A Phase 2, Randomized, Double Blind, Placebo Controlled, Dose Range Finding Study to Access the Efficacy and Safety of Intramuscular Injection of Human Placenta- Derived Cells (PDA-002) in Subjects With Diabetic Peripheral Neuropathy.
Phase: PHASE2
Conditions: Diabetic Nephropathies, Peripheral Nervous System Diseases
Sponsor: Celularity Incorporated

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TITLE PAGE 
A PHASE 2, RANDOMIZED, DOUBLE BLIND, 
PLACEBO CONTROLLED, DOSE RANGE FINDING 
STUDY TO ASSESS THE EFFICACY AND SAFETY OF 
INTRAMUSCULAR INJECTION OF HUMAN 
PLACENTA-DERIVED CELLS (PDA-002) IN SUBJECTS 
WITH DIABETIC PERIPHERAL NEUROPATHY 
 
INVESTIGATIONAL PRODUCT: 
 
PDA-002 
PROTOCOL NUMBER: 
 
CCT-PDA-002-DPN-001 
DATE FINAL: 
 
8 June 2015  
AMENDMENT: No. 1: 
 
02 September 2015 
EudraCT NUMBER: 
 
Not Applicable 
IND NUMBER: 
 
016564 
SPONSOR NAME / ADDRESS: 
 
 
 
Celgene Corporation 
86 Morris Avenue 
Summit, NJ 07901 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 

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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION  
Name: 
Denesh K. Chitkara, MD 
Title: 
Senior Director, Clinical and Medical Affairs 
Address: 
7 Powderhorn Drive 
 
Warren, NJ 07059 
Phone: 
+1 (732) 564-5751 (Office) 
 
+1 (919) 259-6883 (Cell) 
E-mail: 
dchitkara@celgene.com 
Name: 
Denesh K. Chitkara, MD 
 
Note: The back-up 24 hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls  
Back-up 24 Hour Global Emergency Contact Call Center: +1-877-501-7738 
 

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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
 
Signature of Celgene Therapeutic Area Head 
 
 
Printed Name of Celgene Therapeutic Area Head and Title 
 
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.   
 
 
 
 

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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
 
Signature of Site Principal Investigator 
 
dd mmm yyyy 
 
 
Printed Name of Site Principal Investigator 
Institution Name:_______________________________________ 
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, International Conference on 
Harmonisation (ICH) Good Clinical Practices Guidelines, and local regulations 
governing the conduct of clinical studies. 
 

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PROTOCOL SUMMARY 
Study Title 
A Phase 2, Randomized, Double-Blind, Placebo Controlled, Dose Range Finding Study to 
Assess the Efficacy and Safety of Intramuscular Injection of Human Placenta-Derived Cells 
(PDA-002) in Subjects With Diabetic Peripheral Neuropathy 
Indication 
This study will investigate the efficacy and safety of intramuscular (IM) injections of PDA-002 
in subjects who have diabetic peripheral neuropathy (DPN) as a co-morbidity of Type 2 diabetes. 
Objectives 
The primary objective of the study is to assess the efficacy of PDA-002 versus placebo in 
subjects with DPN, based on the change from baseline in epidermal nerve histology at 6 months. 
The secondary objective of the study is to assess the safety and tolerability of IM administration 
of 2 different doses of PDA-002 or placebo in subjects with DPN. 
The key exploratory objectives of the study are to assess potential treatment effects of IM 
administration of PDA-002 in subjects with DPN as measured by changes from baseline in: 
 Epidermal nerve histology at 3 months 
 Lower limb microvascular oxygenation  
 Vascular reactivity  
 DPN signs and symptoms 
 Motor and sensory nerve conduction and autonomic function 
 Health-related quality of life 
 Vascular and immune, biomarkers, and laboratory parameters 
 Assessment of the systemic versus local efficacy of PDA-002 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, dose range finding study in 
subjects with DPN.  The study will enroll approximately 24 subjects. Subjects will be 
randomized to receive one of 3 treatments:  PDA-002 (3 x 106 cells), PDA-002 (30 x 106 cells), 
or placebo (vehicle control) in a 1:1:1 randomization approach.  Investigational product (IP) or 
placebo will be administered monthly (3 administrations total; Study Days 1, 29, and 57).  
Subjects will be evaluated for efficacy and safety for approximately one year from the day of the 
last IP administration. 
Study Population 
The study population includes subjects with Diabetic Peripheral Neuropathy due to Type 2 
diabetes mellitus (DM) as defined by the ADA or WHO criteria (Appendix A). 

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Length of Study 
Subjects are expected to participate in the study from screening (Day 28) to 1 year after the -last 
IP injection.   
Subjects will undergo a Screening Period of up to 28 days. During the Screening Period 
eligibility will be confirmed and baseline assessments will be performed. Subjects will then enter 
a 6 month Treatment Period consisting of 8 study visits.  During the Treatment Period, IP will be 
administered on Study Days 1, 29, and 57, and efficacy and safety evaluations will be performed 
as outlined in the Table of Events (Table 1).  Subjects will then enter a Follow-up Period.  The 
Follow up Period will consist of bi-monthly study visits to continue to assess safety and longer-
term efficacy. 
End of Trial 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date. 
Study Treatments 
Subjects will be randomized 1:1:1 to receive one of the following dose levels of IP: 
 PDA-002 Dose Level 1:  3 x 106 PDA-002 cells administered IM on Study Days 1, 
29, and 57.*  
 PDA-002 Dose Level 2:  30 x 106 PDA-002 cells administered IM on Study Days 1, 
29, and 57.* 
 Placebo (vehicle control) subjects will receive placebo (vehicle control) administered 
in the same manner and at the same time points as the PDA-002 dosing groups. 
*Subjects will be dosed in the same leg.  The leg of injection will be the leg with the 
lowest combined qualifying NTSS-6 and UENS and NIS-LL score.  In the case of a 
subject with an equal score for both legs, the choice of the leg to inject is at the 
discretion of the investigator.  
PDA-002 and placebo (vehicle control) units will be shipped to the study sites as cryopreserved 
units and will be thawed and filled into syringes prior to IM injection. 
Overview of Key Efficacy Assessments 
The following efficacy assessments will be performed as outlined in the Table of Events 
(Table 1). 
The primary efficacy assessment is the evaluation of change from baseline in Epidermal Nerve 
Fiber Density (ENFD) at 6 months. 
Efficacy will also be assessed in an exploratory manner by evaluating changes from baseline in 
the following: 
 ENFD at 3 months 
 Microvascular oxygenation of the lower limbs by Hyperspectral Imaging (HSI) 

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 Vascular reactivity by Laser Doppler Iontophoresis and Nerve Axon Reflex 
measurements.  
 The 6-item Neuropathy Total Symptom Score (NTSS-6) assessment 
 The Neurological Impairment Score of the Lower Limb (NIS-LL) 
 The Utah Early Neuropathy Scale (UENS) 
Additional efficacy signals indicating changes in motor and sensory nerve conduction and 
autonomic function as evaluated by: 
 Nerve conduction studies  
 Quantitative Sudomotor Axon Reflex Testing (QSART).  QSART is a measurement 
of autonomic involvement by evaluating postganglionic sudomotor function deficits 
in the foot, distal leg, and distal thigh. 
Changes in health-related quality of life (QOL) will be assessed by the Norfolk QOL-DN.  
Various experimental biomarker analyses will be performed to assess changes in the vascular 
and immune profile.  Samples for biomarker analyses will include blood and epidermal tissue. In 
addition, an assessment of the systemic vs. local efficacy of PDA-002 will be evaluated.   
Overview of Safety Assessments 
Safety and tolerability will be assessed by the type, frequency, and severity of adverse events 
(AEs). As such, the following safety assessments will be performed as outlined in the Table of 
Events (Table 1). 
 Assessment of adverse events and serious adverse events (SAEs) 
 Physical examinations including complete neurological examinations and vital signs 
 Clinical laboratory tests including chemistry, hematology, urinalysis, evaluation; 
urine pregnancy testing if applicable 
 Twelve-lead electrocardiogram (ECGs) 
 Retinal assessments  
 Concomitant medications and procedures 
 Immunological assessments  
 Anti-human leukocyte antigen (HLA) antibodies 
Sample Size and Power Considerations 
The sample size of 24 subjects total, 8 per treatment arm, was selected in order to provide 
preliminary efficacy and safety information in a randomized, double-blind fashion.  The study is 
designed to provide an estimation of the treatment effect of active therapy and placebo to plan a 
sample size for the next study. 
Based upon a previous study (Jacobs, 2011), the mean ENFD was 1.56 fibers/mm at baseline and 
3.07 fibers/mm after 6 months of treatment with a standard deviation of 1.5 fibers/mm for the 
mean increase. Assuming the same treatment effect is observed from baseline, the sample size of 

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16 subjects actively on therapy resulting from combining the 2 active arms has a 96% power to 
detect a similar mean change at 6 months from baseline, with a two-sided test and a Type I error 
rate set at 0.05. Assuming the subjects treated with placebo would not have a change from 
baseline, the study has 60% power to detect similar differences between placebo and active 
therapy with PDA-002, with a two-sided test and a Type I error rate set at 0.05. 
Efficacy and Safety Analyses 
The planned efficacy and safety analyses will be fully described in a comprehensive SAP.  
The efficacy analyses will also include a descriptive assessment of the exploratory objective to 
evaluate whether the treatment effect of PDA-002 is systemic or local.  This will be done by 
taking into account the intersubject variability between measurements taken from the left and the 
right leg. 

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
PROTOCOL SUMMARY ...............................................................................................................5 
1. 
INTRODUCTION ......................................................................................................15 
2. 
STUDY OBJECTIVES ..............................................................................................18 
2.1. 
Primary Objective .......................................................................................................18 
2.2. 
Secondary Objective ...................................................................................................18 
2.3. 
Exploratory Objectives ...............................................................................................18 
3. 
STUDY ENDPOINTS ................................................................................................19 
3.1. 
Primary Endpoint ........................................................................................................19 
3.2. 
Secondary Endpoint ....................................................................................................19 
3.3. 
Exploratory Endpoints ................................................................................................19 
4. 
OVERALL STUDY DESIGN ....................................................................................20 
4.1. 
Study Design ...............................................................................................................20 
4.2. 
Study Design Rationale ..............................................................................................20 
4.3. 
Study Duration ............................................................................................................22 
4.4. 
End of Trial .................................................................................................................22 
5. 
TABLE OF EVENTS .................................................................................................23 
6. 
PROCEDURES ..........................................................................................................26 
6.1. 
Study Entry/Screening Period (Visit 1) ......................................................................26 
6.2. 
Treatment Period (Visit 2 through Visit 9) .................................................................30 
6.3. 
Follow-Up Period .......................................................................................................30 
6.4. 
Efficacy Procedures ....................................................................................................30 
6.5. 
Safety ..........................................................................................................................32 
6.5.1. 
External Data Monitoring Committee ........................................................................33 
7. 
STUDY POPULATION .............................................................................................34 
7.1. 
Number of Subjects and Sites .....................................................................................34 
7.2. 
Inclusion Criteria ........................................................................................................34 
7.3. 
Exclusion Criteria .......................................................................................................34 
8. 
DESCRIPTION OF STUDY TREATMENTS ..........................................................37 
8.1. 
Description of Investigational Product .......................................................................37 
8.2. 
Treatment Administration and Schedule ....................................................................37 

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8.2.1. 
Discontinuation ...........................................................................................................38 
8.2.2. 
Overdose .....................................................................................................................38 
8.3. 
Method of Treatment Assignment ..............................................................................39 
8.4. 
Packaging and Labeling ..............................................................................................39 
8.5. 
Investigational Product Accountability and Disposal .................................................39 
8.6. 
Investigational Product Compliance ...........................................................................40 
8.7. 
Blinding ......................................................................................................................41 
9. 
CONCOMITANT MEDICATIONS AND PROCEDURES ......................................42 
9.1. 
Permitted Concomitant Medications and Procedures .................................................42 
9.2. 
Prohibited Concomitant Medications and Procedures ................................................42 
9.3. 
Required Concomitant Medications and Procedures ..................................................42 
10. 
STATISTICAL ANALYSES .....................................................................................43 
10.1. 
Overview .....................................................................................................................43 
10.2. 
Study Population Definitions ......................................................................................43 
10.3. 
Sample Size and Power Considerations .....................................................................43 
10.4. 
Background and Demographic Characteristics ..........................................................44 
10.5. 
Subject Disposition .....................................................................................................44 
10.6. 
Efficacy Analysis ........................................................................................................44 
10.7. 
Safety Analysis ...........................................................................................................44 
10.8. 
Interim Analysis ..........................................................................................................45 
11. 
ADVERSE EVENTS ..................................................................................................46 
11.1. 
Monitoring, Recording and Reporting of Adverse Events .........................................46 
11.2. 
Evaluation of Adverse Events ....................................................................................46 
11.2.1. 
Seriousness .................................................................................................................47 
11.2.2. 
Severity / Intensity ......................................................................................................48 
11.2.3. 
Causality .....................................................................................................................48 
11.2.4. 
Duration ......................................................................................................................49 
11.2.5. 
Action Taken ..............................................................................................................49 
11.2.6. 
Outcome ......................................................................................................................49 
11.3. 
Abnormal Laboratory Values .....................................................................................49 
11.4. 
Pregnancy ...................................................................................................................49 
11.4.1. 
Females of Childbearing Potential ..............................................................................50 
11.4.2. 
Male Subjects ..............................................................................................................50 

