessful. 
 Measure height and body weight; perform a complete physical exam including drug 
screen. 
 Obtain a 12-lead ECG. 
 Obtain vitals. 
 Obtain fasting blood samples and urine specimens as outlined in the Schedule of 
Assessments. Provide subject with appropriate supplies to take home in preparation 
for the baseline urine sample to be taken on the morning of screening Visit 2 (Week -
3). 
 Conduct a simplified oral glucose challenge test (Section 7.13) to evaluate stimulated 
C-peptide.    
 Site will review eligibility criteria to assess suitability for the trial.  Note: if a lab 
value is outside the protocol-specified entry criteria, the site may bring the subject 
back to re-test that particular lab value without prior permission from the Sponsor.   
 Review Lifestyle Guidelines. 
 Contact the Sponsor to schedule provisioning of VC-01 for an implant procedure 
date.  For additional details on the notification process, refer to the study reference 
manual. 
6.2. 
Screening Visit 2 (Week -3 to Week -2) 
Subjects appearing to meet eligibility criteria will return for Screening Visit 2 (Week -3).  
Subjects must be fasted for this visit.  At this visit, the following procedures will be completed: 
 Review eligibility criteria. 
 Administer Patient-Reported Outcome Measure (PROM) instrument (DTSQs and 
ADDQoL).  Note: Not required for T2DM subjects. 
 Obtain weight/vitals. 
 Obtain blood samples (according to the schedule of events); collect the urine sample 
from the first morning void taken at home [for albumin/creatinine ratio (this is the 
first of the duplicate baseline samples)]. Provide subject with appropriate supplies to 
take home in preparation for the second baseline urine sample. 

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 Perform 4-hour MMTT with blood draws at 0, 30, 60, 90, 120, 180, 240 minutes.  
This will serve as the baseline MMTT for the efficacy evaluations.  Note: Not 
required for T2DM subjects. 
 Provide CGM machine, supplies and provide instructions for use and care.  It is 
recommended that the subject insert the sensor at the clinic.  The site personnel 
should confirm the CGM equipment appears to be functioning appropriately prior to 
the subject leaving the clinic.  Note: Not required for T2DM subjects. 
 Provide Self-Monitoring of Blood Glucose (SMBG) portable meter, supplies, and 
provide instructions for use and care.  Use of the meter provided by the Sponsor is 
required.  Note: Not required for T2DM subjects. 
 Provide study diary and instructions for use and care.  This is where the subject will 
capture daily insulin doses, details on hypoglycemic event(s), and SMBG fingerstick 
values.  Remind subject that in order to remain eligible for the trial, daily 
compliance with entries between Visit 2 and 3 must be demonstrated.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 
 Contact the Sponsor to report any schedule changes or updates to the implant date.  
For additional details on the notification process, refer to the study reference manual. 
The total Screening Period is expected to last approximately four weeks total.  However, there 
may be situations in which an extension of the Screening Period beyond four weeks is warranted.  
If the Enrollment Visit 3 is scheduled to occur beyond five weeks (>35 days) of the occurrence 
of Screening Visit 1, sites should contact the Sponsor or designee before proceeding.  Depending 
on the expected duration of the delay in conducting Visit 3, an Unplanned Visit may be required 
to perform certain, repeat screening procedures or the subject could be requested to undergo 
complete re-screening. 
The total Screening Period may be accelerated, but a minimum of two weeks must elapse 
between Visit 2 and Visit 3. 
6.3. 
Enrollment / Implantation Visit 3 (Day 1) 
Subjects must be fasted for this visit.  At this visit, the following procedures will be completed: 
 Ensure entry criteria continue to be met 
 Administer Patient-Reported Outcome Measure (PROM) instrument (DTSQs and 
ADDQoL).  Note: Not required for T2DM subjects. 
 Obtain weight/vitals. 
 Perform an abbreviated physical exam. 
 For a select group of subjects, obtain photographic documentation of the implantation 
sites (pre-implantation). 

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 Obtain blood samples per Schedule of Assessments, including immune panel and 
urine drug screen; collect the first morning void urine sample for albumin/creatinine 
ratio (this is the second sample for duplicate baseline samples required).  Note:  The 
immune panel blood samples may be collected at any time between Visit 2 and Visit 
3, once the subject’s study qualification is confirmed (Section 7.12.2).  
 Collect and review CGM, SMBG, and diary data and verify subject has demonstrated 
compliance with diary entries; dispense additional supplies.  Note: Not required for 
T2DM subjects. 
 Assess AEs and Concomitant Medications. 
 Prepare subjects for implantation [see study reference manual].  The implantation 
procedure may be done at a separate location than the routine clinic visits. 
 Implant VC-01-250 units and VC-01-20 and/or Comparator sentinel units (the 
number determined by the cohort into which the subject is enrolled). 
 For a select group of subjects, obtain video documentation of the implantation 
procedure (see Section 7.5). 
 Assess subject for up to four hours post-implantation for AEs. 
 For a select group of subjects, obtain photographic documentation of the implantation 
sites (post-implantation). 
 Upon release from the clinic, remind subject to limit significant physical activity in 
order to ensure optimal healing at implantation sites.  Instruct the subject on the 
proper use of any post-implant treatments (e.g., compression garments). 
6.4. 
Visit 4 (Day 2) 
There is a +1 day window for this visit.  At this visit, the following procedures will be 
completed: 
 Perform a targeted physical exam focusing on the implantation site(s). 
 Obtain weight/vitals. 
 For a select group of subjects, obtain photographic documentation of the implantation 
sites. 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 

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 Explant unit(s). 
For a select group of subjects, obtain video documentation of the explantation procedure (see 
Section 7.5). 
Note: Laboratory assessments are not performed at this visit; therefore, the subject does not need 
to be in a fasted state. 
6.5. 
Visit 5 (Day 5) 
There is a +2 day window for this visit.  At this visit, the following procedures will be 
completed: 
 Perform a targeted PE focusing on the implantation site(s). 
 Obtain weight/vitals. 
 For a select group of subjects, obtain photographic documentation of the implantation 
sites. 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
Note: laboratory assessments are not performed at this visit; therefore, the subject does not need 
to be in a fasted state. 
6.6. 
Visit 6 (Week 2) 
There is a ±2-day window for this visit.  At this visit, the following procedures will be 
completed: 
 Obtain weight/vitals. 
 Perform an abbreviated PE. 
 Obtain blood samples. 
 For a select group of subjects, obtain photographic documentation of the implantation 
site(s). 

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 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.7. 
Visit 7 (Week 4) 
Note: After a minimum of three (and up to approximately 25) subjects in Cohort 1 have reached 
this Week 4 visit, all available data will be evaluated by the DSMB in order to trigger the 
enrollment phase of Cohort 2. 
There is a ±3-day window for this visit.  At this visit, the following procedures will be 
completed: 
 Obtain weight/vitals. 
 Perform an abbreviated PE. 
 Obtain blood samples (including immune samples).  Note:  Ensure the collection time 
of immune panel samples meets requirements (Section 7.12.2). 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 
 Perform (safety) ultrasound assessment of implantation sites.  For Cohort 1, this could 
be done with the (location) ultrasound assessment done prior to the explantation 
procedure. Note: If the ultrasound is performed on the day of the clinic visit, it must 
be done after the vitals, PE, and blood samples are collected.  
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation (and would include a safety 
assessment). 
 Explant unit(s). 

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 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.8. 
Visit 8 (Week 8) 
There is a ±7-day window for this visit.  Subjects must be fasted for this visit.  At this visit, the 
following procedures will be completed: 
 Obtain weight/vitals. 
 Obtain blood samples. 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications.  
 Perform (safety) ultrasound assessment of implantation sites. 
 Conduct a simplified oral glucose challenge test to evaluate stimulated C-peptide. 
Note:  If the stimulated C-peptide result is measurable (>0.1 ng/mL), perform a 2-
hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes) at an Unscheduled Visit as soon as possible.    MMTT not required for 
T2DM subjects. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.9. 
Visit 9 (Week 12) 
There is a ±7-day window for this visit.  Subjects must be fasted for this visit.  At this visit, the 
following procedures will be completed: 
 Obtain weight/vitals. 
 Perform an abbreviated PE. 
 Obtain blood samples (including immune samples) according to schedule of events.  
Note:  Ensure the collection time of immune panel samples meets requirements 
(Section 7.12.2). 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 

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provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Perform (safety) ultrasound assessment of implantation sites. If applicable, this could 
be done with the (location) ultrasound assessment done prior to the explantation 
procedure.  Note: If the ultrasound is performed on the day of the clinic visit, it must 
be done after the vitals, PE, and blood samples are collected. 
 Assess AEs and concomitant medications. 
If the subject’s stimulated C-peptide levels have remained immeasurable (<0.1 ng/mL) post-
implant: 
 Conduct a simplified oral glucose challenge test to evaluate stimulated C-peptide. 
Note:  If the stimulated C-peptide result is measurable (>0.1 ng/mL), perform a 2-
hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes) at an Unscheduled Visit as soon as possible.   MMTT not required for T2DM 
subjects. 
If the subject’s stimulated C-peptide levels have been measurable (>0.1 ng/mL) at any point 
post-implant: 
 Perform 2-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 
120 minutes).   Note: MMTT not required for T2DM subjects. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.10. 
Visits 10 and 13 (Weeks 16 and 39) 
 
There is a ±7-day window for Visit 10.  There is a ±14-day window for Visit 13.  Subjects must 
be fasted for these visits.  At these visits, the following procedures will be completed: 
 Obtain weight/vitals. 
 Perform a targeted PE if an explant was done at the previous visit. 
 Obtain blood samples 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Assess AEs and concomitant medications. 

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 At Visit 13 only, dispense supplies for the first morning urine void (to be brought to 
the clinic at Visit 14). 
If the subject’s stimulated C-peptide levels have remained immeasurable (<0.1 ng/mL) post-
implant: 
 Conduct a simplified oral glucose challenge test to evaluate stimulated C-peptide. 
Note:  If the stimulated C-peptide result is measurable (>0.1 ng/mL), perform a 2-
hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes) at an Unscheduled Visit as soon as possible.   MMTT not required for T2DM 
subjects.          
If the subject’s stimulated C-peptide levels have been measurable (>0.1 ng/mL) at any point 
post-implant: 
 Perform 2-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 
120 minutes).  MMTT not required for T2DM subjects. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.11. 
Visit 11 (Week 20) 
There is a ±7-day window for Visit 11.  Subjects must be fasted for this visit.  At this visit, the 
following procedures will be completed: 
 Obtain weight/vitals. 
 Obtain blood samples. 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies. 
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.  Note: Not 
required for T2DM subjects. 
 Dispense supplies for the first morning urine void (to be brought to the clinic at Visit 
12). 
 Assess AEs and concomitant medications.  
 Perform (safety) ultrasound assessment of implantation sites.  Note: if the ultrasound 
is performed on the day of the clinic visit, it must be done after the vitals and blood 
samples are collected. 
If the subject’s stimulated C-peptide levels have remained immeasurable (<0.1 ng/mL) post-
implant: 

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 Conduct a simplified oral glucose challenge test to evaluate stimulated C-peptide. 
Note:  If the stimulated C-peptide result is measurable (>0.1 ng/mL), perform a 2-
hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes) at an Unscheduled Visit as soon as possible.  MMTT not required for T2DM 
subjects.          
If the subject’s stimulated C-peptide levels have been measurable (>0.1 ng/mL) at any point 
post-implant: 
Perform 2-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes).  MMTT not required for T2DM subjects.Activities noted below to be performed only if 
an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.12. 
Visits 12 and 14 (Weeks 26 and 52) 
There is a ±7-day window for Visit 12.  There is a ±14-day window for Visit 14.  Subjects must 
be fasted for these visits.  At this visit, the following procedures will be completed: 
 Administer Patient-Reported Outcome Measure (PROM) instruments (DTSQs and 
ADDQoL at both Visits; DTSQc at Visit 14 only).  Note: Not required for T2DM 
subjects. 
 Obtain weight/vitals. 
 Perform a complete PE (visit 12) or an abbreviated PE (visit 14).Obtain 12-lead ECG. 
 Obtain blood samples (including fasting serum lipid panel and immune samples); 
obtain urine sample for albumin/creatinine ratio (on first morning void).  Note:  
Ensure the collection time of immune panel samples meets requirements (Section 
7.12.2). 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies. 
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues.   Note: 
Not required for T2DM subjects. 
 Perform (safety) ultrasound assessment of implantation sites.  Note: If the ultrasound 
is performed on the day of the clinic visit, it must be done after the PROM, vitals, PE, 
and blood samples are collected. 
 Assess AEs and concomitant medications. 
 Perform 4-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 
120, 180, 240 minutes).   Note: Not required for T2DM subjects. 

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For all subjects, activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
For T2DM subjects only: 
 Visit 12 is the end-of-treatment visit.  All remaining VC-01 units are to be explanted 
along with the completion of all other required procedures listed in Table 3. 
 
6.13. 
Visits 15 and 17 (Weeks 65 and 91) 
There is a ±14-day window for these visits. At this visit, the following procedures will be 
completed: 
 Obtain weight/vitals. 
 Obtain blood samples. 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies. 
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues. 
 Dispense supplies for the first morning urine void (to be brought to the clinic at 
following visit). 
 Assess AEs and concomitant medications. 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation.  Note: If the ultrasound is 
performed on the day of the clinic visit, it must be done after the vitals, and blood 
samples are collected. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.14. 
Visit 16 (Week 78) 
There is a ±14-day window for this visit.  Subjects must be fasted for this visit.  At this visit, the 
following procedures will be completed: 
 Administer Patient-Reported Outcome Measure (PROM) instrument (DTSQs and 
ADDQoL). 

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 Obtain weight/vitals. 
 Perform an abbreviated PE. 
 Obtain blood samples; obtain urine sample for albumin/creatinine ratio (on first 
morning void). 
 Collect and review CGM, SMBG, and diary data; dispense additional supplies.  
Ensure subject continues to demonstrate compliance with the diary data entry; 
provide counseling and assistance to subject if there are compliance issues. 
 Perform (safety) ultrasound assessment of implantation sites. 
 Assess AEs and concomitant medications. 
If the subject’s stimulated C-peptide levels have remained immeasurable (<0.1 ng/mL) post-
implant: 
 Conduct a simplified oral glucose challenge test to evaluate stimulated C-peptide. 
Note:  If the stimulated C-peptide result is measurable (>0.1 ng/mL), perform a 2-
hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 120 
minutes) at an Unscheduled Visit as soon as possible.          
If the subject’s stimulated C-peptide levels have been measurable (>0.1 ng/mL) at any point 
post-implant: 
 Perform 2-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 
120 minutes). 
Activities noted below to be performed only if an explant is planned for this visit: 
 Perform ultrasound prior to planned explantation to locate the unit(s); the ultrasound 
can be performed up to 3 days prior to the explantation.  Note: If the ultrasound is 
performed on the day of the clinic visit, it must be done after the PROM, vitals, PE, 
and blood samples are collected. 
 Explant unit(s). 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
6.15. 
Visit 18 (Week 104/Early Termination)  
If a subject withdraws or is discontinued from the study at any time, the procedures outlined in 
Visit 18 (Week 104/Early Termination) should be performed and the subject will be followed in 
the 3-year, follow-up study (VC01-201). 
All subjects will undergo an ultrasound to locate all remaining implanted units  
(VC-01-250 units and VC-01-20 and/or Comparator sentinel units).  The ultrasound can be 
performed up to 3 days prior to the explantation and should include a safety evaluation of the 
remaining implanted units.  Note: If the ultrasound is performed on the day of the clinic visit, it 
must be done after the PROM, vitals, PE, and blood samples are collected. 

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There is a ±7-day window for this visit.  Subjects must be fasted for this visit.  At this visit, the 
following procedures will be completed: 
 Administer Patient-Reported Outcome Measure (PROM) instruments (DTSQs, 
DTSQc and ADDQoL).  Note: Not required for T2DM subjects. 
 Obtain weight/vitals. 
 Obtain 12-lead ECG. 
 For a select group of subjects, obtain photographic documentation of the explantation 
sites (pre-explantation). 
 Perform a complete PE. 
 Obtain blood samples (including fasting serum lipid panel, liver/CK, and immune 
samples); obtain urine sample for albumin/creatinine ratio (on first morning void).  
Note:  Ensure the collection time of immune panel samples meets requirements 
(Section 7.12.2). 
 Collect all necessary study-related equipment. 
 Review CGM, SMBG, and diary data; dispense additional supplies (if necessary).    
Note: Not required for T2DM subjects. 
 Assess AEs and concomitant medications. 
 Perform 4-hour MMTT in clinic with serial C-peptide measurements (0, 30, 60, 90, 
120, 180, 240 minutes).  Note: Not required for T2DM subjects. 
 Prepare subject for explantation procedure (see study reference manual): 
 Explant all remaining VC-01-250 units. 
 Explant any remaining sentinel units. 
 For a select group of subjects, obtain video documentation of the explantation 
procedure (see Section 7.5). 
 For a select group of subjects, obtain photographic documentation of the explantation 
sites (post-explantation procedure). 
 Review mandatory participation expectation for the 3-year, long-term, follow-up 
study (ICD process for follow-up study can be initiated.  Please reference follow-up 
study Protocol VC01-201 for full details.) 
 Remind subject of the follow-up visit 19 (Week 105). 
6.16. 
Follow-up Visit 19 (Week 105) 
There is a ±3-day window for this visit.  All subjects, regardless of whether or not they 
completed the trial, will be seen in the clinic within one week following Visit 18/ET to follow-up 
on any unresolved AEs and to follow-up on the post-explantation experience.   
 Obtain weight/vitals. 

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 Perform a targeted PE of explantation site(s). 
 Assess AEs and concomitant medications. 
 For a select group of subjects, obtain photographic documentation of the explantation 
site(s). 
6.17. 
Unplanned Visits  
Unplanned visits may occur at any time for reasons of subject safety and/or collection of 
additional time-point data.  Possible reasons for unplanned visits include but are not limited to:  
 Adverse event follow-up  
 Abnormal laboratory test follow-up  
 Review of blood sugar values with possible exogenous insulin dose adjustments 
 Additional pre-operative evaluations 
 Post-implant and/ or explant site evaluation (includes evaluation of incision healing) 
 Suture removal post-procedure (if applicable) 
 Repeat or follow-up ultrasound evaluations (safety or location) 
 Explant of a VC-01-250 unit or sentinel unit 
 Perform a simplified oral glucose challenge test 
 Perform a MMTT in clinic with serial C-peptide measurements  
 For a select group of subjects, obtain video documentation of the explantation 
procedure, if applicable (see Section 7.5) 
Data will be collected at all unplanned visits depending on the type of visit conducted.  Note: the 
subject must be in a fasted state if any of the following are to be collected or evaluated:  lipid 
tests, fasting blood glucose measurements, MMTT, or PROM instruments.   
7. 
STUDY ASSESSMENTS 
Every effort should be made to ensure the protocol-required tests and procedures are completed 
as described.  However, it is anticipated that from time to time there may be circumstances, 
outside the control of the Investigator that may make it unfeasible to perform a certain test.  In 
these cases, the Investigator will take all steps necessary to ensure the safety and well-being of 
the subject.  When a protocol-required test cannot be performed, the Investigator or designee will 
document the reason for this and any corrective and preventive actions which will be taken to 
ensure that normal processes are adhered to as soon as possible.   
Any instance of a protocol-required test not being performed at the required time, or within the 
protocol-described time window, will constitute a protocol deviation.  These deviations will be 
captured and reviewed by the Sponsor or designee.  Corrective actions will be put into place to 
prevent future occurrences of deviations, if possible.  

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7.1. 
Clinical Evaluations 
7.1.1. 
Physical Examination 
There are three types of physical exams that will be performed over the course of the study: 
complete, abbreviated, and targeted.  Details of each are described below. 
A complete physical exam will be performed by a physician or other medically-qualified health 
professional. 
 
The 
complete 
exams 
will 
be 
performed 
at 
screening 
Visit 
1  
(Week -4), Visit 12 (Week 26), and the final Visit 18 (Week 104 or early termination).  The 
following body systems to be evaluated for the complete physical exam are: general appearance, 
skin, 
head/eyes/ears/nose/throat, 
heart, 
lungs, 
abdomen, 
extremities, 
neurological, 
back/spinal/flank area, and lymph nodes.  Results must be recorded in the subject’s source 
documents and any significant findings on the screening physical exam must be recorded on the 
Medical History CRF.  Over the course of the study, any clinically significant changes from the 
screening PE must be captured as AEs.     
An abbreviated physical exam will also be performed by a physician or other medically-
qualified health professional.  The abbreviated physical exams will be performed at Visit 3 (Day 
1), Visit 6 (Week 2), Visit 7 (Week 4), Visit 9 (Week 12), Visit 14 (Week 52), and Visit 16 
(Week 78).  The abbreviated exam includes assessment of the heart, lungs, abdomen, extremities, 
and skin [including implantation and/or explantation site(s)]. 
A targeted physical exam will be performed by a physician (either the PI or the site surgeon 
assigned to this protocol) or other medically-qualified health professional and will focus on the 
evaluation of the healing status at the implantation and/or explantation sites.  The targeted 
physical exams will be performed at Visit 4 (Day 2), Visit 5 (Day 5), and Visit 19 (Week 105) in 
addition to any visit following a sentinel explant (e.g., Visit 10, Visit 13), inclusive of an 
unplanned visit if it is related to the post-surgical evaluation.   
Other body systems should be evaluated as per the judgment of the Investigator or as needed to 
evaluate AEs.  It is highly recommended that the same person conduct the same-type of physical 
exams for each subject over the course of the study. 
7.1.2. 
Body Weight 
Body weight will be measured using a standardized scale at each of the visits.  Preferably, weight 
will be taken at approximately the same time of day, after voiding, and while wearing a gown or 
light clothing (no shoes or socks).  Body weight should be reported in either pounds or 
kilograms.  Scales are not being provided to each site.  Subjects should be weighed on the same 
scale throughout the study. 
7.1.3. 
12-lead ECG 
A single, supine 12-lead ECG will be obtained on the site’s equipment at the times noted in the 
Schedule of Assessments.  ECGs should be performed after the subject has rested quietly for at 
least 10 minutes in a supine position and prior to the vital signs and blood collection but after the 
PROM questionnaires have been completed.  The screening ECG will serve as the “baseline” 
ECG for comparison.  All ECGs collected during the trial (planned and unplanned) should be 

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reviewed at the site for safety monitoring.  The Investigator is responsible for retaining all copies 
of the ECG reports. 
Any significant findings on the screening ECG must be recorded on the Medical History CRF.  
Over the course of the study, any clinically significant changes from the screening ECG must be 
captured as AEs.     
7.1.4. 
Vitals:  Sitting Blood Pressure, Pulse Rate, and Temperature 
Vital sign measurements include a single measurement of sitting blood pressure, pulse rate, and 
temperature.  BP and pulse rate should be measured on the site’s equipment using either an 
automated device or a manual one.  The following method should be used to record sitting blood 
pressure and pulse rate for subjects. 
 Subjects will refrain from nicotine-containing products and/or ingesting of caffeine 
for at least 30 minutes prior to the measurements. 
 Subjects should be seated in a chair with their backs supported, feet flat on the floor, 
and arms bared and supported at heart level. 
 The appropriate cuff size must be used to ensure accurate measurement and used 
consistently throughout the study. 
 Measurement should be taken on the same arm at each visit; preferably on the non-
dominant arm. 
 Measurement should begin after at least five minutes of rest. 
 Assessment of pulse rate can be manual or automated; however, when done manually, 
the rate should be counted in the brachial/radial artery for at least 30 seconds. 
Other procedures should not be performed during the time of the blood pressure and pulse rate 
measurements. 
7.2. 
Mixed Meal Tolerance Test (MMTT)  
A 4-hour standard mixed meal tolerance test (MMTT) after an overnight fast will be conducted 
during Visit 2 (Week -3).  Additional 2- or 4-hour MMTT will be conducted at Visit 8 (Week 8), 
Visit 9 (Week 12), Visit 10 (Week 16), Visit 11 (Week 20), Visit 12 (Week 26), Visit 13 (Week 
39), Visit 14 (Week 52), Visit 16 (Week 78), and Visit 18/ET (Week 104).  Four-hour MMTT 
will be conducted at the following visits:  Visit 2 (Week -3), Visit 12 (Week 26), Visit 14 (Week 
52), and Visit 18 (Week 104).  Two-hour MMTT will be conducted at all of the other visits only 
after a subject has a measurable C-peptide result (>0.1 ng/mL) from a simplified oral glucose 
challenge test post-implant (Section 7.13).  For any visits requiring both an MMTT and an 
explant procedure, it is acceptable to perform the MMTT on a separate day up to 5 days prior to 
the explant procedure.   
MMTTs are conducted after all other laboratory tests, PROM instruments, and vital signs 
evaluations have been collected.  The MMTT test should be started prior to  
10 AM.  All MMTT supplies will be provided by the Sponsor or designee.  Basal exogenous 
insulin will be continued during the test, but any short-acting insulin will be withheld starting 

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four hours prior to starting the test.  Prior to initiating the MMTT, the subject’s fasting glucose 
will be tested at the site, and the value must be within 70-200 mg/dL in order to begin the 
MMTT.  If a subject’s fasting glucose is not within range and the site feels as though it is 
reasonable to recheck, then one recheck can be done while the subject is in the clinic.  If the 
subject’s fasting glucose is not within the 70-200 mg/dL range, then s/he must return to the site 
within the visit window and attempt the MMTT again. 
For convenience, an intravenous catheter can be placed in a patent vein in the subject’s arm for 
the collection of blood samples.  Insertion of the catheter should be performed at least 30 
minutes prior to any blood collections on the days that the MMTTs will be performed. 
Baseline blood samples will be drawn for measurement of glucose and C-peptide within 
approximately five minutes prior to the administration of the meal test.  At time = 0, the subject 
will then be administered a standard meal consisting of one nutrition drink (Boost® Hi-Protein 
drink, 6 mL/kg body weight to a maximum of 360 mL) The entire amount of Boost® must be 
ingested within 15 min.   
Additional samples for glucose and C-peptide are then collected at 30, 60, 90, and 120 minutes 
after the start of the Boost® meal test for the 2-hour MMTT (Weeks 8, 12, 16, 20, 39, 78) and at 
30, 60, 90, 120, 180, and 240 minutes after the start of the Boost® meal test for the 4-hour 
MMTT (Weeks -2, 26, 52, 104).   
The subjects should sit upright during the test.  Slow walking is permitted, but vigorous exercise 
should be avoided. 
MMTTs are not required for subjects with T2DM. 
Further details will be outlined in the study reference manual. 
7.3. 
Implantation Procedure  
Implantation occurs at Visit 3 (Day 1).  All subjects will have up to two or more primary VC-01-
250 units and up to one (1) or more smaller sentinel units implanted.  All units will be implanted 
in anatomical locations involving the trunk or extremities (e.g., back, flanks, arm, leg, abdomen, 
etc.) suitable for implantation, as deemed appropriate by the Investigator and/or surgeon after 
consultation with the Sponsor.   
For Cohort 1 subjects only, up to three (3) of the sentinels implanted in each subject may be a 
Comparator sentinel that does not contain PEC-01.    Allowance for the implant of a Comparator 
sentinel unit may help identify the host response specific to the device and cellular components 
of VC-01 (Section 7.9). 
Implantation will be executed via incision followed by pockets formed for each implant under 
anesthetic.  Local anesthesia with sedation may be utilized, with use of general anesthesia at the 
discretion of the protocol-trained surgeon.  All medications administered during the implantation 
procedure are to be captured in the source documents and CRF.  Use of cauterizing tools should 
be avoided whenever possible and limited to control of bleeding (i.e., not to be used to form the 
pockets).   Custom pocket sizing tools may be provided by ViaCyte for each unit type to verify 
pocket geometry and size prior to implant placement.  All implants require a minimum of 10 mm 
separation from adjacent units.  Placement of the implanted VC-01-250 and sentinel units should 

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be planned such that explantation of the sentinel units will not disrupt neighboring units.    
Custom tools may be provided by ViaCyte to facilitate device placement into the formed tissue 
pockets. Incisions are expected to be approximately 40 to 50 mm in length, but could vary.  It is 
expected that subjects may have up to approximately five (5) independent incisions in order to 
place the requisite number of units.  Surgeons trained on the procedure will have discretion on 
the ultimate number and length of incisions.  As much as possible, all implant procedures 
performed for subjects at one site should be conducted by the same surgeon. 
A detailed description of the location for implantation and the surgical technique to be used for 
implantation will be provided as part of a study reference manual and site training.  Site 
personnel are required to be trained on the implantation procedure and handling of all 
investigational product prior to the procedure.   
Details on the surgical implantation and location of each implanted unit will be collected on a 
source document and reported on a CRF.   Data collected from implantation surgeries and any 
explantation procedures will help inform the most appropriate implantation procedure to be 
followed (e.g., separation and/or location of implanted units, number of incisions, dissection 
technique).  As this is a FIH study, there is the possibility that the implantation procedures will 
be modified based on the data collected on Cohort 1 or Cohort 2 subjects.  Updates to the 
surgical implantation procedures will occur as needed during the study and communicated to the 
sites to support the safety, tolerability, and efficacy profile of VC-01.  If additional training to the 
sites is required, it will be provided. 
Post-implant, concomitant therapy and/or treatments may be prescribed to facilitate the 
implantation healing and engraftment process (Section 5.6).  The subject will remain in the clinic 
for up to four hours following the procedure to monitor for AEs.  Thereafter, release or extended 
observation of the subject is at the discretion of the surgeon and/or Investigator.  Upon discharge, 
the subject should be reminded of the required Lifestyle Guidelines (Section 4.5).  
Adverse events and the Investigator’s assessment of causality to the implantation procedure (vs. 
the implanted product itself) will be captured when appropriate.  For the week following the 
implantation, subjects will be advised to limit significant physical activity to ensure optimal 
healing at the implantation sites. 
Within the first week following implantation, subjects will return to the clinic for Visit 4 (Day 2) 
and Visit 5 (Day 5).  Clinical monitoring will be performed to identify and assess: bleeding, 
bruising, redness, localized swelling, and pain (discomfort).  Additionally, subjects will be 
monitored for potential immunological reactions to the implantation by traditional symptoms and 
signs including:  anaphylaxis, acute breathing problems (such as stridor caused by airway 
edema), angioedema, severe implantation site reactions at more than one site, diffuse and severe 
erythematous rash, diffuse and severe urticarial new onset multi-joint arthralgia or swelling.  
These events will be captured as AEs.  If the Investigator suspects the subject might be having an 
immunological reaction, the Sponsor or its designee must be contacted immediately.  Any 
additional pre- or post-operative evaluations or visits conducted beyond the protocol-specified 
study visits are at the discretion of the surgeon and/or Investigator and should be captured as an 
Unplanned Visit.   