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11.5. 
Reporting of Serious Adverse Events .........................................................................50 
11.5.1. 
Safety Queries .............................................................................................................51 
11.6. 
Expedited Reporting of Adverse Events .....................................................................51 
12. 
DISCONTINUATIONS .............................................................................................52 
12.1. 
Treatment Discontinuation .........................................................................................52 
12.1.1. 
Events Leading to Suspension of Enrollment Pending DMC Evaluation ..................52 
12.1.2. 
Mandatory Treatment Discontinuations .....................................................................52 
12.1.3. 
Additional Treatment Discontinuations ......................................................................52 
12.2. 
Study Discontinuation ................................................................................................53 
13. 
EMERGENCY PROCEDURES ................................................................................54 
13.1. 
Emergency Contact .....................................................................................................54 
13.2. 
Emergency Identification of Investigational Products ...............................................54 
14. 
REGULATORY CONSIDERATIONS ......................................................................55 
14.1. 
Good Clinical Practice ................................................................................................55 
14.2. 
Investigator Responsibilities .......................................................................................55 
14.3. 
Subject Information and Informed Consent ...............................................................56 
14.4. 
Confidentiality ............................................................................................................56 
14.5. 
Protocol Amendments ................................................................................................56 
14.6. 
Institutional Review Board/Independent Ethics Committee Review and 
Approval .....................................................................................................................56 
14.7. 
Ongoing Information for Institutional Review Board / Ethics Committee ................57 
14.8. 
Termination of the Study ............................................................................................57 
15. 
DATA HANDLING AND RECORDKEEPING .......................................................59 
15.1. 
Data/Documents .........................................................................................................59 
15.2. 
Data Management .......................................................................................................59 
15.3. 
Record Retention ........................................................................................................59 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................61 
16.1. 
Study Monitoring and Source Data Verification ........................................................61 
16.2. 
Audits and Inspections ................................................................................................61 
17. 
PUBLICATIONS .......................................................................................................62 
18. 
REFERENCES ...........................................................................................................63 
19. 
APPENDICES ............................................................................................................64 

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Appendix A:  American Diabetes Association (ADA) and World Health Organization 
(WHO) Diabetes Mellitus Type 2 Definition .............................................................64 
Appendix B:  International Clinical Diabetic Retinopathy Disease Severity Scale .....................66 
Appendix C:  New York Heart Association (NYHA) Classification ...........................................67 
Appendix D:  Canadian Cardiovascular Society Angina Grading Scale .....................................68 
Appendix E:  Thawing Protocol ...................................................................................................69 
 

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LIST OF TABLES 
Table 1: 
Table of Events ...........................................................................................................23 
 

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LIST OF FIGURES 
Figure 1: 
Overall Study Design ..................................................................................................22 
 
 

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1. 
INTRODUCTION  
Diabetes mellitus (DM) is a disease in which hyperglycemia damages the nerves, kidneys, eyes, 
and blood vessels over time. The estimated incidence of diabetes in the United States (US) 
exceeds 1.9 million new cases annually, with an overall prevalence of over 25 million people or 
8.3% of the US population (Centers for Disease Control and Prevention, 2011).  Type 2 DM 
(adult onset or non-insulin dependent diabetes) is by far the most common form, occurring in 
about 95% of subjects diagnosed with diabetes. Diabetic polyneuropathy (DPN) is the most 
common complication of DM.  It develops on a background of long standing, chronic 
hyperglycemia, associated metabolic derangements, and cardiovascular risk factors. 
Although the underlying mechanisms of DPN remain unclear, central features in the 
development and progression of DPN are neural cell degeneration and decreased nerve blood 
flow, and are usually associated with both axonal degeneration and demyelination.  This results 
in spontaneous pain (burning pain, electrical or stabbing sensations, deep aching pain, etc.), 
hyperalgesia, and diminished sensation which is typically worse at night.  
Therapies for the treatment of DPN are currently limited to pain relief (tricyclic antidepressants, 
serotonin norepinephrine reuptake inhibitors, anticonvulsants, opioids, and non-prescription 
analgesics).  There are currently no treatments approved to treat the underlying disease.  
Human placenta-derived cells (PDA-002) are characterized as a cellular immune modulating 
agent that has the potential to induce angiogenesis. PDA-002 is a mesenchymal-like cell 
population derived from normal, full-term human placental tissue.  PDA-002 is culture-expanded 
as a plastic-adherent, undifferentiated in vitro cell population that expresses the nominal 
phenotype CD34-, CD10+, CD105+ and CD200+.  PDA-002 cells constitutively express 
moderate levels of human leukocyte antigen (HLA) Class I and undetectable levels of HLA 
Class II, and they do not express the co-stimulatory molecules CD80 and CD86.  PDA-002 is 
genetically stable, displaying a normal diploid chromosome count, normal karyotype, and 
exhibits normal senescence after prolonged in vitro culture. 
Similar to mesenchymal stromal cells (MSCs) (Aggarwal, 2005; Nauta, 2007) in vitro studies 
have shown that PDA-002 is capable of immunomodulation. PDA-002 suppresses T-cell 
proliferation and modulates other cell types involved in immune and inflammatory responses 
such as T-cell subsets, macrophages and dendritic cells. 
In vivo biodistribution and safety studies using mouse models have demonstrated that PDA-002 
cells do not proliferate in any tissues and are not associated with any observed toxicity or tumor 
formation. In a biodistribution study, PDA-002 cells were not detectable at Day 8 in the injected 
muscle by bioluminescence imaging. The cells did not distribute to other organs, including the 
lungs. The cells were only detected at the site of injection and in the draining lymph nodes. 
The potential beneficial effects of PDA-002 on cellular components of the neurovascular system 
were tested using a variety of in vitro and in vivo experimental systems.  The capacity of 
PDA-002 to elaborate angiogenic factors, induce endothelial cell survival/proliferation, induce 
endothelial cell migration, and induce endothelial cell tube formation was assessed. 

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In rat and mouse models of peripheral neuritis, placental-derived cells have demonstrated dose 
dependent analgesic effects including pain reduction, suppressed immune cell infiltration, and 
reduced mechanical sensitivity. The analgesic effects were equivalent to high dose gabapentin. 
Additionally, treatment with PDA-002 in mouse hind limb ischemia models demonstrated 
improvement in blood flow and induced the formation of new collateral blood vessels suggesting 
angiogenic activity. The effects were comparable to VEGF controls. Please refer to the 
Investigator’s Brochure for details of these studies.  
PDA-002 is currently being investigated in 3 independent human studies in subjects with 
complications of DM.  The initial (ongoing) phase 1 open-label, dose escalation study (CCT-
PDA-002-DFU-001) is being conducted in 15 subjects with peripheral arterial disease (PAD) 
with diabetic foot ulceration (DFU) who were refractory to conventional therapy.  In this study, 
intramuscular (IM) injection of either 3 x 106, 10 x 106, 30 x 106, or 100 x 106 PDA-002 cells per 
treatment on Study Day 1 and Study Day 9 in the affected lower limb was being investigated.  
Though designed as a safety study, results have demonstrated efficacy in the healing or closure 
of the index ulcer within 3 months following the initial dose of PDA-002 in 15 subjects to date. 
Five subjects had complete healing, and 2 subjects had approximately 50% healing of their index 
ulcer within 3 months.  There was a trend for subjects to have increases in their peripheral 
circulation as measured by the ankle brachial index (ABI). The mean increase in ABI from 
screening to the start of dosing was 0.003. A clinically significant increase in ABI at 3 months 
was observed following dosing (0.15). PDA-002 was safe and well tolerated in these subjects 
who had DFU with PAD. 
Study PDA-002-DFU-002 is a Phase 2, randomized, double blind, placebo-controlled, dose 
range finding study in subjects who have DFU with PAD.  Three doses of PDA-002 (3 x 106, 10 
x 106 and 30 x 106 cells) versus placebo will be evaluated in 2:2:1:2 randomization approach, 
with the lower number of subjects to be allocated to the highest active dose.  Approximately 133 
subjects will be enrolled.  This study is designed as an efficacy and safety study with wound 
closure of the index ulcer within 3 months after dosing and retaining wound closure for the 
subsequent 4 weeks as the primary endpoint.  The study is ongoing, and the data remain blinded. 
Study CCT-PDA-002-DFU-003 is also a Phase 2, randomized, double blind, placebo-controlled 
dose range finding study in 24 subjects who have DFU with PAD. The study is designed to 
assess the safety of repeated monthly IM administration of PDA-002, and to generate the data for 
a clinical proof of mechanism.  The study is investigating 3 monthly doses with PDA-002 dose 
levels (3 x 106 or 30 x 106 PDA-002 cells) on Study Days 1, 29, and 57.  Vascular functional 
parameters as well as potential novel biomarkers will be assessed to predict efficacy and to 
characterize the treatment response in order to evaluate the pharmacodynamics of treatment with 
PDA-002.  The study is ongoing, and the data remain blinded. 
To further evaluate the efficacy and safety of PDA-002, this Phase 2, randomized, double blind, 
placebo-controlled study will enroll 24 subjects with DPN.  The study will employ the same 
doses and dosing schedule of PDA-002 as the aforementioned proof of mechanism study.  The 
primary endpoint of the study is to assess changes in epidermal nerve fiber density (ENFD), an 
indicator of small nerve fiber involvement in DPN (Jacobs, 2011). Symptoms of small fiber 
neuropathy correlate with a decrease in the number, density and length of small nerve fibers in 
the epidermal layer.  Therefore, an increase in ENFD may indicate PDA-002 induced 
neurogenesis. Additionally, since DPN involves both small myelinated and unmyelinated nerve 

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fibers (including those responsible for autonomic function) as well as large nerve fibers, various 
neurophysiological tests are required to identify dysfunction of different nerve populations.  
Therefore, physiological changes, signs, symptoms, and function related to DPN will be 
measured as exploratory endpoints. 
Please refer to the Investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile of 
PDA-002. 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP) 
guidelines, and applicable regulatory requirements. 
 

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2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of the study is to assess the efficacy of PDA-002 versus placebo in 
subjects with DPN, based on the change from baseline in epidermal nerve histology at 6 months.  
2.2. 
Secondary Objective 
The secondary objective of the study is to assess the safety and tolerability of IM administration 
of 2 different doses of PDA-002 or placebo in subjects with DPN. 
2.3. 
Exploratory Objectives 
The key exploratory objectives of the study are to assess any potential treatment effects of IM 
administration of 2 different doses of PDA-002 versus placebo in subjects with DPN as 
measured by changes from baseline in: 
 Epidermal nerve histology at 3 months 
 Lower limb microvascular oxygenation 
 Vascular reactivity  
 DPN signs and symptoms 
 Motor and sensory nerve conduction and autonomic function 
 Health-related quality of life measures 
 Vascular, immune, and/or neural and laboratory parameters 
 Assessment of the systemic versus local efficacy of PDA-002 

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3. 
STUDY ENDPOINTS 
3.1. 
Primary Endpoint 
The primary endpoint of the study is to assess the change from baseline in epidermal nerve fiber 
density (ENFD) at 6 months, an indicator of small nerve fiber involvement, following IM 
administration of 2 different doses of PDA-002 or placebo in subjects with DPN. 
3.2. 
Secondary Endpoint  
The secondary endpoint is to evaluate the safety and tolerability of PDA-002 as measured by the 
type, frequency, severity, and potential relationship of adverse events to treatment with PDA-002 
or placebo. 
3.3. 
Exploratory Endpoints 
Exploratory endpoints of the study include measuring changes from baseline in: 
 ENFD at 3 months 
 Hyperspectral Imaging (HSI) to evaluate lower limb microvasculature oxygenation 
 Vascular Reactivity by Laser Doppler Iontophoresis and Nerve Axon Reflex 
measurements 
 Signs/symptoms of DPN as assessed by the 6-item Neuropathy Total Symptom Score 
(NTSS-6)  
 Signs/symptoms of DPN as assessed by the Neurological Impairment Score of the 
Lower Limb (NIS-LL)  
 Signs/symptoms of DPN as assessed by the Utah Early Neuropathy Scale (UENS)  
 Motor and sensory nerve conduction and autonomic function as evaluated by 
electrophysiologic nerve conduction studies  
 Quantitative Sudomotor Axon Reflex Testing (QSART)  
 Health-Related quality of life (QOL) as measured by the Norfolk QOL-DN  
 Vascular, immune, and/or neuronal and laboratory parameters measured in blood 
and/or epidermal tissues or other biological samples as appropriate  
 Patient Global Impression of Change in Neuropathy (PGICN). 