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7.4. 
Photographs of Implantation and Explantation Sites 
Photographic images may be obtained during the study on a small group of subjects to visually 
document the anatomical implantation and explantation sites immediately before and at various 
times after the procedures.  It is expected that one or two sites will be selected to perform these 
assessments and that these assessments will occur with some or all of the subjects at the site(s).    
Training and instructions for capturing the appropriate images in a standardized manner will be 
provided to the site(s) selected to participate in this activity.  To maintain subject confidentiality, 
photographic images will be limited to the implantation and explantation sites and will not 
include any images of the subject’s facial features or any other uniquely identifiable physical 
features.  Photographs will be de-identified and may be uploaded to a central repository and used 
to refine the surgical procedure, site training, or other educational purposes related to the conduct 
of the clinical trial. 
7.5. 
Video of Implantation and Explantation Procedures 
Video images may be obtained during the study on a small group of subjects to visually 
document the implantation and explantation procedures.  It is expected that one or two sites will 
be selected to capture video of the procedure and that these assessments will occur with only 
some of the subjects at the site(s).   
To maintain subject confidentiality, video images will be limited to the implantation and 
explantation sites during the procedure and will not include any images of the subject’s facial 
features or any other uniquely identifiable physical features.  Video will be de-identified and 
uploaded to a central repository and used to refine the surgical procedure, site training, or other 
educational purposes related to the conduct of the clinical trial. 
7.6. 
Ultrasound Monitoring 
Ultrasound monitoring will be performed by trained personnel at the clinical site.  The 
ultrasound evaluation will be performed using clinical-grade ultrasound machines.  For 
consistency of results, it is recommended that the same evaluator at the site perform all of the 
ultrasound evaluations on a subject and that the same machine be used on a subject throughout 
the trial. Ultrasound monitoring will be required during the study and serves two purposes:   
1. To monitor graft performance (safety evaluation); and 
2. To pre-identify the anatomical location of the implanted units prior to an explantation 
procedure.  
These purposes are discussed in more detail below. 
 Graft performance (safety) ultrasound monitoring:  Off-target (i.e., non-
pancreatic) growth could occur inside the device.  Certain types of off-target cells 
(e.g., chondrocytes) are not limited by oxygen diffusion into the device and, 
therefore, can keep growing and expanding the device lumen.  In contrast, target 
pancreatic tissue has never been observed to expand the device lumen beyond 200-
300 m thickness.  Ultrasound imaging intervals are set such that if that were to 

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occur, lumen expansion is expected to be detectable by ultrasound monitoring well 
before a time where the growth is sufficient to rupture the device.   
Thus, ultrasound monitoring will assess the physical dimensions of the implanted 
units.  In particular, thickness of the lumen will be monitored in an attempt to identify 
excessive cell growth cell growth that could be indicative of an off-target population.  
If excessive growth is observed, the unit will be prophylactically removed and an 
appropriate level of follow-up performed. 
The ultrasound images for safety evaluations will be captured, transmitted, and 
analyzed by a third-party, central imaging core lab. 
 Identify anatomical location of implanted units prior to explantation procedure:  
Ultrasound evaluation will be performed around the time of any sentinel and/or VC-
01-250 unit explantation (pre-explant) for surgical planning purposes.  This will allow 
the explanting surgeon to minimize tissue trauma and reduce the likelihood of 
disturbing adjacent implants.   
It is possible that the “safety” ultrasound procedure may correspond with the scheduling of the 
“anatomical location” ultrasound, and these investigations can be combined into one procedure.  
In addition, there will also be “safety” ultrasounds required which do not correspond to an 
upcoming explant procedure.   
Early experiences in this study indicate the established ultrasound imaging procedure is 
successful at imaging implanted units and is appropriate for the purposes identified above.  If 
modifications to the ultrasound procedure are considered necessary based on data collected over 
the course of the trial, the sites will be notified. Further information will be available in the 
imaging core lab manual and/or study reference manual. 
7.7. 
Explantation of VC-01-20™ or Comparator Sentinel Units 
VC-01-20 or Comparator sentinel units are co-implanted with the larger therapeutic VC-01-250 
units.   
In Cohort 1, between four (4) and six (6) VC-01-20 or Comparator sentinels will be implanted.  
Of these sentinel units, up to three (3) may be Comparator sentinels.  
In Cohort 2, up to three (3) VC-01-20 sentinels will be implanted.  The number of sentinels 
implanted in Cohort 2 will be determined by the Sponsor in collaboration with the site.  The 
decision will be based on the available data from previous subjects as well as on the availability 
of anatomical space for surgical implantation.   
All sentinel units will be removed at time-points to be determined by the Sponsor (refer to the 
Schedule of Assessments - Table 1, Table 2, and Table 3).   
Early experiences in the study indicate that while under anesthesia, the sentinel and the 
surrounding tissue capsule can be explanted with traditional surgical instruments, ensuring that 
the remaining implanted units are not disturbed.  Local anesthesia is required at a minimum, with 
the use of sedation or general anesthesia at the discretion of the surgeon.  A study reference 
manual will outline the sentinel explantation procedures to be performed by appropriately-

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trained site personnel. The Sponsor or designee will provide training on the proper explantation 
technique.   
The site should provide each subject with instructions on proper wound care and evaluation after 
sentinel explanation procedure, including a reminder to contact the site if any problems occur.  
As this is a FIH study, there is the possibility that the explantation procedures and techniques 
will be modified based on the data collected on Cohort 1 or Cohort 2 subjects.  The Sponsor will 
communicate with the site surgeons to understand where improvements may be made.  Updates 
will be communicated to other sites as appropriate.  If additional training of the sites is required, 
it will be provided. 
7.8. 
Explantation of VC-01-250™ Units 
As outlined in the Schedule of Assessments (Table 1, Table 2, and Table 3), the VC-01-250™ 
units will be removed from all subjects at the end of the specified treatment period or earlier if 
the subject wishes to withdraw from the study, has a safety event which requires explant, or if 
the Sponsor/IRB/REB/DSMB/Regulatory Authorities stop the study.    
At the discretion of the Sponsor and after consultation with the site investigator, or if a unit is 
suspected to be malfunctioning or damaged, explantation of one VC-01-250 unit is allowed at 
any time post-implant for a subject.  Explant of one VC-01-250 unit may occur without requiring 
the subject to officially withdraw from the study (Section 13.6).  The up to two VC-01-250 units 
implanted in Cohort 1 subjects are expected to deliver approximately 60,000 to 90,000 islet 
equivalents (IEQ), which may not result in detectable C-peptide levels.  Although the sentinel 
units implanted in subjects are expected to behave similarly to the VC-01-250 units, an explant 
of a single VC-01-250 unit is permitted and will provide additional data on the status of graft 
function and cell performance.   
Early experiences in the study indicate that while under anesthesia, the VC-01-250 unit and the 
surrounding tissue capsule can be explanted with traditional surgical instruments, ensuring that 
the remaining implanted units are not disturbed.  Local anesthesia is required at a minimum, with 
the use of sedation or general anesthesia at the discretion of the surgeon.  A study reference 
manual will outline the sentinel explantation procedures to be performed by appropriately-
trained site personnel. The Sponsor or designee will provide training on the recommended 
explantation technique.    
The site should provide each subject with instructions on proper wound care and evaluation after 
the VC-01-250 explanation procedure, including a reminder to contact the site if any problems 
occur. 
As this is a FIH study, there is the possibility that the explantation procedures and techniques 
will be modified based on the data collected on Cohort 1 or Cohort 2 subjects.  The Sponsor will 
communicate with the site surgeons to understand where improvements may be made.  Updates 
will be communicated to other sites as appropriate.  If additional training of the sites is 
necessary, it will be provided. 

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7.9. 
Histological Assessment of Sentinel Units and VC-01-250™ Units 
All explanted VC-01-20™ and/or Comparator sentinel units and VC-01-250™ units will be placed 
in a fixative solution and immediately shipped back to ViaCyte or a designee for histologic 
assessment.  Sample storage and shipping instructions will be provided to each site.  Systematic 
histologic evaluation of the sentinel explants will help inform the team as to the expected 
performance of the larger implants (VC-01-250™ combination product) while the study is 
ongoing.  Histological assessment of the units will be performed at ViaCyte or designee and may 
include but is not limited to: 
 Survival of implanted cells via cell nuclei count through H&E staining. 
 Differentiation of PEC-01™ to endocrine cells and particularly insulin-expressing 
cells via immunohistochemical staining. 
 The host tissue inflammatory or immunological response in the implantation area(s). 
The data from this evaluation may be captured in a separate database and described in a separate 
study report.  The data may be used to optimize the implantation procedure, anatomical location 
of implants, or the perioperative care in conjunction with VC-01.  Results from these 
assessments may be compared to the Sponsor’s database of rodent devices. 
7.10. 
Blood Glucose Monitoring 
Throughout the trial, enrolled subjects will continue with concurrent exogenous insulin 
therapy as needed, and insulin requirements will be clinically managed and titrated as 
needed to maintain glycemic control throughout the study.   For purposes of this study, the 
diary entries made by the subjects (e.g., insulin doses, SMBG fingerstick values, and HE 
occurrences) are the main source of information available to investigators to assist with 
treatment decisions.   
T2DM subjects are not required to complete the study diary; therefore, treatment decisions are to 
be made based on the investigator’s judgment and local standard of care.  However, the SMBG 
supplies will be dispensed to the SSA subjects and utilized as applicable.  
Blood glucose monitoring will be performed by various methods throughout the study to ensure 
proper glucose control:  
 Laboratory tests at clinic visits (Sections 7.2 and 7.12) 
 Continuous Glucose Monitoring (CGM) data (via CGM system provided to each 
T1DM subject).   
 SMBG fingerstick via portable meter provided to each subject   
Data from each of these methods will be reported via central laboratory, study diaries, and/or 
uploaded via computer technology.  A study reference manual will outline the various logs and 
data collection portals. 
Data collected from various sources from Visit 2 (Week -3) through Visit 3 (Day 1) will 
establish the baseline characteristics of each subject’s diabetes pattern, (e.g. % time spent at 

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various blood glucose cutpoints via CGM data; SMBG fingerstick blood glucose levels, 
exogenous insulin doses, and frequency of hypoglycemic events).  
During the study, decreasing requirements for exogenous insulin are expected to be achieved 
gradually, and are estimated to begin two to three months post implantation as cells differentiate 
into mature insulin-secreting cells. General contact, phone calls, and/or unplanned visits with the 
subject between visits are encouraged to facilitate insulin adjustments and to address any 
potential safety issues.  In addition to Investigator review of fingerstick glucose values required 
per protocol, internal Sponsor review of blood glucose value data will be conducted routinely.  If 
potentially concerning trends are seen for an individual subject, the Investigator will be notified 
and follow-up with the subject will occur if necessary. 
7.10.1. 
Continuous Glucose Monitoring (CGM) 
All T1DM subjects will be provided with a Continuous Glucose Monitoring (CGM) system.  
Subjects are required to wear their Sponsor-provided CGM during the 30-day period (window of 
±seven days) prior to their scheduled clinic visits, although wearing of the CGM for the entire 
two-year study is encouraged.  
All supplies and instructions on device use will be provided.  Appropriately-qualified site 
personnel will instruct the subject on proper use and care at Visit 2 (Week -3) and as needed 
throughout the study.  All subjects will be required to use the same Sponsor-provided CGM 
device in order to participate in the trial.  The CGM device is configured to alert the subject in 
the event blood glucose values approach hypoglycemic levels. 
At Visit 2 (Week -3), if the subject is unfamiliar with CGM, site personnel will be required to 
spend adequate time to ensure the subject understands the CGM and how to operate it.  This 
training includes assisting the subject with the insertion of the sensor needle.  Having previous 
experience with CGM is not a requirement of study entry, but all subjects are required to use 
CGM during study participation. 
Data from the two weeks prior to appropriate clinic visits will be used in order to calculate the 
CGM endpoints (e.g., percent of time a subject’s blood sugar is ≥180 mg/dL, ≥250 mg/dL, or 
<40 mg/dL, ≤50 mg/dL, ≤60 mg/dL, ≤70 mg/dL).  Other endpoints using CGM data may be 
evaluated and, if so, will be described in the Statistical Analysis Plan (SAP). 
In keeping with the labeled indication of the CGM device (i.e., Dexcom Platinum G4) being used 
in this trial, CGM data should not be used by the PI for treatment decisions, such as how much 
insulin subjects should take.  The CGM system does not replace a SMBG meter.  The subject 
should be encouraged and reminded to use the blood glucose values from the SMBG meter for 
insulin dosing decisions.  The subject must record SMBG values, HE occurrence, and insulin 
dosing into the diary every day.  This diary data must be reviewed by the site for completeness 
and in determining whether insulin dosing should be modified.  Using the CGM sensor blood 
glucose readings for treatment decisions could lead to low or high blood glucose values.  The 
CGM data for this trial will be used internally for secondary and exploratory endpoints.  If CGM 
data is used at a site for an additional layer of diabetes monitoring, individual sites should 
determine how best to use available CGM data within the labeled indication. 
T2DM subjects are not required to wear a CGM system during the study.    

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7.10.2. 
Self-monitoring Blood Glucose (SMBG)  
Self-monitoring blood glucose (SMBG) supplies including a Sponsor-provided portable meter, 
test strips, lancets, control solution, and sharps containers will be provided and required for use. 
Instructions for SMBG monitoring at home via fingerstick and calibration of the portable meter 
will be provided to each subject. Recommended frequency for routine SMBG monitoring via 
fingerstick will be determined for each subject by the Investigator or designee. 
SMBG log [includes records of any hypoglycemic events and accompanying symptoms (if any), 
fingerstick blood sugar measurements] and exogenous insulin dose logs will be completed via 
study diary by T1DM subjects only. For entries in the electronic tablet diary, data will be 
available for review in near real-time by the site staff via internet portal once synchronized 
through Wi-Fi by the subject.  Based on entries made on the electronic tablet diary, e-mail alerts 
will be sent to the Investigator in the event a SHE is reported, or if the number of hypoglycemic 
events occurring within a seven (7)-day period requires further evaluation.     
SMBG must be undertaken in the event that the subject believes he/she is experiencing 
symptoms of hyperglycemia or hypoglycemia such as: hunger, headache, dizziness, light-
headedness, sweating, palpitations, tachycardia, tremulousness (shakiness), irritability, blurred 
vision, and disorientation etc., which cannot be reasonably explained by another cause (e.g., 
increased physical activity, skipped meal).  Any confirmed (i.e., SMBG of ≤70 mg/dL) or 
unconfirmed (i.e., no SMBG value available) episode of hypoglycemia must be captured by the 
subject as soon as possible on the diary.  
 For any severe hypoglycemic events (SHE) experienced between scheduled clinic 
visits, the subject must enter the data on the diary and also contact the study site to 
provide details of the event.  
T2DM subjects are not required to enter HEs on a study diary, but in the event a T2DM subject 
experiences a HE, sites should collect the details of any HEs spontaneously reported by the 
subject and record on the CRF.  If a T2DM subjects experiences a SHE, the subject must contact 
the study site to provide details of the event.  
The site may request the subject return for an unplanned visit to review the glucose values and 
determine whether or not modifications in exogenous insulin dose are necessary in order to 
reduce the occurrence of hypoglycemic events.  Investigators must review the hypoglycemic 
event information present on the diary, SMBG, glucose value trends, and exogenous insulin dose 
logs completed by the subjects at each study visit and must document this review in the subject 
source records.  Based on this information, an assessment of any symptomatic occurrence of 
hypoglycemia must be undertaken, and the Investigator or the treating physician should make 
appropriate decisions regarding current insulin therapy dose regimen. 
7.10.3. 
Definition and Classification of Hypoglycemic Events 
All SMBG values of ≤70 mg/dL must be captured by the subject in the diary as a Hypoglycemic 
Event (HE).  If a subject does not have an SMBG fingerstick value available but has symptoms 
of an HE, the HE must still be captured in the diary as an HE.   
At each clinic visit, the Investigator or designee will review the subject-completed diary 
hypoglycemic event (HE) information, SMBG values, and any other supportive information.  

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Each hypoglycemic event occurring beyond Visit 2 must be captured on a CRF and will be will 
be classified given the definitions below.  The investigator should still evaluate hypoglycemic 
events occurring between V1 and V2, but they are not captured on the CRF. 
Severe hypoglycemic event (SHE):  an event requiring assistance of another person to 
actively administer carbohydrate, glucagon, or other resuscitative actions. 
Documented symptomatic hypoglycemia:  an event accompanied by typical symptoms of 
hypoglycemia with documented plasma glucose measured at ≤70 mg/dL (3.9 mmol/L). 
Asymptomatic hypoglycemia: an event with measured plasma glucose of ≤70 mg/dL (3.9 
mmol/L) in the absence of symptoms. 
Probable symptomatic hypoglycemia: subject reports typical hypoglycemia symptoms 
but does not provide a temporally-associated SMBG value. 
In addition to the hypoglycemia levels defined above, an additional category of “pseudo-
hypoglycemia” will be noted. 
Pseudo-hypoglycemia or relative hypoglycemia: an event is reported by subject, but the 
associated SMBG value is >70 mg/dL (3.9 mmol/L). 
The frequency of these events will be captured and counted over the course of the study.  In 
addition, the Sponsor will consider defining additional exploratory hypoglycemic events using 
the CGM data.   
7.11. 
Patient-Reported Outcome Measurements 
Patient-Reported Outcome Measure (PROM) instruments will be completed for all T1DM 
subjects while in a fasted state at select study visits throughout the study as noted in the Schedule 
of Assessments.  Guidelines ensuring data quality will be optimized as suggested in the Food and 
Drug Administration (FDA) Guidance for Industry, “Patient-reported outcome measures: used in 
Medical product development to support labeling claims” [Dec 2009].  In order to minimize 
inconsistencies in the trial conduct, PROM instruments will be completed by the subject prior to 
any procedures being performed and administered via the study-provided medium.   
Training and consistent instructions to subjects for these PROM instruments will be given.  
Specifically, the subjects will complete the PROM instruments in a quiet room and should 
answer each question without interruptions and independent of other external influences (e.g., 
spouse, site personnel, Investigator).  
T2DM subjects are not required to complete the PROMs.  
7.11.1. 
Diabetes Treatment Satisfaction Questionnaire (DTSQ) 
This 8-item self-report scale assesses satisfaction with treatment for diabetes.  There are two 
versions: DTSQs (original; “status” version) and the DTSQc (“change” version).  Both versions 
were designed for use with individuals 16 years and older with type 1 or type 2 diabetes mellitus.  
Administration will take approximately five minutes.  The constructs included in these 
instruments include treatment satisfaction (six items), perceived frequency of hypoglycemia (one 
item), and perceived frequency of hyperglycemia (one item) [REF 8, 9, 10].   

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On the DTSQs, subjects will provide ratings from six (very satisfied, convenient, flexible, etc.) 
to zero (very dissatisfied, inconvenient, inflexible, etc.).  On the DTSQc, subjects will provide 
their ratings from +3 (much more satisfied now) to -3 (much less satisfied now).  Hypo- and 
hyperglycemia items will be rated from zero (none of the time) to six (most of the time).  The 
DTSQs will be administered at screening Visit 2 (Week -3), baseline Visit 3 (Day 1), Visit 12 
(Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and Visit 18 (Week 104).  The DTSQc will 
be administered at Visit 14 (Week 52), and Visit 18 (Week 104/ET).  The recall period will be no 
more than a few weeks for the DTSQs and up to 12 months for the DTSQc.   
Sample copies of the DTSQs and DTSQc are provided in Appendix A and Appendix B.  The 
actual questionnaires used in this study will be modified as appropriate (e.g., electronic format, 
protocol identifier, recall period).  The questionnaire will be reviewed and approved by the 
IRB/REB before use.  
7.11.2. 
Audit of Diabetes Dependent Quality of Life Questionnaire (ADDQoL) 
The Audit of Diabetes Dependent Quality of Life Questionnaire (ADDQoL) is an individualized 
measure of the impact of diabetes on a person’s quality of life. 
The ADDQoL will be administered at screening Visit 2 (Week -3), baseline Visit 3 (Day 1), 
Visit 12 (Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and Visit 18 (Week 104).  A 
sample copy of the ADDQoL is provided in Appendix C.  The actual questionnaire used in this 
study will be modified as appropriate (e.g., electronic format, protocol identifier, recall period). 
The questionnaire will be reviewed and approved by the IRB/REB before use. 
7.12. 
Laboratory Evaluations 
Sponsor-identified central laboratories, using a validated analytical method in compliance with 
the sponsor’s standard operating procedures (when necessary), will assay all biological samples.  
The samples will be collected at the pre-specified time-points indicated on the Schedule of 
Assessments. 
Clinical Laboratory Evaluations: 
Subjects will have routine laboratory assessments performed throughout the study.  The 
hematology assessments will include: hemoglobin, hematocrit, RBC count, platelet count, WBC 
count, total neutrophils, eosinophils, monocytes, basophils, and lymphocytes. 
The chemistry assessments will include: BUN, serum creatinine, total calcium, sodium, 
potassium, chloride, bicarbonate, magnesium, phosphate, uric acid, ALT, AST, LDH, alkaline 
phosphatase, total bilirubin (direct and indirect bilirubin reflexively measured only when total 
bilirubin is greater than the ULN), creatine phosphokinase, albumin, and total protein. 
Note: If a subject demonstrates an ALT and/or AST values of >3 x ULN during the study, the 
subject will re-test every five to seven days until the values return to <3 x ULN.  An ALT or 
AST value of >3 x ULN with total bilirubin ≥2 x ULN and alkaline phosphatase <2 x ULN 
will require re-testing every three to five days. 
The fasting serum lipid panel assessments will include: total cholesterol, HDL-C, calculated 
LDL-C (Friedwald), triglycerides, VLDL.  Non-HDL-C will be calculated as TC – HDL-C. 

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When triglycerides are >400 mg/dL, another sample will need to be collected from the subject 
and a directly measured LDL will be done. 
Other assessments occurring at various times during the trial include but are not limited to: 
serum FSH (females at screening to determine childbearing status), fasting and stimulated C-
peptide, HbA1c, fasting glucose, urine pregnancy tests (at screening and when necessary), 
screening serology for HBsAg, HCV, HIV (1&2), and renal function evaluation via MDRD 
eGFR calculation. 
Urinalysis (central lab dipstick): pH, protein, blood, ketones, leukocyte esterase, nitrites, with 
microscopy done if dipstick sample is positive for blood, nitrites, leukocytes, and/or protein.  A 
bacterial culture and sensitivity will be done if nitrites or leukocyte esterase are positive.  
Another sample will need to be collected from the subject and submitted in order to perform the 
culture and sensitivity testing.  At visits where a urine albumin/creatinine ratio is performed, the 
determination must be made on the first morning void. 
7.12.1. 
Pregnancy Tests 
Since no females of childbearing potential are allowed to enroll into the trial, a urine pregnancy 
test is administered at Visit 1, but is not included as a recurring procedure in the protocol 
Schedule of Assessments (Tables 1 and 2).  However, pregnancy tests may be completed if the 
Investigator suspects a possible pregnancy, as per request of IRB/REB, or if required by local 
regulations.  Additional information will be provided in a study reference manual. 
7.12.2. 
Immune Panel 
Blood samples for immunology-type tests will be obtained periodically throughout the trial: 
Visits 3 (Day 1), 7 (Week 4), 9 (Week 12), 12 (Week 26), 14 (Week 52), and 18/ET (Week 104).  
The immune panel of tests are listed below: 
 Humoral alloreactivity measured via HLA-PRA  
 Humoral autoimmunity measured via T1DM autoantibody titers of GADA, IAA, 
IA2A, and ZnT8  
 Cellular alloreactivity measured via mixed lymphocyte reaction (MLR) 
 Cellular autoimmunity measured via lymphocyte stimulation test (LST) 
 Cellular autoimmunity measured via Diab-Q Kit 
Blood samples will be sent to a central or third party lab with results sent to ViaCyte for possible 
inclusion in the clinical study database.  The results of these tests will help inform ViaCyte’s 
research and will not be provided to the clinical sites.  If there is enough of a blood sample 
remaining on the collected samples, other immune function related tests may be performed, but 
no additional blood collection would be required.  Fasting is not required prior to collection of 
these samples. 
The cellular allo- and autoimmunity blood samples require additional processing prior to analysis 
that must be initiated within 24 hours of the collection time.  If the additional processing cannot 
be completed onsite before being sent to the central laboratory, collection of the samples must 

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occur during afternoon hours.  If needed, the samples can be collected on a day prior to the 
remainder of the visit in order to meet the requirements, but within the protocol-allowed visit 
windows.   The baseline sample may be collected at any time between Visit 2 and Visit 3 once it 
has been determined the subject qualifies for the study.  Additional details are provided in the 
central laboratory manual.   
7.12.3. 
Reserve Blood Samples 
Additional blood samples from subjects may be collected at baseline (Visit 3) and at up to four 
additional study visits for investigational assessment of biomarkers that could be associated with 
the cellular viability and durability of the implanted VC-01 product.    The number of biomarkers 
assessed will be limited by the amount of sample available, but will not include any genetic 
testing.  If the additional blood samples are collected, as much as 3 mL of blood could be 
collected at each time point.  Results of these tests may not be reported to the site during the 
course of the study.  Additional details of these tests will be provided in a separate laboratory 
manual. 
7.12.4. 
Specimen Preparation, Handling, and Shipping 
Details regarding the laboratory specimen preparation, handling, storage, and shipping 
procedures will be outlined in a separate laboratory reference manual. 
7.12.5. 
Blood Volumes 
For T1DM subjects, total blood collection volumes from visits requiring lab assessments are not 
planned to be greater than 750 mL over the course of the 2-year trial.  Of the nineteen (19) clinic 
visits, there are four (4) visits where blood volumes are estimated to be up to approximately 95 
mL: Visit 2 (Week -3), Visit 9 (Week 12), Visit 12 (Week 26), and Visit 14 (Week 52).  Other 
visits, the blood volume required ranges from 0 mL to 55 mL.   
If the reserve blood samples (Section 7.12.3) are collected, this would result in up to an 
additional 15 mL of blood collected over the 2-year trial. 
For T2DM subjects there are fewer study visits and laboratory tests required. Total blood 
collection volumes from visits requiring lab assessments are not planned to be greater than 190 
mL over the course of the 6-month trial.  Of the 13 clinic visits, there are five (5) visits where 
blood volumes are estimated to be up to approximately 35 mL: Visit 1 (Week -4), Visit 3 (Day 
1), Visit 7 (Week 4), Visit 8 (Week 8), and Visit 12 (Week 26).  For other visits, the blood 
volume required ranges from 0 mL to 10 mL.   
For all subjects, as noted in the Schedule of Assessments, blood collections are not planned to 
occur more frequently than once per week unless there is a need for an unplanned (safety) visit. 
7.13. 
Simplified Oral Glucose Challenge Test 
All subjects will be tested for evidence of a detectable (>0.2 ng/mL), stimulated C-peptide level 
via a simplified oral glucose challenge test at Visit 1.  After Implantation Visit 3, the simplified 
oral glucose challenge test will be conducted at Visit 8 (Week 8), Visit 9 (Week 12), Visit 10 

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(Week 16), Visit 11 (Week 20), Visit 13 (Week 39), and Visit 16 (Week 78) until a measurable 
C-peptide result (>0.1 ng/mL) is obtained.   
For T1DM subjects, once a measurable C-peptide level is obtained, no additional simplified oral 
glucose challenge tests are required and the subject should instead follow the schedule for 
completion of the 2-hour MMTT (Section 7.2).   
T2DM subjects will complete the simplified oral glucose challenge test regardless of C-peptide 
results. 
After all fasting blood and urine samples required at the visit have been collected, at time = 0, the 
subject will then be administered a standard meal consisting of one nutrition drink (Boost® Hi-
Protein drink, 6 mL/kg body weight to a maximum of 360 mL).  The entire amount of Boost® 
must be ingested within 15 minutes.  One blood sample for C-peptide is then collected at any 
time between 30 to 60 minutes after the start of the Boost® meal test.   
8. 
SAFETY REPORTING 
The Investigator is to report all directly observed AEs, all AEs spontaneously reported, or 
pregnancies by the study subject.  In addition, each study subject will be questioned about AEs 
and pregnancies (if applicable) at each clinic visit.  
8.1. 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject 
administered a product or medical device.  Adverse events need not necessarily have a causal 
relationship with the treatment or usage.  
Examples of AEs include, but are not limited to: 
 Abnormal test findings; 
 Clinically significant symptoms and signs (changes from baseline status); 
 Clinically significant changes in physical examination findings; 
 Hypersensitivity; 
 Progression/worsening of underlying disease (includes worsening diabetes); 
All observed or volunteered AEs regardless of suspected causal relationship to the 
investigational product will be reported as described in the following sections. 
For all AEs, the Investigator must pursue and obtain information adequate both to determine the 
outcome of the AE and to assess whether it meets the criteria for classification as a serious 
adverse event (SAE) requiring immediate notification to ViaCyte or its designated representative 
and the site’s IRB/REB. For all AEs, sufficient information should be obtained by the 
Investigator to determine the causality of the AE. The Investigator is required to assess causality. 
Follow-up by the Investigator may be required until the event or its sequelae resolve or stabilize 
at a level acceptable to the Investigator, and ViaCyte concurs with that assessment.  

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As part of ongoing safety reviews conducted by the Sponsor, any non-serious AE that is 
determined by the Sponsor to be serious will be reported by the Sponsor as an SAE. To assist in 
the determination of case seriousness, further information may be requested from the 
Investigator to provide clarity and understanding of the event in the context of the clinical trial. 
As required on the AE CRFs, the Investigator will use the National Cancer Institute (NCI) – 
Common Terminology Criteria for Adverse Event (CTCAE) guidelines to describe the 
maximum intensity of the AE.  For purposes of consistency, these intensity grades are defined as 
follows: 
 
MILD 
Asymptomatic, or mild symptoms, clinical or diagnostic observations noted; 
intervention not indicated 
MODERATE 
Local or noninvasive intervention indicated 
SEVERE 
Medically significant but not immediately life threatening, hospitalization or 
prolonged hospitalization. 
LIFE-THREATENING 
Life-threatening consequences, urgent intervention indicated 
DEATH 
Death related to AE 
 
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (medically significant) but would 
not be classified as serious unless it met one of the criteria for SAEs (See Section 8.2).  
In addition, if the Investigator determines an SAE is associated with study procedures, the 
Investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting requirements, 
if applicable.  
All AEs will be reported on the AE page(s) of the CRF after Visit 2.  It should be noted that the 
form for collection of SAE information may not be the same as the AE CRF.  Where the same 
data are collected, the forms must be completed in a consistent manner. AEs should be reported 
using concise medical terminology. 
8.1.1. 
Causality Assessment of Adverse Events 
The Investigator’s assessment of causality must be provided for all AEs (serious and non-
serious).  The Investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that the investigational product itself caused or contributed to an AE.   
If the Investigator’s final determination of causality is unknown, and the Investigator does not 
know whether or not the investigational product or surgical procedure caused the event, then the 
event will be handled as “related to investigational product” for reporting purposes.  If the 
Investigator’s causality assessment is “unknown but not related to investigational product”, this 
should be clearly documented on study records.  