PDA-002 
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4. 
OVERALL STUDY DESIGN  
4.1. 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, dose range finding study in 
subjects who have DPN.  The study will enroll approximately 24 subjects. Subjects will be 
randomized to receive one of 3 treatments:  PDA-002 (3 x 106 cells), PDA-002 (30 x 106 cells), 
or placebo (vehicle control) in a 1:1:1 randomization approach.  Investigational product or 
placebo will be administered monthly (3 administrations total on Study Days 1, 29, and 57). 
Subjects will be treated and evaluated as indicated in the Table of Events (Table 1).  
Subjects will undergo a Screening Period (up to 28 days in duration) to determine study 
eligibility and baseline levels of signs and symptoms of DPN will be established.  Subjects will 
then enter a Treatment Period (6 months in duration).  During the Treatment Period, subjects will 
be evaluated on an ongoing basis (at 8 scheduled study visits).  Subjects will receive IM 
injections of IP on Study Days 1, 29, and 57 as fifteen 0.30 mL injections (below the knee and 
above the ankle) in one lower extremity in a blinded manner.  After completing the Treatment 
Period, subjects will enter the Follow-up Period where they will continue to be evaluated at 
scheduled study visits over the subsequent months. 
An analysis of all study data will occur after the last subject has completed Visit 9 (Month 6) and 
after the last scheduled study visit. Analyses to be performed can be found in the Statistical 
Analysis Plan. 
The study will be subject to oversight by an independent Data Monitoring Committee (DMC).  
The DMC will review unblinded efficacy and safety data on an ongoing basis (both scheduled 
and ad hoc [if needed]) as outlined in the DMC Charter. 
4.2. 
Study Design Rationale 
Therapies for the treatment of DPN are currently limited to pain relief (tricyclic antidepressants, 
serotonin norepinephrine reuptake inhibitors, anticonvulsants, opioids, and non-prescription 
analgesics). Current treatments do not adequately address the symptoms in a large proportion of 
subjects with DPN, and there are no approved treatments that target the underlying disease.  
One of the major pathophysiologic factors that contributes to DPN is damage to the vasa 
nervorum or the vascular supply to the nerves involved in DPN. In DPN, vascular damage to the 
vasa nervorum is induced by glycosylated proteins interacting with receptors to cells that are 
relevant to the atherosclerotic process, oxidative stress to the vessel wall, and hyperglycemia 
inducing protein kinase C, which is responsible for increased blood vessel permeability, nitric 
oxide dysfunction, and increased leukocyte adhesion (Kles, 2006).   
Results from the rat hind limb ischemia model show that mesenchymal like stromal cells isolated 
from human placenta (formulated for IM injection as PDA-002) have potential clinical use in 
tissue repair through increasing angiogenesis. Furthermore, PDA-002 cells implanted in a mouse 
model of chronic hind limb ischemia improved blood perfusion and limb functional recovery 
(see Investigators Brochure).  

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The assessment of changes in nerve function and microvascular oxygenation in subjects with 
DPN will be based on a combination of evaluations that will assess nerve histology, DPN signs 
and symptoms, and tissue perfusion and oxygenation using measurement methods listed in the 
Table of Events (Table 1). 
With regard to route of administration, IM administration of PDA-002 has demonstrated an 
acceptable safety profile to date. After IM administration in animal models, there was no 
evidence of distribution to the vascular compartment and PDA-002 cells were detected only at 
the site of administration and draining lymph nodes. Care will be taken to avoid systemic 
injection of cells.  
The doses selected for this study are based upon the effective doses adjusted for body weight that 
were administered in the previously described hind limb ischemia (HLI) animal models, as well 
as the dosing in the Phase 1 study PDA-002-DFU-001. Data on the first 3 dose cohorts of the 
Phase 1 study in which subjects were administered 3 x 106 cells, 10 x 106 cells and 30 x 106 cells 
on Days 1 and 8 demonstrated that the doses were well tolerated with no reported dose limiting 
toxicity (DLT). To date based upon the observed safety profile from the Phase 1 study, no new 
risks have been identified for PDA-002 that would preclude dosing in the Phase 2 studies. 
For this study, subjects will be randomized to receive PDA-002 or placebo in one lower 
extremity in a blinded manner. Although PDA-002 is being administered IM, it is unclear if the 
therapeutic effect is localized to the area of injection or systemic. In pre-clinical HLI studies, the 
therapeutic effect of PDA-002 was similar in animals administrated the IM and intravenous (IV) 
formulation. The mechanism of action of PDA-002 is due to a modulation of the immune system 
from a pro inflammatory to anti-inflammatory state that facilitates angiogenesis both in the area 
directly in contact with PDA-002 along with other areas that may be affected by inflammation 
and ischemia. Since DPN causes a symmetrical dysfunction to the nerves of the lower 
extremities, assessments of nerve function as well as changes in neurologic signs will be 
assessed in both legs in order to determine if the therapeutic effect of PDA-002 is local vs. 
systemic.   
The dosing schedule of PDA-002 in this study will be 3 repeated monthly administrations. The 
schedule is based on the safety of 3 repeat IM doses of PDA-002 demonstrated in animal studies. 
Please refer to the Investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and AE profile of PDA-002.  
One additional design feature of this study is that while PDA-002 is injected into one leg, both 
legs are checked for changes in neuropathy signs and symptoms. This will enable determining if 
the effects of PDA-002 on DPN are limited to the area in which the cells are injected, or the 
effect is systemic. 
 
 

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Celgene Corporation 
Protocol CCT-PDA-002-DPN-001 
Celgene Cellular Therapeutics 
Confidential and Proprietary 
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CCT-PDA-002-DPN-001 Amendment 1 Final: 02 Sep 2015 
Figure 1: 
Overall Study Design 
 
Screening Period 
             Treatment Period               Follow-up Period 
Day -28 to Day -1 
 
 Day 1 to Day 186                  Day 187 to Day 425 
 
 
 
 
 
 
 
 
4.3. 
Study Duration 
Subjects are expected to participate in the study from screening (up to Day -28) to 1 year after 
the last IP injection. 
Subjects will undergo a Screening Period of up to 28 days.  During the Screening Period 
eligibility will be confirmed and baseline assessments will be performed.  Subjects will then 
enter a 6 month Treatment Period consisting of 8 scheduled study visits.  During the Treatment 
Period, IP or placebo will be administered on Study Days 1, 29, and 57, and efficacy and safety 
evaluations will be performed.  Following this, subjects will then enter a Follow-up Period.  The 
Follow up Period will consist of scheduled bi-monthly study visits to continue to assess safety 
and longer-term efficacy. 
4.4. 
End of Trial 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date. 
 
ICF signature and 
eligibility screening  
 
Randomized  
double-blind, 
placebo-controlled 
Treatment days 
1,29,57 
1:  3 x 106 cells  
Follow-up 
visits months 
8,10,12, 
15 

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5. 
TABLE OF EVENTS 
Table 1: 
Table of Events 
Event 
Screening
Period 
Treatment Period 
Follow-up Period 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Day 
-28 to Day 
0 
Day 1 
(±3 
days)
Day 
15 
(±3 
days) 
Day 
29 
(±3 
days) 
Day 57
(±3 
days) 
Day 
93 
(±7 
days) 
Day 
120 
(±3 
days)  
Day 
155 
(±3 
days) 
Day 
186 
(±7 
days) 
Day 
246  
(±7 
days) 
Day 
306 
(±7 
days) 
Day 
365 
(±7 
days) 
Day 
425 
(±7 
days) 
Early 
Termin-
ation 
 
Week 
1 
Week 
2 
Month 
1 
Month 
2 
Month 
3 
Month 
4 
Month 
5 
Month 
6 
Month 
8 
Month 
10 
Month 
12 
Month 
14 
 
Informed consent 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Inclusion/exclusion criteria 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Demography/medical and surgical history 
including duration of diabetes and diabetic 
peripheral neuropathy 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Prior/concomitant medication and 
procedures  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination including vital signs 
(height [at Visit 1 only], weight, body 
temperature, blood pressure, respiration, 
and pulsea 
X 
X 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead electrocardiogram (ECG)f 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Clinical laboratory testing (serum 
biochemistry, hematology, coagulation 
tests urinalysis). Estimated glomerular 
(eGFR) filtration rate will be calculated 
(Screening). 
X 
X 
- 
X 
X 
- 
- 
- 
X 
- 
- 
- 
X 
X 
Anti-HLA antibodies 
X 
Xe 
- 
Xe 
Xe 
X 
- 
- 
- 
- 
- 
- 
- 
- 
HbA1c testing 
X 
- 
- 
- 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Obtain blood for exploratory biomarker 
evaluation prior to administration of IPb  
X 
X 
- 
X 
X 
X 
- 
- 
X 
- 
- 
- 
- 
X 

PDA-002 
Celgene Corporation 
Protocol CCT-PDA-002-DPN-001 
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Confidential and Proprietary 
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CCT-PDA-002-DPN-001 Amendment 1 Final: 02 Sep 2015 
 
Table 1: 
Table of Events (Continued) 
Event 
Screening
Period 
Treatment Period 
Follow-up Period 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Day 
-28 to Day 
0 
Day 1 
(±3 
days)
Day 
15 
(±3 
days) 
Day 
29 
(±3 
days) 
Day 57
(±3 
days) 
Day 
93 
(±7 
days) 
Day 
120 
(±3 
days)  
Day 
155 
(±3 
days) 
Day 
186 
(±7 
days) 
Day 
246  
(±7 
days) 
Day 
306 
(±7 
days) 
Day 
365 
(±7 
days) 
Day 
425 
(±7 
days) 
Early 
Termin-
ation 
 
Week 
1 
Week 
2 
Month 
1 
Month 
2 
Month 
3 
Month 
4 
Month 
5 
Month 
6 
Month 
8 
Month 
10 
Month 
12 
Month 
14 
 
 Pregnancy testc 
X 
X 
- 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
X 
Retinal examination 
X 
- 
- 
- 
- 
- 
- 
- 
X 
- 
- 
X 
- 
X 
6 Item Neuropathy Total Symptom Score 
(NTSS-6) 
X 
- 
- 
X 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Utah Early Neuropathy Scale (UENS) 
X 
- 
- 
X 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Neuropathy Impairment Score of the 
Lower Limb (NIS-LL) 
X 
- 
- 
X 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Electrophysiologic nerve conduction 
studies  
X 
- 
- 
- 
- 
- 
- 
- 
X 
- 
- 
X 
- 
X 
Hyperspectral imaging 
X 
- 
- 
X 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Quantitative Sudomotor Axon Reflex 
Testing (QSART)  
X 
- 
- 
- 
- 
- 
- 
- 
X 
- 
- 
X 
- 
X 
Skin biopsies 
X 
- 
- 
- 
- 
X 
- 
- 
X 
- 
- 
- 
- 
- 
Histology of Immune Cells (mast cell) 
X 
- 
- 
- 
- 
X 
- 
- 
X 
- 
- 
- 
- 
- 
Norfolk Quality of Life Assessment 
(Norfolk-QOL-DN) 
X 
- 
- 
- 
- 
X 
- 
- 
X 
- 
- 
X 
- 
X 
Patient Global Impression of Change in 
Neuropathy (PGICN) 
X 
X 
X 
X 
X 
- 
- 
- 
X 
- 
- 
X 
- 
X 
 

PDA-002 
Celgene Corporation 
Protocol CCT-PDA-002-DPN-001 
Celgene Cellular Therapeutics 
Confidential and Proprietary 
25 
CCT-PDA-002-DPN-001 Amendment 1 Final: 02 Sep 2015 
 