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Relationship of an AE to the implanted units, the surgical implantation procedure and/or the 
explantation procedure will be assessed as follows: 
Not related [unrelated or unlikely related]:  A clinical event including laboratory test 
abnormalities without a temporal relationship to the investigational product exposure or the 
surgical procedures which makes a causal relationship improbable, and/or in which other drugs, 
chemicals, or underlying disease provides plausible explanations. 
Possibly related:  A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to exposure of the investigational product or the surgical procedures, but which could 
also be explained by concurrent disease or other drugs or chemicals.  
Probably related:  A clinical event, including laboratory test abnormality, with a reasonable 
time sequence to the investigational product exposure or surgical procedures, unlikely to be 
attributed to concurrent disease or other drugs or chemicals, and which follows a clinically 
reasonable response. 
8.1.2. 
Expected Adverse Reactions 
As this is the first in human study, there are no definitive expected adverse reactions to this 
product, only hypothetical risks.   
There are expected adverse reactions from the surgical implantation and explantation of the 
sentinels and VC-01-250 units and these are: localized procedural tenderness, pain, bleeding, 
itching, swelling, redness, and possible infection at the implant and explant sites. 
Especially in Cohort 2 when the implanted cells are expected to begin to exert their physiologic 
action, there may be an increase in the number of hypoglycemic events noted before exogenous 
insulin doses are decreased.  All events, whether they are expected or unexpected, will be 
captured as AEs and, if appropriate, SAEs. 
8.1.3. 
Suspected, Unexpected Serious Adverse Reactions (SUSAR) 
A SUSAR is a serious adverse reaction which is thought to be causally related to the 
investigational product or procedure and which is unexpected to occur.  Reporting of SUSAR to 
the Sponsor or its designee, to the investigative sites, to the IRB/REBs and to the Regulatory 
Authorities during the trial is mandatory. 
Because of the limited shelf-life of the investigational product, the results of continuous 14-day 
sterility testing of VC-01 are not available until after implantation occurs.  In the unexpected 
event of positive culture results, the Sponsor will notify the PI, who will then notify the 
applicable subject.   The Sponsor or designee will initiate further testing of the positive sample to 
identify the microorganism and conduct a root-cause analysis.  The PI and Sponsor will evaluate 
any additional actions required to appropriately monitor the subject based on the results of the 
sample.  If the medical condition of the patient is impacted as a consequence of the 
microorganism causing the positive sterility results, the event should be reported as a SUSAR 
within 15 days.   

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8.1.4. 
Unanticipated Problems 
If there are unanticipated problems with the implantation and/or explantation of the units, these 
will be captured and reported to the Sponsor or designee so that further evaluation can be 
performed.  As appropriate, unanticipated problems will be communicated to each site and to 
Regulatory Authorities by the Sponsor as appropriate.  Each site will be responsible for reporting 
to the IRB/REB as appropriate. 
8.1.5. 
Procedures to Be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
AE are as follows: 
 Test result is associated with accompanying symptoms, and/or  
 Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
 Test result leads to discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy, and/or 
 Test result is considered to be an AE by the Investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
8.1.6. 
Adverse Events of Special Interest 
Unexpected or premature explantation of sentinel or VC-01-250 units due to an AE are 
considered AEs of special interest.  Also, subject-reported HEs will also be considered AEs of 
special interest.  There may be additional data collected on these events.   
Further instruction will be outlined in a study reference manual. 
8.2. 
Serious Adverse Events (SAE) 
An SAE is any untoward medical occurrence that: 
 Results in death; 
 Is life-threatening (immediate risk of death); 
 Requires in-patient hospitalization or prolongation of existing hospitalization; 
 Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
 Results in congenital anomaly/birth defect; 
 Constitutes an Important Medical Event. 

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Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize the 
subject or may require intervention to prevent one of the other AE outcomes, the important 
medical event should be reported as serious. 
Based on the definition above, severe hypoglycemic events (SHE) may or may not be reported as 
SAEs and will be left to the PI’s discretion; however, they will need to be recorded on the 
hypoglycemic event (HE) CRF.  
AEs reported from studies associated with hospitalization or prolongations of hospitalization are 
considered serious.  Any initial admission (even if less than 24 hours) to a healthcare facility 
meets these criteria.  Admission also includes transfer within the hospital to an acute/intensive 
care unit (e.g., from the psychiatric wing to a medical floor, medical floor to a coronary care unit, 
neurological floor to a tuberculosis unit). 
Hospitalization does not include the following: 
 Rehabilitation facilities; 
 Hospice facilities; 
 Respite care (e.g., caregiver relief); 
 Skilled nursing facilities; 
 Nursing homes; 
 Routine emergency room visits; 
 Same day surgeries (as outpatient/same day/ambulatory procedures). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not in itself an SAE.  Examples include: 
 Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (e.g., for 
work-up of persistent pre-treatment lab abnormality); 
 Social admission (e.g., subject has no place to sleep); 
 Administrative admission (e.g., for yearly physical exam); 
 Protocol-specified admission during a study (e.g., for a procedure required by the 
study protocol); 
 Optional admission not associated with a precipitating clinical AE (e.g., for elective 
cosmetic surgery); 
 Hospitalization for observation without a medical AE; 
 Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or the individual subject. 

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Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not be 
reported as AEs.  However, the medical condition for which the procedure was performed should 
be reported if it meets the definition of an AE.  For example, an acute appendicitis that begins 
during the AE reporting period should be reported as the AE, and the resulting appendectomy 
should be recorded as treatment of the AE.  
8.2.1. 
SAE Reporting Procedures 
If an SAE occurs, ViaCyte or designee will be notified within 24 hours of Investigator awareness 
of the event.  
In particular, if the SAE is fatal or life-threatening, notification to ViaCyte or designee must be 
made immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as well 
as to the initial and follow-up reporting of exposure during pregnancy and exposure via 
breastfeeding cases. 
In the rare event that the Investigator does not become aware of the occurrence of an SAE 
immediately (e.g., if an outpatient study subject initially seeks treatment elsewhere), the 
Investigator is to report the event within 24 hours after learning of it and document the time of 
his/her first awareness of the AE. 
For all SAEs, the Investigator is obligated to pursue and provide information to ViaCyte in 
accordance with the timeframes for reporting specified above.  In addition, an Investigator may 
be requested by ViaCyte to obtain specific additional follow-up information in an expedited 
fashion.  This information collected for SAEs is more detailed than that captured on the AE CRF.  
In general, this will include a description of the AE in sufficient detail to allow for a complete 
medical assessment of the case and independent determination of possible causality.  Information 
on other possible causes of the event, such as concomitant medications and illnesses must be 
provided.  In the case of a subject death, a summary of available autopsy findings must be 
submitted as soon as possible to ViaCyte or its designated representative. 
8.2.2. 
Sponsor Reporting Requirements to Regulatory Authorities  
Adverse event reporting, including SUSARs, will be carried out in accordance with applicable 
local regulations. 
8.3. 
Reporting of Pregnancy 
For investigational products, an exposure during pregnancy [also referred to as Exposure in 
Utero (EIU)] occurs if an enrolled female subject becomes, or is found to be, pregnant while in 
the study. In addition, if a male subject reports that his partner has become pregnant while he has 
had the VC-01 units implanted, this will also be captured as an EIU.  Although women of 
childbearing potential are excluded from participating in this trial, the reporting procedures 
outlined in this section are provided as a precautionary measure.   
Pregnancy itself is not an AE. However, adverse consequences of pregnancy should be reported 
as an AE/SAE. 

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If a study subject or a study subject’s partner becomes or is found to be pregnant during the 
study, the Investigator must submit this information to ViaCyte or designee on an EIU Form.  
This must be done within 24 hours of awareness of the event.  The information submitted should 
include the anticipated date of delivery (see below for information related to termination of 
pregnancy).  All confirmed EIU cases and follow-up information will be reported in a Pregnancy 
Registry. 
Follow-up is conducted to obtain pregnancy outcome information for all EIU reports with an 
unknown outcome.  The Investigator will follow the pregnancy until completion (or until 
pregnancy termination) and notify ViaCyte of the outcome as a follow-up to the initial EIU 
Form.  In the case of a live birth, the structural integrity of the neonate can be assessed at the 
time of birth.  In the event of a termination, the reason(s) for termination should be specified, 
and, if clinically possible, the structural integrity of the terminated fetus should be assessed by 
gross visual inspection (unless pre-procedure test findings are conclusive for a congenital 
anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (i.e., ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live 
born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the Investigator 
should follow the procedures for reporting SAEs. 
Additional information about pregnancy outcomes that are reported as SAEs follows: 
 Spontaneous abortion includes miscarriage and missed abortion; 
 Neonatal deaths that occur within one month of birth should be reported, without 
regard to causality, as SAEs.  In addition, infant deaths after one month should be 
reported as an SAE when the Investigator assesses the infant death as related or 
possible related to exposure to investigational product. 
Additional information regarding the exposure during pregnancy may be requested by the 
Investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis (e.g., 
follow-up on preterm infants to identify developmental delays).  In the case of paternal exposure, 
the investigator will provide the study subject with a Pregnant Partner Release of Information 
Form to deliver to his partner.  The Investigator must document on the EIU Form that the subject 
was given this letter to provide to his partner. 
8.4. 
Reporting Period 
For SAEs, including pregnancy reports, the active reporting period to the Sponsor or its 
designated representatives begin from the time that the subject provides informed consent 
through and including 28 days after explantation of all of the investigational product units. SAEs 
occurring to a subject after the active reporting period has ended should be reported to the 
Sponsor if the investigator becomes aware of them; at a minimum, all SAEs that the investigator 
believes have at least a reasonable possibility of being related to the investigational product are 
to be reported to the Sponsor.   

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AEs should be recorded on the CRF from Visit 2 (Week -3) through the last subject visit.  At the 
conclusion of the trial, any ongoing AEs will be followed up on 28 days after the explantation 
procedure.   
The reporting period for AEs/SAEs will overlap with the timing of the subject’s participation in 
the mandatory 3-year follow-up study.  Further details on the reporting of AEs spanning this 
VC01-101 protocol and the long-term follow-up protocol VC01-201 will be outlined in the 
separate follow-up protocol.    
During the study, all subjects will have follow-up questions regarding their ongoing AEs at 
subsequent clinic visits.  Depending on the reported event, there may be the need for the 
Investigator or designee to follow-up on AEs by phone with the study subject.   
8.5. 
Data Safety Monitoring Board (DSMB) 
An independent Data Safety Monitoring Board (DSMB) will meet at specified times throughout 
the study to review the accumulation of data.  The DSMB will consist of at least 3 members, 
including a statistician.  No Investigator involved in the trial or anyone connected to the Sponsor 
or participating vendors such as a CRO may be a member of the DSMB.  Based on the review of 
the safety data, the DSMB may make recommendations regarding the conduct of the study.  
These may include, but are not limited to, amending safety-monitoring procedures, modifying 
the protocol or consent, terminating the study, or continuing the study as designed.  The 
discussions and decisions of the DSMB will be summarized in written reports and provided to 
the Sponsor or designee.  Where necessary, summary DSMB reports may be distributed to 
participating sites for submission to IRB/REBs.  A separate DSMB Charter will direct the 
activities of the DSMB.   
The approximate timing of DSMB meetings are noted below: 
 After a minimum of three (and up to approximately 30) subjects from Cohort 1 have 
reached the Week 4 clinic visit and the results are available, the DSMB will meet.  
The available cumulative data collected in all subjects from Cohort 1 up until that 
time will be evaluated by the DSMB.  The DSMB will make a recommendation based 
upon these findings to trigger the start of Cohort 2.  The DSMB will not meet 
regularly during Cohort 1 unless there is a related AE that requires an independent 
DSMB review. 
 At approximately 12-week intervals during Cohort 2’s enrollment phase. 
 Once the last subject has been enrolled in Cohort 2, the DSMB will meet 
approximately every six months until the last subject last visit has occurred. 
Meetings of the DSMB may be added based on data review or by request.   
8.6. 
Study Stopping Rules 
If any of the following safety events are noted to occur in the study, an ad-hoc meeting of the 
DSMB will be requested.  The DSMB will review the data and may recommend stopping the 
study for any of the following:   

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1. Two or more subjects have pronounced immune responses to the VC-01 combination 
product.  
2. Two or more subjects experiencing an National Cancer Institute’s Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) Grade 3 treatment emergent adverse event 
(TEAE) in the same Medical Dictionary for Regulatory Activities (MedDRA) system 
organ class (SOC) and preferred term (PT) considered to be possibly or probably related 
to the investigational product.  TEAE is defined as an AE that starts on or after the date 
of implant surgery. 
3. After a minimum of eight weeks post-implantation, there are two or more subjects who 
each experience two or more Severe Hypoglycemic Events (SHE) over a 6-month period 
unrelated to anything other than the VC-01-250 combination product.  This also assumes 
that the SHE occurred despite reasonable reductions in the exogenous insulin 
requirements and appropriate dietary adjustments.   
4. Two or more subjects develop serious AEs related to the implantation of the sentinels or 
therapeutic units; examples of such events are noted below:  
a. Development of an off-target cell growth (i.e., teratoma) within the unit which is 
noted on ultrasound and confirmed by pathologist.  
b. A related, severe, persistent, inflammatory response that does not resolve (e.g., severe 
site reactions, urticaria, erythematous rash, anaphylaxis, acute respiratory 
insufficiency, swelling). 
5. Two or more subjects have an unexplained graft malfunction requiring explant. 
In addition to the safety events noted above, the Sponsor may also decide to terminate the study 
for other safety or efficacy reasons.  In the event that the study is terminated, all subjects will 
have their VC-01-250 units and sentinel units explanted and examined histologically, and all 
subjects will be followed for 3 years post-explant in a follow-up study (VC01-201). 
In addition to these events, the DSMB will consider whether to recommend temporarily delaying 
enrollment in the trial for events considered by the Investigator to be related to the VC-01 
combination product.  The DSMB may also recommend that treatment continue for a shorter 
duration (i.e., less than the planned two years) or with a fewer number of implanted units. The 
DSMB may also recommend that the Sponsor close the study at any time in response to any 
legitimate safety concerns.  The Sponsor will communicate DSMB recommendations to each site 
in a timely fashion.  Each site’s IRB/REB will make the ultimate decision to delay enrollment, 
modify treatment duration, or stop the study based on DSMB recommendations. 
9. 
CLINICAL MONITORING 
Routine monitoring of investigative sites by the Sponsor or designee will be done throughout the 
trial.  The purpose of these monitoring visits is to inspect the facilities and various records of the 
trial.  
The study monitor is responsible for inspecting electronic and/or online case report forms 
(CRFs) at regular intervals throughout the study to verify adherence to the protocol.  During site 

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visits, the monitors will review source documents to confirm that the data recorded on CRFs are 
accurate.  The monitor will ensure completeness and accuracy of the data and adherence to local 
regulations on the conduct of clinical research.  The Investigator and institution will allow study 
monitors direct access to source documents to perform this verification. The Investigator and site 
staff agree to cooperate with the monitor to ensure that problems detected are appropriately 
addressed and resolved. 
An associated monitoring plan will outline items to be monitored and the frequency of 
monitoring.   
It is important that the Investigator(s) and relevant site personnel are available during the 
monitoring visits and possible audits or inspections by the Sponsor, designee, or Regulatory 
Authorities and that sufficient time is devoted to the process.  
10. 
STATISTICAL CONSIDERATIONS 
Methodology for the summarization and analysis of the data collected in this trial are given here 
and further detailed in a Statistical Analysis Plan (SAP), which will be maintained by ViaCyte.  
The SAP will be written and approved prior to the last subject in Cohort 2 passing the Week 26 
visit, since this time-point will trigger a DSMB and Sponsor review of the accumulated efficacy 
and safety data.  
The study SAP may modify what is outlined in the protocol; however, any major modifications 
of the endpoints or their analyses will be reflected in a protocol amendment. 
The phrase “treatment group” is used in this section to denote the number of initially implanted 
VC-01-250 units.  If a subject has a VC-01-250 unit explanted for any reason and remains in the 
study, then he/she will be included in the treatment group that is described by the number of VC-
01-250 units originally implanted.  If no VC-01-250 units are implanted, but sentinel units are 
implanted, then the subject will be included in the “0 implanted VC-01-250 units” treatment 
group.   
All data from Cohort 1 T2DM subjects will be summarized separately from the T1DM 
subjects.  As such, all information below pertains only to Cohort 1 T1DM and Cohort 2 (all 
T1DM) subjects. 
10.1. 
Study Hypotheses 
As this is a first-in-human study, there are no statistical hypotheses being tested.   
10.2. 
Sample Size Considerations 
At least three (3) and up to approximately thirty (30) T1DM subjects will be enrolled into Cohort 
1.  Thirty-six (36) to thirty-nine (39) subjects will be enrolled into Cohort 2, for a total 
enrollment between 39 and 69 T1DM subjects in both cohorts.  Up to five (5) T2DM subjects 
may be enrolled as part of Cohort 1; this gives a total study enrollment up to 69 subjects. 
A sample size of 36 subjects in Cohort 2 will provide more than 80% power, and a sample size 
of 69 subjects will provide more than 95% power to detect a mean change from baseline to Week 