Table 1: 
Table of Events (Continued) 
Event 
Screening
Period 
Treatment Period 
Follow-up Period 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Day 
-28 to Day 
0 
Day 1 
(±3 
days)
Day 
15 
(±3 
days) 
Day 
29 
(±3 
days) 
Day 57
(±3 
days) 
Day 
93 
(±7 
days) 
Day 
120 
(±3 
days)  
Day 
155 
(±3 
days) 
Day 
186 
(±7 
days) 
Day 
246  
(±7 
days) 
Day 
306 
(±7 
days) 
Day 
365 
(±7 
days) 
Day 
425 
(±7 
days) 
Early 
Termin-
ation 
 
Week 
1 
Week 
2 
Month 
1 
Month 
2 
Month 
3 
Month 
4 
Month 
5 
Month 
6 
Month 
8 
Month 
10 
Month 
12 
Month 
14 
 
Vascular reactivity measurements-
(including Laser Doppler Iontophoresis 
and Nerve Axon Reflex measurements) 
X 
- 
- 
- 
- 
X 
- 
- 
X 
- 
- 
X 
- 
- 
Administration of IP  
- 
X 
- 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
IP administration monitoring (including 
visual inspection of injection areas, vital 
signs, and collection of blood for 
coagulation tests and tryptase/histamine 
evaluation before and after IP 
administration) 
- 
X 
- 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Assess and record adverse eventsd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: IP=Investigational Product, PBMC=peripheral blood mononuclear cell, RBC=red blood cell, SAE=serious adverse event. 
a Physical exams during the Screening Period and Early Termination will be full physical examinations. At all other assessments, physical examinations should only be directed to 
evaluate reported adverse events.  Assessments for vital signs can be performed within15 minutes for the 1 and 2 hour post dose assessments. 
b Biomarkers assessed at Screening, Visit 2 Day 1 and Visit 4 Day 29, and Visit 5 Day 57 prior to injection of IP.  Biomarkers will also be assessed on Day 93 when there is no IP 
injection.  Biomarker samples will include blood immune biomarkers and RBC-lysed PBMC sample for the chip cytometry assay.  The chip cytometry assay will only be 
performed at selected sites. 
c Serum pregnancy testing at Screening and urine pregnancy testing at all other visits of females of childbearing potential.  At Visit 2 a urine pregnancy needs to be performed if a 
serum pregnancy test was not done within 0-72 hours predose.  Prior to treatment on Study Days 1, 29, and 57. 
d Adverse events will be followed for 28 days after the last dose of IP.  SAEs will be followed until the last study visit. 
e Prior to injection on Days 1, 29 and 57. 
f  If performed within 28 days of signing the informed consent it does not need to be repeated. 
 
 

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Confidential and Proprietary 
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6. 
PROCEDURES 
6.1. 
Study Entry/Screening Period (Visit 1) 
Visit 1 and Visit 2 can occur up to 28 days apart.  All Screening Period procedures should be 
performed as per Table 1. 
Informed Consent/Previous Participation:  The initial screening visit will occur up to 28 days 
prior to the initial administration of IP.  Before or at Visit 1, qualified site personnel will explain 
the study to the subject, answer all of his/her questions, and obtain written informed consent/ 
Health Insurance Portability and Accountability Act (HIPAA) authorization before performing 
any study-related procedures.  A copy of the signed informed consent will be given to the 
subject, and the date of the signing of the informed consent will be recorded in the electronic 
case report form (eCRF) and in the source documents.  Previous participation in any other 
CCT-PDA study will be recorded in the eCRF and in the source documents. 
Assessment of Adverse Events:  Adverse events (AEs) will be collected from the time the 
subject signs the informed consent throughout the study.  The type, frequency and severity of 
adverse events and potential relationship to IP will be collected as described in the full study 
protocol. 
Demographics/Medical and Surgical History: Demographics and medical history will be 
obtained during screening.  Demographics will include subject’s initials, date of birth, sex, 
ethnicity, and race.  A thorough medical and surgical history including date of diagnosis of DM 
and DPN, psychiatric conditions, current medical conditions, and any known allergies will be 
performed.   
Prior/Concomitant Medications:  All medications taken (including contraception measures) 
within the last 35 days should be recorded.  All medications that a subject is currently taking will 
also be recorded from the time the subject signs the informed consent throughout the study.   
Physical Examination/Vital Signs:  Subjects will undergo a routine physical examination.   
Vital signs including height (cm) (Visit 1 only), weight, (kg) body temperature (°C), pulse 
(beats/minute), respiration (breaths/minute), and resting systolic and diastolic blood pressure 
(mmHg) will be measured and recorded in the eCRF and in the source documents.   
Pregnancy Testing 
Serum pregnancy testing at Screening and urine pregnancy testing at all other visits of females of 
childbearing potential.  At Visit 2 a urine pregnancy needs to be performed if a serum pregnancy 
test was not done within 0-72 hours predose. Pregnancy testing will be conducted prior to 
treatment on Study Days 1, 29, and 57. 
Electrocardiogram:  A 12-lead ECG will be obtained.  At screening, if a 12-lead ECG was 
performed as part of the subject’s previous routine care within 28 days prior to signing of the 
informed consent, it does not need to be repeated.  The following will be recorded in the eCRF 
and in the source documents: 
Any ECG finding that is judged by the investigator as a clinically significant change (worsening) 
compared to a baseline value will be considered an AE and will be recorded and monitored. 

PDA-002 
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Confidential and Proprietary 
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Clinical Laboratory Tests:  Blood and urine samples for routine laboratory testing as well as 
blood for exploratory biomarker analysis will be obtained as per the Table of Events (Table 1) 
and will be evaluated by a central laboratory.  Please refer to the Laboratory Manual for detailed 
information on the collection, storage, and shipment of laboratory samples. 
Serum Chemistry 
Serum chemistry will be assessed at all visits as indicated in the Table of Events (Table 1) and 
will include the following: 
 Calcium 
 Total Bilirubin 
 Chloride 
 Indirect Bilirubin 
 Potassium 
 Direct Bilirubin 
 Sodium 
 Glucose 
 Phosphorus 
 Bicarbonate or Carbon Dioxide 
 Uric acid 
 Lactic Dehydrogenase (LDH) 
 Alanine Aminotransferase (ALT; 
SGPT) 
 Alkaline Phosphatase (ALK) 
 Aspartate Aminotransferase (AST; 
SGOT) 
 Total Protein 
 Creatinine 
 Albumin 
 Blood Urea Nitrogen (BUN) 
 
Hematology 
Hematology tests will be performed at all visits as indicated in the Table of Events (Table 1) and 
will include the following:  
 Hemoglobin 
 Hematocrit 
 Red Blood Cell (RBC) Count  
 Platelet Count 
 Absolute Neutrophil Count (ANC) 
 White Blood Cell (WBC) Count 
and Differential Count 

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Urinalysis 
Urinalysis will be performed at visits indicated in the Table of Events (Table 1) and will include 
the following: 
Urine albumin and creatinine to be collect with the morning void 
 Protein 
 Glucose 
 Ketones 
 Blood (hemoglobin) 
 pH 
 Specific Gravity 
 Microscopic (if gross findings are 
positive, then a microscopic 
examination, including WBCs/high 
power field (HPF) and RBCs/HPF, 
will be performed). 
 Bilirubin  
 Urinary Albumin 
 Creatinine 
 Leukocyte Esterase 
Immunological/Inflammation Assessments 
Immunological/inflammation assessment will include the following testing:  
 Anti-HLA antibodies as indicated in the Table of Events (Table 1). 
 
Hemoglobin A1c 
Hemoglobin A1c will be measured as indicated in the Table of Events (Table 1).  
Coagulation Tests 
Coagulation tests including assessment of PT/PTT, D-dimers, fibrinogen, and platelets will be 
assessed as indicated in the Table of Events (Table 1) prior to dosing with IP and approximately 
2 hours post-dose.  Assessments can be performed within 1 hour of the 2 hour post dose time 
frame.  
Tryptase and Histamine 
Tryptase and histamine levels will be assessed on the day of treatment prior to dosing with IP 
and approximately 2 hours postdose as indicated in the Table of Events (Table 1).  
Exploratory Biomarkers 
Exploratory biomarkers will be measured as indicated in the Table of Events (Table 1). 
Skin Biopsies:  Two 3mm thickness skin punch biopsies will be taken at the lateral aspect of the 
distal legs (2 biopsies; 1 per leg) approximately 10 cm above the lateral malleolus, and two 
biopsies will be taken at the volar aspect of the forearm (2 biopsies on 1 forearm).  Instructions 
for tissue collection, handling, and shipping instructions are located in the Laboratory Manual.  

PDA-002 
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Confidential and Proprietary 
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Contraception:  Females of childbearing potential1 must use adequate contraception for the 
duration of their participation in the study (which includes 28 days prior to starting IP, during the 
Treatment Period [including dose interruptions], and during the Follow-up Period).  Adequate 
contraception is defined as the simultaneous use of 2 of the following forms of contraception 
methods: oral, injectable or implantable hormonal contraception; tubal ligation; intrauterine 
device (IUD); barrier contraceptive with spermicide; or a vasectomized partner. 
Males (including those who have had a vasectomy) must agree to use barrier contraception (latex 
condoms) when engaging in sexual activity with females of child bearing potential (FCBP) for 
the duration of their participation in the study, including the Follow-up Period. 
Retinal Assessment:  Retinal assessment conducted by an ophthalmologist or optometrist will 
be performed and scored using the International Clinical Diabetic Retinopathy Disease Severity 
Scale (Appendix B).  Results will be recorded in the eCRF and in the source documents. 
6-Item Neuropathy Total Symptom Score (NTSS-6):  To be completed as outlined in Efficacy 
Procedures Section 6.4. 
Neurological Impairment Score of the Lower Limb (NIS-LL):  To be completed as outlined 
in Efficacy Procedures Section 6.4. 
Utah Early Neuropathy Scale (UENS):  To be completed as outlined in Efficacy Procedures 
Section 6.4. 
Nerve Conduction Studies:  To be completed as outlined in Efficacy Procedures Section 6.4. 
Quantitative Sudomotor Axon Reflex Testing (QSART):  To be completed as outlined in 
Efficacy Procedures Section 6.4. 
Norfolk QOL-DN:  To be completed as outlined in Efficacy Procedures Section 6.4.  
Patient Global Impression of Change in Neuropathy (PGICN):  To be assessed as outlined in 
Efficacy Procedures Section 6.4.  
Vascular Reactivity Measurements*:  To be completed as outlined in Efficacy Procedures 
Section 6.4.   
*This procedure will only be measured if it is available for this study protocol at the 
participating site. 
Hyperspectral Imaging (HSI)*:  To be completed as outlined in Efficacy Procedures Section 
6.4.   
* This procedure will only be performed if it is available for this study protocol at the participating site. 
Final Review of All Inclusion/Exclusion Criteria:  The investigator or designee will review all 
inclusion/exclusion criteria once the subject has completed all screening assessments.  If the 
subject meets all of the study entrance criteria, the subject will be randomized and scheduled for 
dosing with IP.  Study site personnel will contact the Interactive Web Response System (IWRS) 
                                                 
1 A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the 
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been 
postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 
consecutive months).Tubal ligation is not sufficient for non-child bearing potential. 

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for each subject’s treatment group assignment, and the randomization number will be recorded in 
the eCRF and in the source documents. 
6.2. 
Treatment Period (Visit 2 through Visit 9) 
Visit 2 through Visit 9 should occur on the days specified within the allowable variance.  All 
Treatment Period procedures should be performed as per Table 1. 
Administration of IP (Visit 2, Visit 4, and Visit 5) 
IP will be administered on Study Days 1, 29 and 57.  Preparation and administration of IP is 
discussed in Section 8.2. 
IP Administration Information:  IP thaw time, start and stop time of injections, and 
administration interruption/completion will be recorded in the eCRF and in the source 
documents. 
IP Administration Vital Signs:  Vital signs including heart rate, respiration, blood pressure, and 
body temperature will be monitored prior to starting the injections and at 1 and 2 hours after 
completion of the injections (± 15 minutes). 
IP Administration Additional Blood Sampling:  Blood samples for tryptase and histamine, 
coagulation assessments (PT/PTT), and exploratory biomarkers will be collected 2 hours before 
(± 15 minutes) IP administration and also at 2 hours after IP administration for tryptase and 
histamine assessments as indicated in the Table of Events (Table 1).  
IP Administration Adverse Event Monitoring:  A visual inspection of injection sites will be 
conducted periodically from the initial injection until 2 hours after the last injection (minimum).  
Any clinically significant findings will be recorded as AEs in the eCRF and in the source 
documents.   
6.3. 
Follow-Up Period 
All subjects will be followed for 28 days after the last dose of IP for AE reporting, as well as 
SAEs that will be followed until the last study visit and made known to the investigator at any 
time thereafter that are suspected of being related to IP, as described in Section 11.1.  
The Follow-up Period will take place from Visit 10 through Visit 13 and include Early 
Termination. Visits should occur on the day specified ± 3 days or ± 7 days as specified in the 
Table of Events (Table 1).  
All other procedures (as discussed in Section 6.1 and Section 6.2) will be conducted as per the 
Table of Events (Table 1). 
6.4. 
Efficacy Procedures 
The following efficacy assessments will be performed as outlined in the Table of Events 
(Table 1). 
Epidermal Nerve Fiber Density (ENFD):  This assessment relies on an immunohistochemical 
localization of a neural antigen within axons.  Histological specimens will consist of serial 3mm 
thickness punch biopsies of the epidermis taken bilaterally at the lateral aspect of the distal legs.  
To quantify ENFD (fibers/mm of epidermis), the pathologist manually counts the number of 

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epidermal nerve fibers in 3 to 5 sections and divides the value by the lengths of the epidermal 
specimens in millimeters.  In addition, a quantification of the autonomic sudomotor (sympathetic 
cholinergic) and pilomotor (sympathetic adrenergic) nerve fibers will be conducted within the 
same biopsy. 
Histology of Immune Cells:  Two skin biopsies will be taken from the volar aspect of the 
forearm.  The first biopsy will be used for histology analysis to evaluate the inflammatory 
response by assessing inflammatory cell infiltration.  The second biopsy will be used to perform 
mRNA / protein analysis.  
Circulating Blood Biomarkers:  Blood collected to be used for biomarker analysis will include 
whole blood collection for blood immune biomarkers and red blood cell (RBC)-lysed peripheral 
blood mononuclear cell (PBMC) sample for the chip cytometry immune phenotyping assay*.   
* These assessments for RBC-lysed peripheral blood mononuclear cell (PBMC) by the 
chip cytometry assay will only be performed at selected sites. 
Hyperspectral Imaging *:  Hyperspectral imaging (HIS) obtains multiple images at discrete 
wavelengths, providing a diffuse reflectance spectrum of each pixel in the image. The system 
uses wavelengths between 500 and 600 nanometers which serve to obtain oxy- and deoxy-
hemoglobin absorption peaks.  Tissue oxygenation images or “maps” are then constructed from 
oxy- and deoxy-hemoglobin values determined from each pixel in the image.  HSI will be 
measured in both lower limbs. 
*This procedure will be measured only if it is available for this study protocol at the 
participating site. 
6-item Neuropathy Total Symptom Score (NTSS-6):  The NTSS-6 questionnaire is used to 
evaluate the frequency and intensity of neuropathy sensory symptoms identified by subjects with 
DPN (ie, numbness and/or insensitivity, prickling, and/or tingling; burning pain; aching pain 
and/or tightness, sharp shooting lancinating pain and allodynia and/or hyperalgesia).  Symptoms 
are graded based on the experience of the subject during the past 24 hours.  Each symptom 
question can be assigned a maximum score of 3.66 points.  The symptom scores are summed, 
and the total score can range from 0 points to 21.96 points.  A higher score indicates greater 
disability. 
Neurological Impairment Score of the Lower Limb (NIS-LL):  The NIS-LL is an assessment 
tool composed of a sensory subscore (which evaluates sensory perceptions to touch, prickling 
pain, vibration, joint position, and to 1 gram and 10 gram monofilaments), and a motor subscore 
(which evaluates muscle strength, muscle wasting, and deep tendon reflexes) in the lower limbs.  
The scale is additive for all deficits and is applied in a bilateral manner for each modality tested.  
The subscores are totaled and can range from 0 points (normal neurological function) to 88 
points (absence of all motor, sensory, and reflex activity).  An increase of 2 points is clinically 
significant. 
Utah Early Neuropathy Scale (UENS):  The UENS uses a physical examination specific to 
early sensory predominant polyneuropathy which emphasizes severity and spatial distribution of 
sharp sensory loss in the foot and leg.  The total score can range from 0 to 42.  A higher score 
indicates greater disability. 

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Electro physiologic Nerve Conduction Studies:  Nerve conduction studies allow for the 
quantification of the conduction amplitude, velocity, and latency of the tibial and peroneal 
nerves, and the amplitude and latency of the sural nerve.  Reduction of amplitudes of recorded 
responses generally indicates a loss of axons. Nerve conduction will be measured in both lower 
limbs.  
Quantitative Sudomotor Axon Reflex Testing (QSART):  QSART is a measurement of 
autonomic involvement by evaluating postganglionic sudomotor function deficits in the foot, 
distal leg, and distal thigh.   
Patient Global Impression of Change in Neuropathy (PGICN):  The PGICN is a subject’s 
self assessment to describe and change in symptoms of neuropathy such as pain, tingling, or 
numbness. 
Health-Related Quality of Life (QOL) as measured by the Norfolk QOL-DN:  The Norfolk 
QOL-DN is composed of 5 domains (physical functioning/large fiber neuropathy, activities of 
daily living, symptoms, small fiber neuropathy, and autonomic nerve function) encompassing 35 
scored questions related to subjects’ neuropathy signs and symptoms, as well as to the impact of 
DPN on subjects’ activities of daily life.  The total score can range from -2 to 138.  A higher 
score indicates higher disability. 
Vascular Reactivity Measurements*:  Vascular reactivity will be measured by using Laser 
Doppler Iontophoresis and Nerve Axon Reflex measurements in both lower limbs.  By applying 
acetylcholine chloride, the endothelium-dependent vasodilatation may be measured.  The MIC1 
iontophoresis system will be used in this study.  Specifically, a small quantity (<1 ml) of 1% 
acetylcholine chloride solution will be used on the forearm of the participating subjects; 
subsequently a constant current of 200 microampere will be applied for 60 seconds achieving a 
dose of 6 mC.cm-2.  The single spot reaction will be measured by Laser Doppler Flowmetry 
using a DRT4 Laser Doppler Blood Flow Monitor. 
The Nerve Axon Reflex measurement will be performed at the foot level by using a single point 
Laser Probe during the acetylcholine iontophoresis.  The single spot reaction will be measured 
by Laser Doppler Flowmetry using a DRT4 Laser Doppler Blood Flow Monitor.  The probe will 
be attached to the center of the iontophoresis chamber.  As the probe is not in direct contact with 
the foot, it will only measure the nerve axon-related vasodilation.  The results are expressed as 
percentage of increase over the baseline blood flow. 
*This procedure will be measured only if it is available for this study protocol at the 
participating site. 
6.5. 
Safety 
Safety will be assessed by an ongoing review of clinical laboratory tests (hematology, serum 
chemistry, coagulation, pregnancy, urinalysis, physical examination results, vital sign 
measurements, 12-lead ECG at screening only, weight, use of concomitant 
medications/procedures, and the incidence and severity of injection site and injection-related 
reactions (including tryptase and histamine) and treatment-emergent AEs. 

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6.5.1. 
External Data Monitoring Committee 
An external unblinded DMC will monitor safety and efficacy information to ensure subject 
safety in accordance with a separate charter.  The external DMC will be comprised of members 
who are not involved in the day-to-day activities of the PDA-002 DPN study team.  Data review 
packets will be forwarded to the DMC members for review at least 7 days prior to each 
scheduled DMC teleconference/meeting.  Data will be current through 14 days prior to each 
scheduled DMC teleconference/meeting. 
The external DMC will be convened to assess the benefit risk of PDA-002 when approximately 
25% and 50% of subjects complete the Month 3 (Visit 6) assessment. Study enrollment will be 
ongoing during these scheduled reviews. 
The external DMC chairman will be notified if an AE of medical interest should occur and will 
determine if a full DMC will need to be conveyed. During any period of deliberation by the 
external DMC on an AE of medical interest, a temporary hold on enrollment of new subjects will 
be instituted. The AEs of medical interest that would trigger this process are: 
 Identification of 1 or more subjects within a dosing treatment arm with ≥ Grade 3 
allergic reaction that is suspected to be related to the IP.  
 Identification of 1 or more subjects experiencing a suspected unexpected, treatment-
related SAE (SUSARs) within 14 days following the initial dose of the IP suspected 
unexpected serious adverse reactions.  
 Identification of 1 or more subjects with a new malignancy.  
The sponsor will take appropriate action based upon the external DMC recommendation and this 
will be communicated to the investigators.  The investigators will be responsible for notifying 
their Institutional Review Boards (IRBs).  The external DMC will evaluate on an ongoing basis 
all available safety data, in particular all SAEs and their potential relationship to PDA-002.  The 
external DMC may recommend modifications to enrollment or to the study design in order to 
ensure subject safety.  Further explanation of the roles and responsibilities of the external DMC 
will be outlined in the external DMC charter. 
 

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7. 
STUDY POPULATION 
7.1. 
Number of Subjects and Sites 
Approximately 24 subjects with diabetic peripheral neuropathy will be enrolled at about 5 sites 
in the United States. 
7.2. 
Inclusion Criteria 
Subjects must satisfy the following criteria to be enrolled in the study 
1. Males and females who are at least 18 years of age at the time of signing the informed 
consent document. 
2. Subject must understand and voluntarily sign an informed consent document prior to any 
study related assessments/procedures are conducted.  
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements  
4. Diabetes mellitus (DM) Type 2 as defined by the ADA or WHO criteria (Appendix A). 
5. Meet established criteria for DPN due to Type 2 diabetes with the following: 
a. Abnormal symptoms (NTSS-6 ≥ 6 points (total score) or ≥ 2.0 points for one or 
more symptoms) 
AND 
b. Abnormal signs (UENS score of 2-24 and/or NIS-LL score of 2-10). 
6. A female of childbearing potential must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test prior to treatment with study therapy.  In 
addition, sexually active Females of Child Bearing Potential (FCBP) must agree to use 2 
of the following adequate forms of contraception methods simultaneously such as: oral, 
injectable, or implantable hormonal contraception, tubal ligation, IUD, barrier 
contraceptive with spermicide or vasectomized partner for the duration of the study.  
7. Males (including those who have had a vasectomy) must agree to use barrier 
contraception (latex condoms) when engaging in sexual activity with FCBP for the 
duration of the study. 
7.3. 
Exclusion Criteria 
The presence of any of the following will exclude a subject from enrollment: 
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that 
would prevent the subject from participating in the study. 
2. Other causes of neuropathy in diabetic subjects: chronic inflammatory demyelinating 
polyneuropathy; neuropathy due to vitamin B12 deficiency, hypothyroidism, and uremia 
syndrome; and neuropathy due to entrapment or trauma.  

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3. A reversible course of acute painful diabetic neuropathy syndrome: treatment-induced 
diabetic neuropathy that presents in the setting of rapid glycemic control; diabetic 
neuropathic cachexia; and diabetic anorexia, a diabetic neuropathy that is seen with 
intentional weight loss.  
4. History of a prior diagnosis of severe peripheral arterial disease (PAD).  
5. Thrombocytopenia and coagulopathy, to avoid severe bruising or bleeding due to 
multiple intramuscular (IM) injections.  
6. Any condition including the presence of laboratory abnormalities that places the subject 
at unacceptable risk if he or she were to participate in the study. 
7. Any condition that confounds the ability to interpret data from the study. 
8. Subjects who are taking opioids for the treatment of DPN.  
9. Pregnant or lactating females.  
10. Subjects with a body mass index > 40 kg/m2 at screening. 
11. Neuropathy resulting from a condition other than DM and/or significant co-morbid 
neurological diseases (eg, Parkinson’s disease, epilepsy, multiple sclerosis, alcoholic 
peripheral neuropathy), or exposure to agents suspected to cause symptoms of neuropathy 
(such as but not limited to metronidazole, antituberculosis medications, and heavy 
metals). 
12. Advanced neuropathy as measured by the absence of sural sensory nerve action potential, 
or a UENS>24 and or a NIS-LL>10. 
13. History of a prior diagnosis of Critical Limb Ischemia.   
14. History of diabetic foot ulceration (at any time) and/or or undergoing a limb 
revascularization procedure(s) and/or amputation(s) due to DM. 
15. Diagnosis of Type 1 DM and/or any of the following:  diagnosis of DM prior to age 35 
years; insulin required to treat DM within 1 year after DM diagnosis; history of diabetic 
ketoacidosis.  
16. AST, ALT, or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) at screening. 
17. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at Screening calculated 
using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history 
of an abnormal eGFR < 60 and decline > 15 mL/min/1.73 m2 below normal in the past 
year. 
18. Bilirubin level > 2 mg/dL (unless subject has known Gilbert’s disease) at screening. 
19. Untreated chronic infection or treatment of any infection with systemic antibiotics within 
4 weeks prior to dosing with IP.   
20. Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic 
blood pressure > 180 mmHg during screening at 2 independent measurements taken 
while subject is sitting and resting for at least 5 minutes).   