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26 in C-peptide AUC0-4h of 3.0 ng x hour/mL following an MMTT, assuming a standard 
deviation of 6.0.  Other assumptions include a two-sided test with significance level of 0.05.  
If the minimal level of detection for C-peptide is 0.20 ng/mL, this would give an AUC of 0.8 ng 
x hour/mL for the 4-hour MMTT.  The same sample sizes (36 and 69) provide the same power 
(more than 80% and more than 95%, respectively) to detect a change from baseline to Week 26 
in C-peptide AUC0-4h of 0.8 ng x hour/mL following an MMTT, assuming a standard deviation 
of 1.6.  
For the 2-hour MMTT, sample sizes of 36 and 69 would provide more than 80% and more than 
95% percent power to detect a change from baseline to Week 26 in C-peptide AUC0-2h of 0.4 ng 
x hour/mL following a MMTT (if the minimal level of detection for C-peptide is 0.20 ng/mL), 
assuming a standard deviation of 0.8.     
There is no statistical analysis being conducted on data from T2DM subjects enrolled in the 
study.  Therefore, no sample size assumptions are needed for the T2DM subjects.  Note also that 
the data from the T2DM subjects will be summarized separately from that for the T1DM 
subjects.    
10.3. 
Interim Analysis 
No decision-making interim analyses (e.g., for early stopping for efficacy or futility, or for 
modification to the planned enrollment) are planned.  A descriptive analysis may be produced 
when all subjects reach their Week 26 visit to support regulatory discussions.  This report, if 
produced, will summarize key safety and efficacy endpoints for these subjects. 
10.3.1. 
Safety Review 
To help assess specific safety events in this FIH study and/or to evaluate the implantation and 
explantation techniques, the Sponsor or designee, Medical Monitor, and site surgeon(s) and/or 
Investigator(s) will maintain close communication during Cohort 1. 
There will be an independent DSMB.  Further information about the DSMB may be found in 
Section 8.5 of this protocol as well as the DSMB Charter, including specific descriptions of the 
scope of the members' responsibilities and the processes and definitions used to review and 
assess specific safety events.  
Additional safety event adjudication committees may be established as appropriate. As described 
above, individual committee charters will provide specific descriptions of the scope of 
responsibilities and the processes and definitions used to review and assess specific safety events 
and to trigger the start of Cohort 2 enrollment.  
10.3.2. 
Internal Efficacy and Safety Review 
After the last subject in Cohort 2 passes Visit 12 (Week 26), cumulative data from all Cohort 1 
and Cohort 2 subjects will be assembled and sent to the DSMB and Sponsor for review.  If the 
Sponsor believes the efficacy data appear robust, and the DSMB believes the safety data are 
appropriate, the Sponsor may choose to proceed to an End-of-Phase 2 (EoP2) meeting with the 
FDA to discuss next steps. 

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10.4. 
Analysis Plan 
The Analysis Plan detailed below pertains only to the T1DM subjects (T1DM subjects in Cohort 
1, and all subjects in Cohort 2).  The T2DM subjects in Cohort 1 will be summarized separately 
from the T1DM subjects, and will have their own Analysis Plan. 
10.4.1. 
Analysis Populations 
The Full Analysis Set (FAS) is the intent-to-treat (ITT) set of subjects.  This set is defined as all 
T1DM subjects who were enrolled into the study and received implantation of at least one VC-
01-250 or sentinel unit on Study Day 1.  All efficacy summaries/analyses will be performed on 
the FAS.  Subjects will be summarized by treatment group.  
The Safety Analysis Set (SAS) will include all T1DM subjects who were enrolled into the study 
and in whom an implant surgery was attempted, regardless if any VC-01-250 units or sentinel-
sized units were actually implanted.  This includes all subjects in both Cohort 1 and Cohort 2.  
The SAS will be used for safety summaries. 
10.4.2. 
Demographic and Subject Characteristics 
Demographic information and subject characteristics such as gender, race, age, and baseline vital 
signs will be summarized.  Pertinent medical history will also be summarized. 
10.4.3. 
Primary Safety Analysis 
Unless otherwise specified, the SAS (both Cohort 1 and Cohort 2 T1DM subjects who meet the 
SAS criteria) will be used for the primary safety summarizations.  Adverse events and SAEs will 
be summarized by system organ class (SOC), by severity, and by relationship.  This will be done 
by treatment group and overall.  The summarization of AEs will focus on only those events that 
are TEAEs, but the AE listings will include all reported AEs regardless of when they started. 
Other safety data, such as vital signs and clinical laboratory data will be summarized by study 
visit and treatment group.  Where appropriate, change from baseline in safety data will also be 
summarized in a similar manner.   
The number of subjects undergoing a premature VC-01-250 unit explant will be provided in a 
listing which includes the reason for explantation (i.e., safety issue, malfunction, damaged, 
planned explant, etc). 
10.4.4. 
Primary Efficacy Analysis 
Change from baseline in C-peptide AUC0-4h following an MMTT at Week 26 will be analyzed 
using analysis of covariance (ANCOVA), with treatment group as a factor and baseline C-
peptide AUC0-4h as a covariate.  The FAS (both Cohort 1 and Cohort 2 T1DM subjects who meet 
the FAS criteria) will be used to analyze the primary efficacy endpoint.  The output from the 
ANCOVA will include the least squares mean (LSM) and standard error (SE) for each treatment 
group.   

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10.4.5. 
Secondary Analyses 
Each of the secondary efficacy endpoints will be analyzed using an α = 0.05 level of 
significance.  Given the large number of secondary efficacy endpoints, the p-values for these 
endpoints will be considered descriptive. 
Unless otherwise specified, the FAS (both Cohort 1 and Cohort 2 T1DM subjects who meet the 
FAS criteria) will be used to analyze the secondary efficacy endpoints.  Change from baseline in 
C-peptide AUC0-4h following an MMTT at Weeks 52 and 104 and change from baseline in C-
peptide AUC0-2h following an MMTT at Weeks 8, 12, 16, 20, 26, 39, 52, 78, and 104 will be 
analyzed in a similar manner to the ANCOVA performed for change from baseline in C-peptide 
AUC0-4h at Week 26, with the relevant baseline as the covariate.  For subjects who continue to 
have an immeasurable C-peptide (<0.1 ng/mL) as determined by the simplified oral glucose 
challenge test, the AUC of the respective 2-hour MMTT will be set to 0.   
Change from baseline in average daily insulin dose in the seven days preceding clinic visits at 
Weeks 26, 52, 78, and 104, change from baseline in frequency of hypoglycemic events at Weeks 
26, 52, 78, and 104, and change from baseline to Weeks 26, 52, 78, and 104, in PROM scores 
will be analyzed using ANCOVA, with treatment group as a factor and the relevant baseline as a 
covariate. 
Time to onset of biological response of C-peptide following MMTT will be assessed using 
Kaplan-Meier (KM) curves, with the p-value from the logrank test also provided. 
The percent of subjects who achieve exogenous insulin independence and the percent of subjects 
who achieve a 50% reduction in average weekly exogenous insulin dose at Weeks 12, 20, 26, 39, 
52, 78, and 104 will each be analyzed using Fisher’s exact test.  The number and percent of 
subjects in each treatment group and the p-value from the Fisher’s test at each time-point will be 
provided for exogenous insulin independence and for 50% reduction in average weekly 
exogenous insulin dose. 
Unless otherwise specified, the SAS (both Cohort 1 and Cohort 2 T1DM subjects who meet the 
SAS criteria) will be used to summarize secondary safety endpoints.  For the secondary safety 
endpoint of immune response as measured by serum immunoglobulin and hematological assays, 
any subject who appears to be having an immune response will have all relevant data described 
in a clinical narrative.  In addition, data of interest from the assays may be summarized by 
treatment group and overall. 
Changes in physical examinations will be summarized by treatment group and overall.  Non-
diabetic concomitant medications will also be summarized by treatment group and overall.  
Finally, implantation site assessments will be summarized at each time-point post-implantation 
and each visit thereafter.  For each site assessment symptom, the number of subjects with the 
symptom at that time-point will be summarized by treatment group and overall. 

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11. 
SOURCE 
DOCUMENTS 
AND 
ACCESS 
TO 
SOURCE 
DATA/DOCUMENTS 
In compliance with ICH GCP guidelines, it is required that the Investigator and institution permit 
authorized representatives of the Sponsor or designee, regulatory agency(s), and the IRB or 
Canadian Research Ethics Board (REB) direct access to review the subject’s original medical 
records for verification of study-related procedures and data.  Direct access includes examining, 
analyzing, verifying, and/or reproducing any records and reports that are important for the 
evaluation of the study.   
12. 
SPONSOR AUDITS AND INSPECTIONS BY REGULATORY 
AGENCIES 
For the purpose of ensuring compliance with the Clinical Trial Protocol, Good Clinical Practice 
(GCPs) and applicable regulatory requirements, the Investigator and Institution should permit 
formal auditing by or on the behalf of the Sponsor, companies working with the Sponsor, and 
inspection by applicable regulatory authorities.  The study site may be subject to review by their 
IRB/REB.  Inspection of the site’s facilities and review of study-related records may occur for 
any reason. 
The Investigator and site staff agree to allow the auditors/inspectors to have direct access to 
source documents and study records for review, being understood that the personnel is bound by 
professional secrecy.  The Investigator and site staff will make every effort to help with the 
performance of the audits and inspections, giving access to all necessary facilities, data and 
documents.  It is important that the Investigator and all relevant personnel are available during 
the audits or inspections and that sufficient time is devoted to the process.  
If the Investigator is notified of a future inspection by regulatory authorities, s/he will inform the 
Sponsor or designee and authorize the Sponsor to participate in this inspection.  The Investigator 
will immediately communicate to the Sponsor any results and/or information arising from the 
inspections by the regulatory authorities. 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1. 
Ethical Standard 
The study will be conducted in accordance with legal and regulatory requirements, as well as the 
general principles set forth in the International Ethical Guidelines for Biomedical Research 
Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), 
Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World Medical Association 
1996 & 2008).  
13.2. 
Institutional Review Board (IRB) or Research Ethics Board (REB) 
An IRB/REB must be constituted according to applicable requirements for each participating 
location.  

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It is the responsibility of the Investigator to have prospective, documented written approval of 
the study protocol, protocol amendments, informed consent documents, and other relevant 
documents, e.g., recruitment advertisements, if applicable, from the IRB/REB. All 
correspondence with the IRB/REB should be retained in the Investigator File. Copies of 
IRB/REB approvals should be forwarded to the Sponsor or designee. 
The Institution shall have no ability to alter, amend or modify the protocol. The only 
circumstance in which an amendment may be initiated without IRB/REB and Sponsor approval 
is where the change is necessary to eliminate apparent immediate hazards to the subjects. In that 
event, the Investigator must notify the IRB/REB and Sponsor in writing immediately after the 
implementation. 
13.3. 
Informed Consent Process 
The Investigator, or a person designated by the Investigator, will obtain written informed consent 
from each subject before any study-specific activity is performed. The Investigator will retain the 
original of each subject’s signed consent document and any amendments to the consent 
document.  A copy of the signed consent form will be provided to the participant.  
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. 
The informed consent document(s) used during the informed consent process must be reviewed 
and approved by the Sponsor (prior to use), approved by the IRB/REB, and available for 
inspection. The Investigator must ensure that each study subject is fully informed about the 
nature and objectives of the study and possible risks associated with participation. 
13.4. 
Exclusion of Women, Minorities, and Children (Special Populations) 
Children will not be included in this trial.  Each site will be encouraged to employ specific 
efforts to attract appropriate minority subjects and women of non-childbearing potential.  
However, women of childbearing potential will not be allowed to enroll since this is a first-in-
human trial and the fetal effects are not known. 
13.5. 
Subject Confidentiality 
All data will be coded by number to protect confidentiality of subjects 
Case Report Forms and other documents submitted to the sponsor should identify the subject by 
number only.  Documents that are not for submission to Sponsor (e.g., source documents) should 
be kept in strict confidence by the Investigator.  See also Section 11. 
13.6. 
Reasons for Withdrawal 
Investigators will make reasonable efforts to keep enrolled subjects in the study.  However, if a 
subject is removed from treatment, a termination visit must be performed.  This would generally 
include all procedures outlined in Visit 18 (Week 104) as well as the procedures outlined in 
follow-up Visit 19 (Week 105).  Adverse events should be followed until their resolution.   

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Subjects may withdraw from the trial at any time at their own request, or they may be withdrawn 
at any time at the discretion of the PI or Sponsor for safety or behavioral reasons.   
There are subject-specific criteria and product-related criterion that will necessitate withdrawal 
from the study. 
 After a minimum of eight weeks post-implantation, the subject experiences three or 
more Severe Hypoglycemic Events (SHE) over a six-month period unrelated to 
anything other than VC-01.  This also assumes that the SHE occurred despite 
reasonable reductions in the exogenous insulin requirements and appropriate dietary 
adjustments. 
 Subject has a new onset, off-target cell growth within the unit confirmed by a board-
certified pathologist as a teratoma and is considered related to VC-01. 
 Subject appears to mount an immune/inflammatory response that decreases or 
abolishes the performance of the graft and/or puts the subject at risk for immune 
reaction AEs.  In this case, the Sponsor will assess the case fully (e.g., clinically and 
immune test results) and advise whether an explant of any units is advisable. 
 Subject becomes pregnant. 
 Subjects with a new diagnosis of rheumatoid arthritis or other autoimmune-type 
disease who begins a regimen of immunosuppressive therapies.  Prior to withdrawing 
the subject, the site investigator should notify the Sponsor. 
 Implanted units appear to be damaged or malfunctioning (e.g., localized infections, 
damaged unit, lack of efficacy).  Note: In the case of a suspected malfunctioning or 
damaged unit, the Sponsor will assess the case fully and advise whether an explant of 
any units is advisable.  Explant of one VC-01-250 unit may occur in this situation 
without requiring the withdrawal of the subject from the study upon request from the 
Sponsor.      
If a subject meets any of these criteria, the VC-01-250 units and any remaining VC-01-20 and/or 
Comparator sentinel units will be explanted.  The subject will be asked to follow-up with the 
study site for three (3) years post-explant in the long-term follow-up study. 
13.6.1. 
Handling of Withdrawals 
Subjects who are withdrawn from the study will have the VC-01-250 units and VC-01-20 and/or 
Comparator sentinel units explanted.  If a subject withdraws from the trial and also withdraws 
consent for disclosure of future information in writing, no further evaluations should be 
performed, and no additional data should be collected.  The Sponsor may retain and continue to 
use any data collected before withdrawal of consent. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  It is recommended that 3 attempts by telephone and at least 3 attempts by certified letter 
should be made.  All attempts to contact the subject must be documented in the subject’s medical 
record.  Procedures will be put in place at each site to ensure that if a subject loses contact with 
the trial site, alternative measures will be utilized for the collection of information.  This may 