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21. History of significant cardiac disorders including but not limited to malignant ventricular 
arrhythmia, CCS Class III-IV angina pectoris, myocardial infarction/ percutaneous 
coronary intervention (PCI) / coronary artery bypass graft (CABG) in the 6 months prior 
to signing the informed consent ICF, pending coronary revascularization in the following 
3 months, transient ischemic attack/cerebrovascular accident in the 6 months prior to 
signing the informed consent form, and/or New York Heart Association [NYHA] Stage 
III or IV congestive heart failure (Appendix C).  Note:  Stable Canadian Cardiovascular 
Society (CCS) Class I-II angina is allowed (Appendix D). 
22. Poorly controlled DM (hemoglobin A1c > 10%) at screening.  
23. Untreated proliferative retinopathy at screening. 
24. Life expectancy less than 2 years due to concomitant illnesses.  
25. History of malignancy within 5 years except for the following circumstances: basal cell 
or squamous cell carcinoma of the skin, remote history of cancer now considered cured 
or positive Pap smear with subsequent negative follow-up. 
26. History of hypersensitivity to any of the components of the product formulation 
(including bovine or porcine products, dextran 40, and dimethyl sulfoxide [DMSO]).   
27. Subject has received an investigational agent —an agent or device not approved by the 
US Food and Drug Administration (FDA) for marketed use in any indication— within 90 
days (or 5 half-lives, whichever is longer) prior to treatment with study therapy or 
planned participation in another therapeutic study prior to the completion of this study or 
has received previous gene or cell therapy at any time. 

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8. 
DESCRIPTION OF STUDY TREATMENTS 
8.1. 
Description of Investigational Product 
PDA-002 is characterized as a cellular angiogenic and immune modulating agent with 
therapeutic potential.  The product contains a mesenchymal-like cell population derived from 
normal, full-term human placental tissue.  The cells are culture-expanded as a plastic-adherent, 
undifferentiated in vitro cell population that expresses the nominal phenotype CD34-, CD10+, 
CD105+, and CD200+.  The cells constitutively express moderate levels of HLA Class I and 
undetectable levels of HLA Class II. 
These cells demonstrate a range of potential biological activities which include the ability to (1) 
induce endothelial cell survival, migration and tube formation, showing angiogenic and 
cytoprotective potential, and (2) modulate T-cell repertoire and affect the M1/M2 balance of 
macrophages demonstrating an immune modulatory effect.  Based on these properties, the 
proposed study will evaluate the safety of PDA-002 in subjects with DPN. 
PDA-002 or placebo (vehicle control) units will be shipped to the study sites as cryopreserved 
units and will be thawed and filled into syringes prior to IM injection.  A PDA-002 unit are 
supplied at 2 dosage strengths and contains approximately 3 or 30 million cells in 4.5 mL of a 
5.75% dextran 40/10% human serum albumin (HSA) solution containing 2.5% DMSO for 
cryopreservation.  The solution also contains Plasma-Lyte and saline to maintain the cells’ 
osmotic environment.  Placebo (vehicle control) units contain the above-mentioned components, 
without any cells. The product is intended for allogeneic use. 
8.2. 
Treatment Administration and Schedule 
Investigational product (IP) will be administered on Study Days 1, 29 and 57.  Thawing of the IP 
should not begin until it is confirmed that the subject meets the inclusion/exclusion criteria.  
Investigational product thawing will be performed by qualified site personnel according to the 
instructions in Appendix E.  Three 3 mL syringes will each be filled with 1.5 mL of IP, and then 
capped.  Syringes will be masked to preserve blinding, and transferred to the personnel 
administering the injections. 
Subjects will receive IP administered as fifteen 0.30 mL injections (approximately 4.5 mL total) 
in one leg.  The target region is suggested to be below the knee and above the ankle.  Injections 
are suggested to be at least 1 cm apart horizontally and laterally and at a depth of approximately 
1 to 4 cm.  It is suggested that they be administered in a pattern of 3 x 5 injections around the leg, 
and injections should not be near a blood vessel. The administrator will be blinded to treatment.  
PDA-002 is not intended for intravenous administration.  When the injection is given, the syringe 
should be aspirated to avoid inadvertent venous administration.  If any blood is aspirated into the 
syringe, the needle is to be pulled out a little, and the syringe re-aspirated.  If no blood is seen, 
the IP may be injected. 
Vital signs (including heart rate, respiration, blood pressure, body temperature) will be 
monitored prior to starting the injections and at 1 and 2 hours (± 15 minutes) after completion of 

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the injections.  Blood samples for tryptase and histamine, coagulation assessments, and 
exploratory biomarkers will be collected as indicated in the Table of Events (Table 1). 
The investigational centers must also offer appropriate supplemental services that support 
clinical care to ensure that the protocol specified IP administration and monitoring will be 
followed. 
Administration Instructions.  Under aseptic conditions, PDA-002 or placebo will be injected 
IM at 15 sites in one limb on Study Days 1, 29, and 57.  The injection volume will be 0.30 mL 
per injection site.  A 3.0 mL syringe with a 20 to 22-gauge 1.5-inch long needle will be used to 
inject the IP.  The target region is suggested to be below the knee and above the ankle.  
Injections are suggested to be at least 1 cm apart horizontally and laterally and at a depth of 
approximately 1 to 4 cm.  It is suggested that they be administered in a pattern of 3 x 5 injections 
around the leg, and injections should not be near a blood vessel. The administrator and the 
subject will be blinded to treatment.  
A diagram of the recommended injection grid and anatomical site selection is provided in 
Appendix E. 
The entire thawed IP must be administered within 4 hours of thaw start time and within 1 
hour of the syringe fill time.  In the event that it becomes medically necessary to stop the 
injections, the stop time of the injections as well as the time the injections are resumed must be 
noted in the eCRF and in the source documents.  If less than the total injection volume is 
administered, the volume injected should be recorded and the sponsor should be notified. 
Note:  For this study, all ≥ Grade 3 allergic reactions associated with the use of IP must be 
reported to Celgene Cellular Therapeutics as an SAE within 24 hours of the investigator’s 
knowledge of the event. 
8.2.1. 
Discontinuation 
The reason for discontinuation should be recorded in the eCRF and in the source documents. The 
decision to discontinue a subject remains the responsibility of the treating physician, which will 
not be delayed or refused by the sponsor. However, prior to discontinuing a subject, the 
investigator may contact the Medical Monitor and forward appropriate supporting documents for 
review and discussion.  Of note, the investigator is not required to contact a medical monitor to 
discuss discontinuation or unblinding as the investigator has the ability to discontinue or rapidly 
unblind subjects. 
Subjects who discontinue will have the procedures performed as listed in the Early Termination 
column as per the Table of Events (Table 1). 
8.2.2. 
Overdose 
An overdose is defined for this protocol as a subject receiving any dose of greater than 30 x 106 
cells in a 24 hour period.  Adverse events associated with an overdose must be collected as an 
Adverse Event as outlined in Section 11.2. Evaluation of Adverse Events. 
Eligible subjects will be randomized to one of 3 treatment arms (3 x 106 PDA-002 cells, 30 x 106 
PDA-002 cells, or placebo) via Interactive Voice Response System (IVRS) across sites in a 
double-blind fashion. 

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8.3. 
Method of Treatment Assignment 
Eligible subjects will be randomized to one of 3 treatment arms (3 x 106 PDA-002 cells, 30 x 106 
PDA-002 cells, or placebo) via Interactive Voice Response System (IVRS) across sites in a 
double-blind fashion. 
The unblinded pharmacist/designee at the study site will prepare the appropriate IP and deliver it 
to the personnel performing the injections.  All other site staff, including the principal 
investigator and research coordinator and sponsor will remain blinded to study treatment 
assignment. 
Pharmacists should consult the pharmacy manual for detailed instructions on the 
preparation and handling of PDA-002 for this study. 
8.4. 
Packaging and Labeling 
Each vial of IP supplied by the sponsor will bear Celgene Cellular Therapeutics’ name and 
address, study product name and descriptor, and traceable lot number.  Additional product 
information including the date of manufacture, the volume of product contained within the vial, 
and cell concentration (for active cells) will also be noted.  Finally, the label will contain the 
standard caution statement for investigational products. 
The syringe rack label, affixed subsequently to thawing/dilution and prior to administration, will 
provide expiry, volume, and handling instructions. 
The label(s) for IP will include sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 
number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable.  Additional information may be included on the label as applicable per local 
regulations. 
8.5. 
Investigational Product Accountability and Disposal 
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus Celgene 
(or designee). 
The investigator(s) or designee is responsible for taking an inventory and performing a visual 
inspection of each shipment of items received and for completing the “Human Placenta-Derived 
Cells (PDA-002) Product Receipt Record” enclosed within the envelope provided with the 
shipment.  The investigator(s) or designee will verify the accuracy of the information on the 
form, sign and date it, retain a copy in the study file, and return a copy to the sponsor. 
At the study site, all investigational IP will be stored in a locked, safe area to prevent 
unauthorized access.  The IP should remain in the cryogenic shipper provided by Celgene until 
time of use. 
Accurate recording of all IP administration (including dispensing and dosing) will be made in the 
appropriate section of the subject’s eCRF and in the source documents. 

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The investigator(s) or designee(s) is responsible for accounting for all IP that is issued to the 
investigative site during the course of the study. 
If any IP is lost or damaged, its disposition should be documented in the source documents.  The 
sponsor will provide instructions to the investigator(s) for the return or destruction of unused IP 
and IP supplies at the end of the study. 
PDA-002 is regulated by the US FDA as a human cellular product.  The FDA (21 Code of 
Federal Regulations [CFR] 1271.290) requires that a record-keeping system be used to track 
human cellular and tissue-based products from the donor to the consignee and vice versa, or any 
other final disposition (for example, shipment was lost or the integrity of the unit was 
compromised).  In accordance with this regulation, Celgene Cellular Therapeutics (CCT) has 
established a tracking system for PDA-002. 
For each unit of PDA-002 that is administered, it is important to maintain records sufficient to 
permit prompt identification of the recipient.  At no time will the identification of the donor be 
known by the subjects in the clinical study. 
To facilitate an effective tracking process: 
 Affix the PDA-002 tracking labels provided with the units to the recipient’s medical 
records and/or other pertinent records, if any, for each unit of PDA-002 that is 
administered to a subject. 
 Maintain the records described above and any other records necessary to permit 
prompt tracking of each unit of PDA-002 to its recipient or other final disposition. 
 Ensure all such records are legible, accurate, indelible, and secure. 
 Ensure all such records are readily available and allow the sponsor and any 
authorized government officers prompt access to such records to the extent required 
by law. 
 Ensure that the record security systems are adequate to ensure the confidentiality of 
recipients who were administered PDA-002. 
 Retain the records referenced in this document for at least 10 years after the date of 
the administration of PDA-002 to the recipient or, if that date is not known, the date 
the product is received or disposed, whichever is latest. 
 Do not further distribute PDA-002. 
Celgene will instruct the investigator on the return, disposal, and/or destruction of investigational 
product and/or medical device materials if applicable.  
Celgene (or designee) will review with the investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus Celgene 
(or designee). 
8.6. 
Investigational Product Compliance 
Accurate recording of all IP administration (including dispensing and dosing) will be made in the 
appropriate section of the subject’s eCRF and in the source documents. 

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8.7. 
Blinding 
With the exception of individuals noted below, all study site personnel, subjects, and sponsor 
personnel and their designees involved with the study, including the sponsor medical monitor 
will remain blinded to treatment assignment until the last subject has completed Month 6 and all 
relevant study data have been processed and integrated into the clinical database and the data 
base is locked. At that time the sponsor and their designees will be unblinded.  Study site 
personnel and subjects will remain blinded during the course of the study.  The personnel in the 
Clinical Supply Management Group responsible for shipping IP and Global Drug Safety 
personnel will be unblinded.  A scientist outside of the study team will be unblinded to assess the 
data on biomarkers. The following personnel external to the sponsor will also be unblinded to 
treatment assignment: the pharmacist, or designee responsible for mixing/ thawing IP, at each 
study site and the IVRS group.  Members of the external DMC will have access to unblinded 
data as specified in Section 6.5.1.   

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9. 
CONCOMITANT MEDICATIONS AND PROCEDURES 
9.1. 
Permitted Concomitant Medications and Procedures 
Concomitant medications and procedures for treatment of DPN are allowed; however, subjects 
should maintain stable doses and stable dose regimens of neuropathy medications (such as 
anticonvulsants like pregabalin, gabapentin, and antidepressant medications such as duloxetine) 
for at least 2 months prior to the initial dose of IP.   
An effort should be made to maintain the subject’s standard medical care through the Treatment 
Period (through Visit 9) unless changes are necessary to ensure the best care for the subject. 
9.2. 
Prohibited Concomitant Medications and Procedures 
It is recommended that subjects continue to maintain stable doses /dose regimens of DPN 
therapies through the Treatment Period (Study Visit 9) whenever possible. 
9.3. 
Required Concomitant Medications and Procedures 
Subjects should receive standard of care prior to and throughout the study.  

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10. 
STATISTICAL ANALYSES 
10.1. 
Overview 
The primary objective of the study is to assess efficacy of PDA-002 in subjects with DPN as 
measured by the change in epidermal nerve histology at 6 months following IM administration of 
2 different doses of PDA-002 or placebo.  Assessment of epidermal nerve histology will be 
quantified using an immunohistochemical technique to determine ENFD. 
The secondary objective of the study is to assess the safety and tolerability of IM administration 
of 2 different doses of PDA-002 or placebo in subjects with DPN.  Safety will be assessed by the 
type, frequency, severity, and potential relationship of adverse events to treatment with IP. 
A detailed Statistical Analysis Plan (SAP) will be provided in a separate document.  Exploratory 
biomarker analysis and other experimental evaluations will be outlined in separate documents 
and will not be included as part of the Clinical Study Report.   
10.2. 
Study Population Definitions 
The following analysis populations are planned for this study: 
Screening Population (Screen):  The Screening Population includes all subjects who provide 
informed consent and screen for eligibility during the Screening Period (Day -28 to Day -1). 
Safety Population (Safety):  The Safety Population includes all subjects who receive any 
amount of IP. 
Modified Intent To Treat (mITT): The mITT population includes all subjects who receive any 
amount of IP and subsequently provide at least one efficacy assessment. 
Other study populations or subgroup populations may be identified during the course of this 
study.  Any additional study populations or subgroups will be clearly identified either in the SAP 
or, if after database lock, then as post-hoc study populations in the clinical study report. 
10.3. 
Sample Size and Power Considerations 
The sample size of 24 subjects total, 8 per treatment arm, was selected in order to provide 
preliminary safety and efficacy information in a randomized, double-blind fashion.  The study is 
designed to provide an estimation of the treatment effect of active therapy and placebo to plan a 
sample size for the next study. 
Based upon a previous study evaluating the therapeutic effect of a combination of 
L-methylfolate, methylcobalamine, and pyridoxal 5 phosphate in subjects with DPN 
(Jacobs, 2011), the mean ENFD was 1.56 fibers/mm at baseline and 3.07 fibers/mm after 6 
months of treatment with a standard deviation of 1.5 fibers/mm for the mean increase.  Assuming 
the same treatment effect is observed from baseline, the sample size of 16 subjects actively on 
therapy resulting from combining the 2 active arms has a 96% power to detect a similar mean 
change at 6 months from baseline, with a two-sided test and a Type I error rate set at 0.05.  
Assuming the subjects treated with placebo would not have a change from baseline, the study has 

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60% power to detect similar differences between placebo and active therapy with PDA-002, with 
a two-sided test and a Type I error rate set at 0.05.   
10.4. 
Background and Demographic Characteristics 
Baseline and demographic characteristic will be summarized by treatment arm.  Subjects’ age, 
height, weight, and baseline characteristics will be summarized using descriptive statistics, while 
gender, race and other categorical variables will be provided using frequency tabulations.  
Medical history data will be summarized using frequency tabulations by system organ class and 
preferred term. 
10.5. 
Subject Disposition 
Subject disposition (analysis population allocation, entered, discontinued, along with primary 
reason for discontinuation) will be summarized using frequency and percentage for both 
treatment and follow-up phases.  A summary of subjects enrolled by site will be provided. 
Protocol deviations will be summarized using frequency tabulations. 
10.6. 
Efficacy Analysis 
The planned analyses will be fully described in a comprehensive SAP.  
The primary efficacy analysis will be an evaluation of change from baseline in ENFD at 6 months 
following treatment with either dose of PDA-002 or placebo. Results will be used to assess the proof 
of concept for further study of PDA-002 in subjects with DPN.  The analyses will also take into 
account the possible inter-subject variability of measurements evaluated in both the treated leg 
(with active or placebo) and the other leg that received placebo. 
Changes in the various exploratory efficacy endpoints including within subject differences 
between left and right leg measurements will be evaluated using descriptive statistics.  
In general, exploratory endpoints that are categorical will be examined using descriptive 
summaries such as counts and percentages, whereas exploratory endpoints that are continuous 
will be examined using means, standard deviations and medians. The results of the exploratory 
analyses will allow for better definition of the clinical efficacy endpoints. 
10.7. 
Safety Analysis 
The safety analyses will be conducted using the Safety Population (all subjects who receive any 
amount of IP).  Adverse events, vital sign measurements, physical examination findings, clinical 
laboratory test results, injection site assessments, retinal assessment results, ECG interpretations, 
and concomitant medications and procedures will be tabulated and summarized as appropriate. 
Adverse events observed will be classified using the Medical Dictionary for Regulatory 
Activities (MedDRA) classification system.  If clinically significant, any or all laboratory 
evaluations should be reported as AEs and repeated more frequently, if clinically indicated.  The 
severity of the toxicities will be graded according to the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 whenever possible. 
The frequency of AEs will be tabulated by MedDRA system organ class and preferred term.  In 
the by-subject analysis, a subject having the same event more than once will be counted only 

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once.  Adverse events will be summarized by NCI CTCAE grade.  Adverse events leading to 
discontinuation from treatment, events classified as NCI CTCAE Grade 3 or higher, study-drug-
related events, and SAEs will be tabulated and listed separately.  By-subject listings of all AEs, 
SAEs, discontinuations due to AEs, and deaths will be provided. 
Clinical laboratory data will be summarized.  Laboratory data will be graded according to NCI 
CTCAE Version 4.03 criteria wherever possible.  The frequencies of the worst severity grade 
observed during treatment will be displayed in cross-tabulations by screening status. 
Vital signs, ECG, and retinal examination data will be summarized by cross-tabulations 
presenting normal and abnormal values. 
Graphical displays will be provided where useful in the interpretation of results. 
10.8. 
Interim Analysis 
An interim analysis will be conducted when the last subject completed Visit 9 (Month 6). 
 

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11. 
ADVERSE EVENTS 
11.1. 
Monitoring, Recording and Reporting of Adverse Events 
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen 
in a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 11.3), regardless of etiology.  Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE.  A diagnosis or syndrome should be recorded on 
the AE page of the eCRF rather than the individual signs or symptoms of the diagnosis or 
syndrome.  
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE.  Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF.  See Section 8.2.2 for the definition of overdose.  Any sequela of 
an accidental or intentional overdose of an investigational product should be reported as an AE 
on the AE eCRF.  In previous studies doses that were one half log greater than the highest dose 
in this study were not associated with any drug related adverse events. If the sequela of an 
overdose is an SAE, then the sequela must be reported on an SAE report form and on the AE 
eCRF.  The overdose resulting in the SAE should be identified as the cause of the event on the 
SAE report form and eCRF but should not be reported as an SAE itself.  
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary.  There is no known specific antidote for PDA-002 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician. 
All subjects will be monitored for AEs during the study.  Assessments may include monitoring 
of any or all of the following parameters:  the subject’s clinical symptoms, laboratory, 
pathological, radiological or surgical findings, physical examination findings, or findings from 
other tests and/or procedures. 
All AEs and SAEs will be recorded by the Investigator from the time the subject signs informed 
consent until the last study visit and those SAEs made known to the Investigator at any time 
thereafter that are suspected of being related to IP.  AEs and serious adverse events (SAEs) will 
be recorded on the AE page of the eCRF and in the subject’s source documents.  All SAEs must 
be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event 
by facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form. 
11.2. 
Evaluation of Adverse Events 
A qualified Investigator will evaluate all adverse events as to:  

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11.2.1. 
Seriousness  
A serious adverse event (SAE) is any AE occurring at any dose that: 
 Results in death 
 Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE) 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay) 
 Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions) 
 Is a congenital anomaly/birth defect 
 Constitutes an important medical event 
Important medical events are defined as those occurrences that may not be immediately life 
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious.  
Any allergic reaction ≥ Grade 3 and associated with the IP is to be reported as an SAE.  
Events not considered to be SAEs are hospitalizations for: 
 A standard procedure for protocol therapy administration.  However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE.  
 Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition. 
 A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling).  However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE. 
 Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE. 
 A procedure that is planned (ie, planned prior to starting of treatment on study); must 
be documented in the source document and the eCRF.  Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE. 
 Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above. 
If an AE is considered serious, both the AE page/screen of the eCRF and the SAE Report Form 
must be completed. 
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to IP, action taken regarding IP, and outcome. 

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11.2.2. 
Severity / Intensity 
For both AEs and SAEs, the Investigator must assess the severity / intensity of the event.  
The severity / intensity of AEs will be graded based upon the subject’s symptoms according to 
the current active minor version of the Common Terminology Criteria for Adverse Events 
(CTCAE, Version 4.03); 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40 
AEs that are not defined in the CTCAE should be evaluated for severity / intensity according to 
the following scale: 
Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required 
Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be needed; no 
or minimal medical intervention/therapy required 
Grade 3 = Severe – marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalization is possible 
Grade 4 = Life threatening – extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalization or hospice care probable 
Grade 5 = Death - the event results in death 
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is 
based on subject/event outcome or action criteria associated with events that pose a threat to a 
subject’s life or functioning.   
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is 
based on subject/event outcome or action criteria associated with events that pose a threat to a 
subject’s life or functioning.   
Seriousness, not severity, serves as a guide for defining regulatory obligations. 
11.2.3. 
Causality 
The Investigator must determine the relationship between the administration of IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below: 
Not suspected: 
Means a causal relationship of the adverse event to IP 
administration is unlikely or remote, or other medications, 
therapeutic interventions, or underlying conditions provide a 
sufficient explanation for the observed event. 
Suspected: 
Means there is a reasonable possibility that the administration 
of IP caused the adverse event.  “Reasonable possibility” means 
there is evidence to suggest a causal relationship between the IP 
and the adverse event. 

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Causality should be assessed and provided for every AE/SAE based on currently available 
information.  Causality is to be reassessed and provided as additional information becomes 
available. 
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP 
that has not been manufactured or provided by Celgene, please provide the name of the 
manufacturer when reporting the event. 
11.2.4. 
Duration 
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event. 
11.2.5. 
Action Taken 
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable 
(eg, discontinuation, interruption, or reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event.  
11.2.6. 
Outcome 
The investigator will report the outcome of the event of both AEs and SAEs. All SAEs that have 
not resolved upon discontinuation of the subject’s participation in the study must be followed 
until recovered, recovered with sequelae, not recovered or death (due to the SAE).  
11.3. 
Abnormal Laboratory Values 
An abnormal laboratory value is considered to be an AE if the abnormality: 
 results in discontinuation from the study; 
 requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or 
 is judged to be of significant clinical importance, eg, one that indicates a new disease 
process and/or organ toxicity, or is an exacerbation or worsening of an existing 
condition. 
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF.  If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets). 
11.4. 
Pregnancy 
All pregnancies or suspected pregnancies occurring in either a female subject or partner of a 
male subject are immediately reportable events 

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11.4.1. 
Females of Childbearing Potential 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or 
disease state) of a female subject occurring while the subject is on IP, or during the course of the 
study, are considered immediately reportable events.  IP is to be discontinued immediately.  The 
pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Celgene Drug 
Safety immediately by facsimile, or other appropriate method, using the Pregnancy Initial Report 
Form, or approved equivalent form. 
The female subject should be referred to an obstetrician-gynecologist, preferably one 
experienced in reproductive toxicity for further evaluation and counseling. 
The Investigator will follow the female subject until completion of the pregnancy, and must 
notify Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form. 
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator 
should report the abnormal outcome as an AE.  If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form. 
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs.  In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
facsimile, or other appropriate method, within 24 hours of the Investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form. 
11.4.2. 
Male Subjects 
If a female partner of a male subject taking investigational product becomes pregnant, the male 
subject taking IP should notify the Investigator, and the pregnant female partner should be 
advised to call their healthcare provider immediately.  
11.5. 
Reporting of Serious Adverse Events 
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the eCRF.  All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form.  This 
instruction pertains to initial SAE reports as well as any follow-up reports. 
The Investigator is required to ensure that the data on these forms is accurate and consistent.  
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent until the last study visit) and any SAE made 
known to the Investigator at anytime thereafter that are suspected of being related to IP.  SAEs 
occurring prior to treatment (after signing the ICF) will be captured. 
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents.  If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 

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Safety as soon as these become available.  Any follow-up data should be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety. 
Where required by local legislation, the Investigator is responsible for informing the IRB/Ethics 
Committee (EC) of the SAE and providing them with all relevant initial and follow-up 
information about the event. The Investigator must keep copies of all SAE information on file 
including correspondence with Celgene and the IRB/EC. 
11.5.1. 
Safety Queries 
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail.  The response time is expected to be no more than five (5) business 
days.  Urgent queries (eg, missing causality assessment) may be handled by phone. 
11.6. 
Expedited Reporting of Adverse Events 
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to PDA-002 based on the Investigator Brochure. 
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32. 
Celgene or its authorized representative shall notify the Investigator of the following 
information.  
 Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR); 
 Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects. 
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC.  (See Section 15.3 for record retention 
information). 
Celgene Drug Safety Contact Information: 
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines. 
 