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include contacting family members and health care providers and, when appropriate, using 
subject location services. In any circumstance, every effort should be made to document the 
subject’s outcome, if possible, and to advise the subject to return to the clinic for explantation of 
VC-01-250 units and VC-01-20 and/or Comparator sentinel units.   
Subjects who have not withdrawn consent, but who have been discontinued from the main study 
prematurely (with products explanted) will be rolled over into a 3-year, long-term, follow-up 
trial.  Those subjects may initiate any other therapy as needed (prohibited medications will not 
apply to them). 
For safety reasons, all early termination procedures (including explantation procedure) as 
described in Visit 18/ET and Visit 19 should be performed if a subject discontinues the trial.    
13.7. 
Study Discontinuation 
Withdrawal due to AE should be distinguished from withdrawal due to insufficient response and 
recorded on the appropriate AE CRF page.  The reason for study discontinuation will be 
documented. 
When a subject withdraws due to an SAE, the SAE must be reported in accordance with the 
reporting requirements previously defined. 
When a subject withdraws from the study, the units and remaining sentinels will be explanted 
and evaluated.  The subject will be required to follow-up with the site and other health care 
professionals to ensure the appropriate insulin regimen is implemented. 
13.8. 
Future Evaluation of Explanted Units 
Evaluation of the explanted units is previously described.  However, evaluated units will not be 
discarded, and there is the possibility of other future evaluations.  
14. 
DATA HANDLING AND RECORD KEEPING 
14.1. 
Data Management Responsibilities 
As used in this protocol, the term CRF should be understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method used in this study. A 
CRF is required and should be completed for each included subject.  The completed original 
CRFs are the sole property of the Sponsor and should not be made available in any form to third 
parties, except for authorized representatives of the Sponsor or appropriate regulatory authorities, 
without written permission from the Sponsor. 
14.2. 
Data Capture Methods 
The Investigator shall capture data in the form and manner required by the Sponsor.  The 
Investigator has ultimate responsibility for the collection and reporting of all clinical and safety 
data entered on the CRFs and any other data collection forms (e.g., source documents) and 
ensuring that they are accurate, authentic, original, attributable, complete, consistent, legible, 

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timely (contemporaneous), enduring, and available when required.  The Investigator or 
appropriate site personnel must sign (electronically or hard copy) the CRF(s) to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry. 
14.3. 
Types of Data 
In most cases, the source documents (the first recording of the data) are the hospital’s or the 
physician’s subject chart, laboratory reports, etc.  The data collected on the CRFs must match the 
source data.  Source documents also include, but are not limited to, the data captured by the 
subject in the study diary such as SMBG data, insulin dose logs, PROM instruments, and 
hypoglycemia event entries.  There may be cases where the CRF, or part of the CRF, may serve 
as a source document.  In these cases, a document should be available at the Investigator’s site as 
well as at the Sponsor and clearly identify those data that will be recorded in the CRF, and for 
which the CRF will stand as the source document.   
It is expected that laboratory data (e.g., MMTT, CGM blood glucose data, ultrasound results, 
etc.), traceable to a particular subject, will be transmitted electronically to the study database in 
an ongoing manner during the study. 
14.4. 
Study Records Retention 
To enable evaluations and/or audits from regulatory authorities or the Sponsor and its designees, 
the Investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, e.g., CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (e.g., letters, e-mails, meeting minutes, telephone calls, reports).  The records 
should be retained by the Investigator according to International Conference on Harmonisation 
(ICH) local regulations, or as specified in the Clinical Study Agreement (CSA), whichever is 
longer. 
If the Investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), the Sponsor should be prospectively notified.  The 
study records must be transferred to a designee acceptable to the Sponsor, such as another 
Investigator, another institution, or to an independent third party arranged by the Sponsor.  
The Investigator must obtain the Sponsor’s written permission before disposing of any records.  
14.5. 
Protocol Deviations 
Every attempt to follow the protocol as written must be made.  However, it is expected that there 
may be deviations resulting from circumstances beyond control or unintentional oversights or 
mistakes.  These deviations from the protocol must be documented at the site, and the Sponsor 
must be notified.  Depending on the particular IRB/REB used at each site, notification of the 
IRB/REB may be warranted as well. 

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15. 
DATA PROTECTION 
The subject’s protected healthcare information shall be treated in compliance with all applicable 
laws and regulations.  When archiving or processing the protected healthcare information of the 
subjects, the Institution, Investigator, Sponsor and designees shall take all appropriate measures 
to safeguard and prevent access to these data by any unauthorized third party. 
 
 
 

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16. 
LITERATURE REFERENCES 
1. 
Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting 
plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination 
surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 
Jul 2 2011;378(9785):31-40. 
2. 
Centers for Disease Control and Prevention. National diabetes fact sheet: national 
estimates and general information on diabetes and prediabetes in the United States, 2011. 
Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and 
Prevention, 2011. 
3. 
American Diabetes Association.  Economic Costs of Diabetes in the U.S. in 2012.  
Diabetes Care, published online March 6, 2013. 
4. 
Bode BW, Schwartz S, Stubbs HA, Block JE. Glycemic characteristics in continuously 
monitored patients with type 1 and type 2 diabetes: normative values. Diabetes Care. Oct 
2005;28(10):2361-2366. 
5. 
Seaquist ER, Anderson J, Childs BC, Cryer P, Dagogo-Jack S, Fish L, Heller SR, 
Rodriguez H, Rosenzweig J, and Vigersky R. Hypoglycemia and Diabetes:  A Report of a 
Workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care,  
published online April 15, 2013. 
6. 
Sorenby AK, Wu GS, Zhu S, Wernerson AM, Sumitran-Holgersson S, Tibell AB. 
Macroencapsulation protects against sensitization after allogeneic islet transplantation in rats. 
Transplantation. Aug 15 2006;82(3):393-397. 
7. 
Lee SH, Hao E, Savinov AY, Geron I, Strongin AY, Itkin-Ansari P. Human beta-cell 
precursors mature into functional insulin-producing cells in an immunoisolation device: 
implications for diabetes cell therapies. Transplantation. Apr 15 2009;87(7):983-991. 
8. 
Bradley C, Plowright R, Stewart J, Valentine J, Witthaus E. The Diabetes Treatment 
Satisfaction Questionnaire change version (DTSQc) evaluated in insulin glargine trials shows 
greater responsiveness to improvements than the original DTSQ. Health Qual Life Outcomes. 
2007 Oct 10;5:57. 
9. 
Bradley C.  The Diabetes Treatment Satisfaction Questionnaire: DTSQ.  In Handbook of 
Psychology and Diabetes: a guide to psychological measurement in diabetes research and 
practice. Bradley C, Ed. Chur, Switzerland: Harwood Academic Publishers, 1994; 111-132. 
10. 
Bradley C, Gamsu DS. Guidelines for encouraging psychological well-being: report of a 
working group of the World Health Organisation Regional Office for Europe and International 
Diabetes Federation European Region St. Vincent Declaration Action Programme for Diabetes.  
Diabetic Medicine, 1994 Jun;11(5), 510-516. 
 
 

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17. 
SUPPLEMENTS AND APPENDICES 
 
 
 

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Table 1: 
SCHEDULE OF ASSESSMENTS [COHORT 1 T1DM; N=3 to 30 SUBJECTS] 
 
V1 a 
Screen 
V2 
Screen 
V3 
Enroll 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
or ET 
V19 
Follow
-Up 
Assessments 
Wk -4 
Wk -3 
Day 1 
Day 2 
Day 5 
Wk 2 
Wk 4 
Wk 8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
26 
Wk 39 
Wk 
52 
Wk 
65 
Wk 
78 
Wk 
91 
Wk 
104 
Wk 
105 
Visit Window 
 
 
 
+1d 
+2d 
+/-2d 
+/-3d 
+/-7d 
+/-7d 
+/-7d 
+/-7d 
+/-7d 
+/-14d 
+/-
14d 
+/-
14d 
+/-
14d 
+/-
14d 
+/-7d 
+/-3d 
ICD 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Entry Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med Hx; Prior Meds 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROM administration b 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Physical Exam c 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight/Vitals 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug screen 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology for HBsAg, HCV, 
HIV (1&2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemat/Chem 
X 
Xd 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HbA1c 
X 
 
X 
 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
FSH & UPT e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting C-peptide 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stimulated C-peptide 
X 
 
 
 
 
 
 
Xf 
Xf 
Xf 
Xf 
 
Xf 
 
 
Xf 
 
 
 
Dispense /Review CGM 
supplies and data 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense /Review Diary Data 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense/Review SMBG 
supplies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine albumin/creat  
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Fasting serum lipid panel 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 

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V1 a 
Screen 
V2 
Screen 
V3 
Enroll 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
or ET 
V19 
Follow
-Up 
Assessments 
Wk -4 
Wk -3 
Day 1 
Day 2 
Day 5 
Wk 2 
Wk 4 
Wk 8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
26 
Wk 39 
Wk 
52 
Wk 
65 
Wk 
78 
Wk 
91 
Wk 
104 
Wk 
105 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
4-hr MMTT/C-peptide & 
Glucose  
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
2-hr MMTT/C-peptide & 
Glucose  
 
 
 
 
 
 
 
Xg 
Xg 
Xg 
Xg 
 
Xg 
 
 
Xg 
 
 
 
Immune panel 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
Reserve blood samples 
 
 
X 
X (up to four additional time-points as determined by Sponsor) 
 
Photographic documentation  
(in a select group of subjects) 
 
 
X (2) 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X (2) 
X 
Implant 2 VC-01-250 units 
 
 
X (2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implant 4 to 6 Sentinels 
 
 
X (4-6) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Explant Sentinel  
 
 
 
X (up to 6 time-points; as determined by Sponsor) 
 
Explant VC-01-250 units h 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X (2) 
 
Ultrasound (safety) – unit 
evaluation and function i 
 
 
 
 
 
 
X 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
Ultrasound (pre-surgical) – 
identify unit locations i 
 
 
 
X (time-points TBD based on explant procedures) 
X 
 
Video (in a select group of 
subjects) 
 
 
X 
X (additional time-points TBD based on explant procedures) 
X 
 
AE and Con Med 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ICD for 3-year follow-up study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
a. 
Visit 1 (Week -4) screening procedures should preferably all occur on the same day with all results available prior to scheduling Visit 2 (Week -3) 
for subjects who appear to meet the eligibility criteria. There is no need to wait a full two weeks between Visit 1 and 2 if all results are available. 
Visit 4 (Day 2) has a +1 day window. Visit 5 (Day 5) has a +2 day window.  Visit 6 (Week 2) has a ±2-day window.  Visit 7 (Week 4) and Visit 19 
(Week 105) have a ±3-day window.  Visits 8, 9, 10, 11, 12, and 18 have a ±7-day window.  All remaining visits have a ±14-day window. Clinic 
visits in which the subject must arrive in a fasted state are: Visit 1 (Week -4), Visit 2 (Week -3), Visit 3 (Day 1), Visit 8 (Week 8), Visit 9 (Week 
12), Visit 10 (Week 16), Visit 11 (Week 20), Visit 12 (Week 26), Visit 13 (Week 39), Visit 14 (Week 52), Visit 16 (Week 78), Visit 18/ET (Week 
104). 

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b. The DTSQs version will be administered at Visit 2 (Week -3), Visit 3 (Day 1), Visit 12 (Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and 
Visit 18 (Week 104/ET).  DTSQc version will be administered at Visit 14 (Week 52) and Visit 18 (Week 104/ET) only. The ADDQoL will be 
administered at Visit 2 (Week -3), Visit 3 (Day 1), Visit 12 (Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and Visit 18 (Week 104/ET).  
Available electronic tablet diary data can be reviewed by the site staff as needed via a web-portal.   
c. 
It is recommended that the same qualified site personnel complete these assessments for a subject at every visit throughout the study.  Different 
types of Physical Exams will be performed throughout the study.  Complete PE: Visit 1 (Week -4), Visit 12 (Week 26), Visit 18 (Week 104); 
Abbreviated PE: Visit 3 (Day 1), Visit 7 (Week 4), Visit 9 (Week 12), Visit 14 (Week 52), visit 16 (Week 78); Targeted PE performed at visits post 
implant and post explant and may include: Visit 4 (Day 2), Visit 5 (Day 5), Visit 10 (Week 16), Visit 13 (Week 39), Visit 19 (Week 105), and 
appropriate unplanned visits. 
d. No hematology panel is evaluated at Visit 2.  Only the chemistry panel will be tested at the central laboratory. 
e. 
Only females of non-childbearing potential will be allowed enrollment. 
f. 
The stimulated C-peptide should be obtained via the simplified oral glucose challenge test only if the subject’s C-peptide levels remain 
immeasurable (<0.1 ng/mL) since implant. 
g. The 2-hour MMTT should be performed only if the subject’s stimulated C-peptide levels is measurable (>0.1 ng/mL) since implant. 
h. Explant of one VC-01-250 unit could occur prior to Visit 18 only at the discretion of the Sponsor (Section 7.8) 
Ultrasounds will be done prior to any explantation procedure to determine the location of the implanted units.  Subjects will have the ultrasound performed 
within a 3-day window to the scheduled explant of the VC-01-250 or VC-01-20 and/or Comparator sentinel units.  When appropriate, the ultrasound performed 
prior to explantation is the same one done for safety reasons to measure possible lumen expansion.

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Table 2: 
SCHEDULE OF ASSESSMENTS [COHORT 2; N=36 to 39 SUBJECTS] 
 
V1 a 
Screen 
V2 
Screen 
V3 
Enroll 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
or ET 
V19 
Follow-
Up 
Assessments 
Wk -4 
Wk -3 
Day 1 
Day 2 
Day 5 
Wk 2 
Wk 4 
Wk 8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
26 
Wk 
39 
Wk 
52 
Wk 
65 
Wk 
78 
Wk 
91 
Wk 
104 
Wk 105 
Visit Windows 
 
 
 
+1d 
+2d 
+/-2d 
+/-3d 
+/-7d 
+/-
7d 
+/-7d 
+/-7d 
+/-7d 
+/-
14d 
+/-
14d 
+/-
14d 
+/-
14d 
+/-
14d 
+/-7d 
+/-3d 
ICD 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Entry Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med Hx; Prior Meds 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROM administrationb 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Physical Exam c 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight/Vitals 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug screen 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology for HBsAg, HCV, 
HIV (1&2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemat/Chem 
X 
Xd 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HbA1c 
X 
 
X 
 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
FSH & UPT e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting C-peptide 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stimulated C-peptide 
X 
 
 
 
 
 
 
Xf 
Xf 
Xf 
Xf 
 
Xf 
 
 
Xf 
 
 
 
Dispense /Review CGM 
supplies and data 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense /Review Diary Data 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense/Review SMBG 
supplies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine albumin/creat 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Fasting serum lipid panel 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 

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01 MARCH 2016 
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V1 a 
Screen 
V2 
Screen 
V3 
Enroll 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
or ET 
V19 
Follow-
Up 
Assessments 
Wk -4 
Wk -3 
Day 1 
Day 2 
Day 5 
Wk 2 
Wk 4 
Wk 8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
26 
Wk 
39 
Wk 
52 
Wk 
65 
Wk 
78 
Wk 
91 
Wk 
104 
Wk 105 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
4-hr MMTT/C-peptide & 
Glucose  
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
2-hr MMTT/C-peptide & 
Glucose  
 
 
 
 
 
 
 
Xg 
Xg 
Xg 
Xg 
 
Xg 
 
 
Xg 
 
 
 
Immune panel 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
Reserve blood samples 
 
 
X 
X (up to four additional time-points as determined by Sponsor) 
 
Photographic documentation 
(in a select group of subjects) 
 
 
X (2) 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X (2) 
X 
Implant VC-01-250 units 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implant VC-01-20 sentinels 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Explant VC-01-20 sentinel h 
 
 
 
X (time-points as determined by Sponsor) 
 
Explant VC-01-250 units i 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Ultrasound (safety) – unit 
evaluation and function j 
 
 
 
 
 
 
X 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
Ultrasound (pre-surgical) – 
identify unit locations j 
 
 
 
X (time-points TBD based on explant procedures) 
X 
 
Video (in a select group of 
subjects) 
 
 
X 
X (additional time-points TBD based on explant procedures) 
X 
 
AE and Con Med 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ICD for 3-year follow-up study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
a. 
Visit 1 (Week -4) screening procedures should preferably all occur on the same day with all results available prior to scheduling Visit 2 (Week -3) 
for subjects who appear to meet the eligibility criteria. There is no need to wait a full two weeks between Visit 1 and 2 if all results are available. 
Visit 4 (Day 2) has a +1 day window. Visit 5 (Day 5) has a +2 day window.  Visit 6 (Week 2) has a ±2-day window.  Visit 7 (Week 4) and Visit 19 
(Week 105) have a ±3-day window.  Visits 8, 9, 10, 11, 12 and 18 have a ±7-day window.  All remaining visits have a ±14-day window.  Clinic 
visits in which the subject must arrive in a fasted state are: Visit 1 (Week -4), Visit 2 (Week -3), Visit 3 (Day 1), Visit 8 (Week 8), Visit 9 (Week 
12), Visit 10 (Week 16), Visit 11 (Week 20), Visit 12 (Week 26), Visit 13 (Week 39), Visit 14 (Week 52), Visit 16 (Week 78), Visit 18/ET (Week 
104). 

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b. The DTSQs version will be administered at Visit 2 (Week -3), Visit 3 (Day 1), Visit 12 (Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and 
Visit 18 (Week 104/ET).  DTSQc version will be administered at Visit 14 (Week 52) and Visit 18 (Week 104/ET) only. The ADDQoL will be 
administered at Visit 2 (Week -3), Visit 3 (Day 1), Visit 12 (Week 26), Visit 14 (Week 52), Visit 16 (Week 78), and Visit 18 (Week 104/ET).  
Available electronic tablet diary data can be reviewed by the site staff as needed via a web-portal.   
c. 
It is recommended that the same qualified site personnel complete these assessments for a subject at every visit throughout the study. Different 
types of Physical Exams will be performed throughout the study.  Complete PE: Visit 1 (Week -4), Visit 12 (Week 26), Visit 18 (Week 104); 
Abbreviated PE: Visit 3 (Day 1), Visit 7 (Week 4), Visit 9 (Week 12), Visit 14 (Week 52), visit 16 (Week 78); Targeted PE performed at visits post 
implant and post explant and may include: Visit 4 (Day 2), Visit 5 (Day 5), Visit 10 (Week 16), Visit 13 (Week 39), Visit 19 (Week 105), and 
appropriate unplanned visits 
d. No hematology panel is evaluated at Visit 2.  Only the chemistry panel will be tested at the central laboratory. 
e. 
Only females of non-childbearing potential will be allowed enrollment. 
f. 
The stimulated C-peptide should be obtained via the simplified oral glucose challenge test only if the subject’s C-peptide levels remain 
immeasurable (<0.1 ng/mL) since implant. 
g. The 2-hour MMTT should be performed only if the subject’s stimulated C-peptide levels is measurable (>0.1 ng/mL) since implant. 
h. As described in the protocol, up to three (3) VC-01-20 sentinel units are implanted in Cohort 2.  The VC-01-20 sentinel units will be explanted at 
various time-points determined by the Sponsor. 
i. 
Explant of one VC-01-250 unit could occur prior to Visit 18 at the discretion of the Sponsor (Section 7.8) 
j. 
Ultrasounds will be done prior to any explantation procedure to determine the location of the implanted units.  Subjects will have the ultrasound 
performed within a 3-day window to the scheduled explant of either the VC-01-250 or VC-01-20 units.  When appropriate, the ultrasound 
performed prior to explantation is the same one done for safety reasons to measure possible lumen expansion. 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol #VC01-101 
 
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Table 3: 
SCHEDULE OF ASSESSMENTS [COHORT 1 T2DM; N = Up to 5 SUBJECTS] 
 
V1 a 
Screen 
V2 
Screen 
V3 
Enroll 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
or ET 
V13 
Follow
-Up 
Assessments 
Wk -4 
Wk -3 
Day 1 
Day 2 
Day 5 
Wk 2 
Wk 4 
Wk 8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
26 
Wk 27 
Visit Window 
 
 
 
+1d 
+2d 
+/-2d 
+/-3d 
+/-7d 
+/-7d 
+/-7d 
+/-7d 
+/-7d 
+/-3d 
ICD 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Entry Criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Med Hx; Prior Meds 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam b 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Weight/Vitals 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug screen 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Serology for HBsAg, HCV, 
HIV (1&2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hemat/Chem 
X 
Xc 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
HbA1c 
X 
 
X 
 
 
 
 
 
X 
 
 
X 
 
FSH & UPT d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting C-peptide 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Stimulated C-peptide 
X 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
Dispense SMBG supplies 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urine albumin/creat  
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
Fasting serum lipid panel 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Immune panel 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
Reserve Blood Samples 
 
 
X 
X (up to four additional time-points as determined by Sponsor) 
 
Photographic documentation  
(in a select group of subjects) 
 
 
X (2) 
X 
X 
X 
 
 
 
 
 
X (2) 
X 
Implant 2 VC-01-250 units 
 
 
X (2) 
 
 
 
 
 
 
 
 
 
 
Implant 4 to 6 Sentinels 
 
 
X (4-6) 
 
 
 
 
 
 
 
 
 
 
Explant Sentinel 
 
 
 
X (time-points as determined by Sponsor) 
 
Explant VC-01-250 units e 
 
 
 
 
 
 
 
 
 
 
 
X (2)e 
 
Ultrasound (safety) – unit 
evaluation and function f 
 
 
 
 
 
 
X 
X 
X 
 
X 
X 
 
Ultrasound (pre-surgical) – 
identify unit locations f 
 
 
 
X (time-points TBD based on explant procedures) 
X 
 
Video (in a select group of 
subjects) 
 
 
X 
X (additional time-points TBD based on explant 
procedures) 
X 
 
AE and Con Med 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ICD for 3-year follow-up study 
 
 
 
 
 
 
 
 
 
 
 
X 
 

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a. 
Visit 1 (Week -4) screening procedures should preferably all occur on the same day with all results 
available prior to scheduling Visit 2 (Week -3) for subjects who appear to meet the eligibility criteria. 
There is no need to wait a full two weeks between Visit 1 and 2 if all results are available. Visit 4 (Day 
2) has a +1 day window. Visit 5 (Day 5) has a +2 day window.  Visit 6 (Week 2) has a ±2-day window.  
Visit 7 (Week 4) has a ±3-day window.  Visits 8, 9, 10, 11, and 12 have a ±7-day window.  Clinic 
visits in which the subject must arrive in a fasted state are: Visit 1 (Week -4), Visit 2 (Week -3), Visit 3 
(Day 1), Visit 8 (Week 8), Visit 9 (Week 12), Visit 10 (Week 16), Visit 11 (Week 20), and Visit 12/ET 
(Week 26). 
b. It is recommended that the same qualified site personnel complete these assessments for a subject at 
every visit throughout the study.  Different types of Physical Exams will be performed throughout the 
study.  Complete PE: Visit 1 (Week -4), Visit 12 (Week 26); Abbreviated PE: Visit 3 (Day 1), Visit 7 
(Week 4), Visit 9 (Week 12); Targeted PE performed at visits post implant and post explant and may 
include: Visit 4 (Day 2), Visit 5 (Day 5), Visit 10 (Week 16) and appropriate unplanned visits. 
c. 
No hematology panel is evaluated at Visit 2.  Only the chemistry panel will be tested at the central 
laboratory. 
d. Only females of non-childbearing potential will be allowed enrollment. 
e. 
Explant of a VC-01-250 unit could occur prior to Visit 12 
f. 
Ultrasounds will be done prior to any explantation procedure to determine the location of the 
implanted units.  Subjects will have the ultrasound performed within a 3-day window to the scheduled 
explant of the VC-01-250 or VC-01-20 and/or Comparator sentinel units.  When appropriate, the 
ultrasound performed prior to explantation is the same one done for safety reasons to measure possible 
lumen expansion. 

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APPENDIX A. DIABETES TREATMENT SATISFACTION 
QUESTIONNAIRE (STATUS) – DTSQS 
The following questions are concerned with the treatment for your diabetes (including insulin, 
tablets and/or diet) and your experience over the past few weeks.  Please answer each question by 
circling a number on each of the scales. 
1. 
How satisfied are you with your current treatment? 
 
very satisfied 
 
6 
5 
4 
3 
2 
1 
0 
 
very dissatisfied 
 
 
2. 
How often have you felt that your blood sugars have been unacceptably high recently? 
 
most of the time 
 
6 
5 
4 
3 
2 
1 
0 
 
none of the time 
 
 
3. 
How often have you felt that your blood sugars have been unacceptably low recently? 
 
most of the time 
 
6 
5 
4 
3 
2 
1 
0 
 
none of the time 
 
 
4. 
How convenient have you been finding your treatment to be recently? 
 
very convenient 
 
6 
5 
4 
3 
2 
1 
0 
 
very inconvenient 
 
 
5. 
How flexible have you been finding your treatment to be recently? 
 
very flexible 
 
6 
5 
4 
3 
2 
1 
0 
 
very inflexible 
 
 
6. 
How satisfied are you with your understanding of your diabetes? 
 
very satisfied 
 
6 
5 
4 
3 
2 
1 
0 
 
very dissatisfied 
 
 
7. 
Would you recommend this form of treatment to someone else with your kind of diabetes? 
 
Yes, I would definitely 
recommend the 
treatment 
 
6 
5 
4 
3 
2 
1 
0 
 
No, I would 
definitely not 
recommend the 
treatment 
 
 
8. 
How satisfied would you be to continue with your present form of treatment? 
 
very satisfied 
 
6 
5 
4 
3 
2 
1 
0 
 
very dissatisfied 
Please make sure that you have circled one number on each of the scales. 

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APPENDIX B. DIABETES TREATMENT SATISFACTION 
QUESTIONNAIRE (CHANGE) – DTSQC 
For the past 12 months you have been taking part in a diabetes treatment study.  At the start of the study 
you may have had a change of treatment.  Today we would like to know how your experience of your 
current treatment (including medication and diet) has changed from your experience of treatment before 
the study began.  Please answer each question by circling a number on each of the scales to indicate the 
extent to which you have experienced changes.  If you have experienced no change, please circle ‘0’. 
1. 
How satisfied are you with your current treatment? 
 
much more 
satisfied now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less 
satisfied now 
 
2. 
How often have you felt that your blood sugars have been unacceptably high recently? 
 
much more of 
the time now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less of 
the time now 
 
3. 
How often have you felt that your blood sugars have been unacceptably low recently? 
 
much more of 
the time now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less of 
the time now 
 
4. 
How convenient have you been finding your treatment to be recently? 
 
much more 
convenient now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less 
convenient now 
 
5. 
How flexible have you been finding your treatment to be recently? 
 
much more 
flexible now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less 
flexible now 
 
6. 
How satisfied are you with your understanding of your diabetes? 
 
much more 
satisfied now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less 
satisfied now 
 
7. 
How likely would you be to recommend your present treatment to someone else with your kind of 
diabetes? 
 
much more likely to 
recommend the 
treatment now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less likely 
to recommend the 
treatment now 
 
8. 
How satisfied would you be to continue with your present form of treatment? 
 
much more 
satisfied now 
3 
2 
1 
0 
-1 
-2 
-3 
 
much less 
satisfied now 
 
 
Please make sure that you have circled one number on each of the scales. 

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APPENDIX C. AUDIT OF DIABETES DEPENDENT QUALITY OF LIFE 
(ADDQOL) 
This questionnaire asks about your quality of life – in other words how good or bad you feel your 
life is. 
Please put an “X” in the box that best indicates your response for each item.  
What we want to know is how you feel about your life now. 
 
I) In general, my present quality of life is: 
 
 
 
 
 
 
 
 
 
excellent 
very good 
good 
neither 
good nor 
bad 
bad 
very bad 
extremely 
bad 
Now we would like to know how your quality of life is affected by your diabetes, its management 
and any complications you may have. 
 
II) If I did not have diabetes, my quality of life would be: 
 
 
 
 
 
 
 
very much better 
much      better 
a little      better 
the same 
Worse 
 
Please respond to the more specific items on the pages that follow.  For each aspect of life described, 
you will find two parts: 
 
For Part (a): 
put an “X” in one box to show how diabetes affects this aspect of your life; 
For Part (b): 
put an “X” in one box to show how important this aspect of your life is to your quality of life. 
 
1 
(a) If I did not have diabetes, I would enjoy my leisure activities:  
 
 
 
 
 
 
 
very much more 
much more 
a little more 
the same 
less 
 
(b) My leisure activities are:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 

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2 
Are you currently working, looking for work or would like to work?  
 
Yes  If yes, complete (a) and (b). 
 
No  If no, go straight to Question 3. 
 
(a) If I did not have diabetes, my work life would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) For me, having a work life is: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
3 
(a) If I did not have diabetes, local or long distance travel would be: 
 
 
 
 
 
 
 
very much easier  
much easier 
a little easier 
the same 
more difficult 
 
(b) For me, local or long distance travel are: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
4 
Do you ever go on vacation or want to go on vacation?  
 
Yes  If yes, complete (a) and (b). 
 
No  If no, go straight to Question 5. 
 
(a) If I did not have diabetes, my vacations would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) For me, vacations are: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
5 
(a) If I did not have diabetes, physically I could do:  
 
 
 
 
 
 
 
very much more 
much more 
a little more 
the same 
less 
 
(b) For me, how much I can do physically is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 

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6 
Do you have any family/relatives? 
 
Yes  If yes, complete (a) and (b). 
 
No  If no, go straight to Question 7. 
 
(a) If I did not have diabetes, my family life would be 
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My family life is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
7 
(a) If I did not have diabetes, my friendships and social life would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My friendships and social life are:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
8 
Do you have or would you like to have a close personal relationship (e.g. husband / wife, partner)? 
 
Yes  If yes, complete (a) and (b). 
 
No  If no, go straight to Question 9. 
 
(a) If I did not have diabetes, my closest personal relationship would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) For me, having a close personal relationship is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
 
9 
Do you have or would you like to have a sex life? 
 
Yes  If yes, complete (a) and (b). 

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No  If no, go straight to Question 10. 
 
(a) If I did not have diabetes, my sex life would be: 
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) For me, having a sex life is: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
10 (a) If I did not have diabetes, my physical appearance would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My physical appearance is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
11 (a) If I did not have diabetes, my self-confidence would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My self-confidence is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
12 (a) If I did not have diabetes, my motivation would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My motivation is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
13 (a) If I did not have diabetes, the way people in general react to me would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) The way people in general react to me is:  

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 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
14 (a) If I did not have diabetes, my feelings about the future (e.g. worries, hopes) would be: 
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My feelings about the future are:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
15 (a) If I did not have diabetes, my financial situation would be:  
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My financial situation is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
 
16 (a) If I did not have diabetes, my living situation and conditions would be: 
 
 
 
 
 
 
 
very much better 
much better 
a little better 
the same 
worse 
 
(b) My living situation and conditions are: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
17 (a) If I did not have diabetes, I would have to depend on others when I do not want to:  
 
 
 
 
 
 
 
very much less 
much less 
a little less 
the same 
more 
 
(b) For me, not having to depend on others is:  
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 

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18 (a) If I did not have diabetes, my freedom to eat as I want would be: 
 
 
 
 
 
 
 
very much greater 
much greater 
a little greater 
the same 
less 
 
(b) My freedom to eat as I want is: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
 
19 (a) If I did not have diabetes, my freedom to drink as I want (e.g. fruit juice, alcohol, sweetened hot and cold 
drinks) would be: 
 
 
 
 
 
 
 
very much greater 
much greater 
a little greater 
the same 
less 
 
(b) My freedom to drink as I want is: 
 
 
 
 
 
 
very important 
important 
somewhat important 
not at all important 
 
Are there any other ways in which diabetes, its management and any complications affect your 
quality of life?  If so, please write what they are below. 
 
 
 
Thank you for completing this questionnaire.