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12. 
DISCONTINUATIONS 
12.1. 
Treatment Discontinuation 
12.1.1. 
Events Leading to Suspension of Enrollment Pending DMC Evaluation 
The following events in any subject will trigger a suspension of additional enrollment pending an 
evaluation by the Data monitoring Committee (DMC) of the event at an ad hoc meeting. Should 
such an event occur, the DMC will review the available data from the subject’s history and the 
event itself as well as available data on all other previously treated subjects.  The committee will 
recommend if it is appropriate to resume enrollment without study modifications, to resume 
enrollment with study modifications or to permanently discontinue further enrollment into the 
study. Operational details are specified in the DMC Charter. 
 Identification of 1 or more subjects within a dosing treatment arm with ≥ Grade 3 
allergic reaction that is suspected to be related to the IP.  
 Identification of 1 or more subjects experiencing a suspected unexpected, treatment-
related SAE (SUSARs) within 14 days following the initial dose of the IP suspected 
unexpected serious adverse reactions.  
 Identification of 1 or more subjects with a new malignancy.  
12.1.2. 
Mandatory Treatment Discontinuations 
Should subjects experience any of the following events, they may not receive additional doses of 
PDA-002. They should stay on study however, and all scheduled evaluations are to be 
performed. 
 A Grade 3 or higher allergic reaction within 24 hours of PDA-002 administration. 
 An episode of symptomatic arterial vasospasm within 24 hours of PDA-002 
administration.  Examples include acute coronary ischemia and retinal artery spasm. 
 An episode of new venous thrombosis within 3 days of PDA-002 administration. 
12.1.3. 
Additional Treatment Discontinuations 
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product and/or from the study: 
 Adverse event(s) 
 Withdrawal by subject 
 Death 
 Lost to follow-up 
 Protocol violation 
 Pregnancy 

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 Recovery 
 Non-compliance with IP 
 Study terminated by sponsor 
 Physician decision 
 Screen failure 
 Technical problems 
 Disease relapse 
 Failure to meet randomization criteria 
 Site terminated by sponsor 
 Completed 
 Other (to be specified in the eCRF) 
The reason for discontinuation of treatment should be recorded in the eCRF and in the source 
documents. 
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  However, prior to discontinuing 
a subject, the Investigator may contact the Medical Monitor and forward appropriate supporting 
documents for review and discussion.  
Subjects who discontinue will have laboratory assessments performed as specified in the Early 
Termination Column in the Table of Events (Table 1).  
12.2. 
Study Discontinuation 
The following events are considered sufficient reasons for discontinuing a subject from the 
study: 
 Screen failure 
 Adverse event(s) 
 Withdrawal by subject 
 Death 
 Lost to follow-up 
 Other (to be specified in the eCRF)  
The reason for study discontinuation should be recorded in the eCRF and in the source 
documents. 

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13. 
EMERGENCY PROCEDURES 
13.1. 
Emergency Contact 
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page). 
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page).This global Emergency 
Call Center is available 24 hours a day and 7 days a week. The representatives are responsible 
for obtaining your call-back information and contacting the on call Celgene/Contract Research 
organization (CRO) Medical Monitor, who will then contact you promptly. 
Note: The back-up 24 hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.  
13.2. 
Emergency Identification of Investigational Products 
The blind must not be broken during the course of the study unless in the opinion of the 
investigator, it is absolutely necessary to safely treat the subject.  If it is medically imperative to 
know what IP the subject is receiving, IP should be temporarily discontinued if, in the opinion of 
the Investigator, continuing IP can negatively affect the outcome of the subject’s treatment.  The 
Investigator or authorized person should open the randomization envelope/peel apart the 2-part 
label; use an emergency unblinding personal identification number (PIN) and call IVRS for 
unblinded dose information, etc. However, every effort should be made to contact the Clinical 
Research Physician/Medical Monitor prior to breaking the blind. Contact or attempted contact 
with the Clinical Research Physician/Medical Monitor as well as the reason for breaking the 
blind must be documented in the source documents. 
The decision to break the blind in emergency situations remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  However, the Investigator may 
contact the Medical Monitor prior to breaking the blind to discuss unblinding, mainly in the 
interest of the subject.  
The investigator should ensure that the code is broken only in accordance with the protocol.  The 
investigator should promptly notify the Medical Monitor of the emergency unblinding and the 
reason for breaking the blind, which should be clearly documented by the Investigator in the 
subject’s source documentation. 
Emergency unblinding should only be performed by the investigator through the Interactive 
Response Technology (IRT) by using an emergency unblinding personal identification number 
(PIN), and the Investigator should call IRT for unblinded dose information. 

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14. 
REGULATORY CONSIDERATIONS 
14.1. 
Good Clinical Practice 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International 
Conference on Harmonization (ICH) Guideline E6 and in accordance with the general ethical 
principles outlined in the Declaration of Helsinki. The study will receive approval from an 
IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities. 
14.2. 
Investigator Responsibilities 
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff. 
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties. 
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF) and are screened for entry into the study.  Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents. 
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of CRFs and queries. 
The information contained in the protocol and amendments (with the exception of the 
information provided by Celgene on public registry websites) is considered Celgene confidential 
information.  Only information that is previously disclosed by Celgene on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement.  Celgene protocol, amendment and IB information is not to be made publicly 
available (for example on the Investigator’s or their institution’s website) without express written 
approval from Celgene.  Information proposed for posting on the Investigator’s or his/her 
institution’s website must be submitted to Celgene for review and approval, providing at least 5 
business days for review. 
At the time results of this study are made available to the public; Celgene will provide 
Investigators with a summary of the results that is written for the lay person.  The investigator is 
responsible for sharing these results with subjects and/or their caregiver as agreed by the subject. 

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14.3. 
Subject Information and Informed Consent 
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures. 
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original informed consent document signed and dated by the study 
subject and by the person consenting the study subject prior to the study subject’s entry into the 
study, must be maintained in the Investigator’s study files and a copy given to the study subject.  
In addition, if a protocol is amended and it impacts on the content of the informed consent, the 
informed consent document must be revised.  Study subjects participating in the study when the 
amended protocol is implemented must be re-consented with the revised version of the informed 
consent document.  The revised informed consent document signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject. 
14.4. 
Confidentiality 
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws. 
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed informed consent document, it is the responsibility of the Investigator to obtain 
such permission in writing from the appropriate individual. 
14.5. 
Protocol Amendments 
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes. 
14.6. 
Institutional Review Board/Independent Ethics Committee Review 
and Approval 
Before the start of the study, the study protocol, informed consent document, and any other 
appropriate documents will be submitted to the IRB/EC with a cover letter or a form listing the 
documents submitted, their dates of issue, and the site (or region or area of jurisdiction, as 
applicable) for which approval is sought. If applicable, the documents will also be submitted to 
the authorities in accordance with local legal requirements. 

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IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met. 
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the informed consent document 
should also be revised. 
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities. 
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use. 
14.7. 
Ongoing Information for Institutional Review Board / Ethics 
Committee 
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC: 
 Information on serious or unexpected adverse events as soon as possible  
 Periodic reports on the progress of the study 
 Deviations from the protocol or anything that may involve added risk to subjects 
14.8. 
Termination of the Study 
Celgene reserves the right to terminate this study at any time for reasonable medical or 
administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).  
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as: 
 Unsatisfactory enrollment; 
 GCP noncompliance; 
 Inaccurate or incomplete data collection; 

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 Falsification of records; 
 Failure to adhere to the study protocol. 
 

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15. 
DATA HANDLING AND RECORDKEEPING  
15.1. 
Data/Documents 
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained.  Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiche; x-ray film and reports; and records kept at the pharmacy, and 
the laboratories, as well as copies of eCRFs or CD-ROM. 
15.2. 
Data Management 
Data will be collected via eCRF and entered into the clinical database per Celgene SOPs. This 
data will be electronically verified through use of programmed edit checks specified by the 
clinical team.  Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary.  Resolutions to these issues will be reflected in the 
database.  An audit trail within the system will track all changes made to the data. 
15.3. 
Record Retention 
Essential documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IP. The investigator must retain these 
documents for the time period described above or according to local laws or requirements, 
whichever is longer.  Essential documents include, but are not limited to, the following: 
 Signed informed consent documents for all subjects 
 Subject identification code list, screening log (if applicable), and enrollment log 
 Record of all communications between the Investigator and the IRB/EC 
 Composition of the IRB/EC 
 Record of all communications between the Investigator, Celgene, and their authorized 
representative(s) 
 List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures 
 Copies of eCRFs (if paper) and of documentation of corrections for all subjects 
 IP accountability records 
 Record of any body fluids or tissue samples retained 
 All other source documents (subject records, hospital records, laboratory records, etc)  

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 All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial) 
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented.  
All study documents should be made available if required by relevant health authorities. 
Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents. 

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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and SOPs  
16.1. 
Study Monitoring and Source Data Verification 
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study.  All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an investigator meeting.  Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, eCRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator.  Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone.  During monitoring visits, the facilities, 
investigational product storage area, eCRFs, subject’s source documents, and all other study 
documentation will be inspected/reviewed by the Celgene representative in accordance with the 
Study Monitoring Plan. 
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made into the eCRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified.  Additional 
monitoring activities may be outlined in a study-specific monitoring plan. 
16.2. 
Audits and Inspections 
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene.  Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations. 
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, eCRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/IECs, regulatory authorities (eg, FDA, European Medicines 
Agency (EMA), Health Canada) and company authorized representatives.  The Investigator 
should make every effort to be available for the audits and/or inspections.  If the Investigator is 
contacted by any regulatory authority regarding an inspection, he/she should contact Celgene 
immediately. 

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17. 
PUBLICATIONS 
As described in Section 14.2, all protocol- and amendment-related information, with the 
exception of the information provided by Celgene on public registry websites, is considered 
Celgene confidential information and is not to be used in any publications.  Celgene protocol-
related information proposed for use in a publication must be submitted to Celgene for review 
and approval, and should not be used in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement.   
Celgene will ensure that Celgene-sponsored studies are considered for publication in the 
scientific literature in a peer-reviewed journal, irrespective of the results.  At a minimum, this 
applies to results from all Phase 3 clinical studies, and any other study results of significant 
medical importance.  This also includes results relating to investigational medicines whose 
development programs have been discontinued. 
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes.  Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations.   
Eligibility for external authorship, as well as selection of first authorship, will be based on 
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation on the study steering 
committee (when applicable) and contribution to abstract, presentation and/or publication 
development.   
 

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18. 
REFERENCES 
Aggarwal S, Pittenger MF.  Human mesenchymal stem cells modulate allogeneic immune cell 
responses.  Blood 2005;105(4):1815-22. 
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 
2014;37(Suppl. 1):S81–S90. 
Campeau L. Grading of angina pectoris (Letter to the Editor). Circulation. 1976; 54: 522-523.  
Centers for Disease Control and Prevention, National diabetes fact sheet, 2011.  Fast facts on 
diabetes.  Atlanta, GA: US Department of Health and Human Services, 2011.   
Heart Failure Society of America.  http://www.hfsa.org/hfsa-wp/wp/stages-of-heart-failure 
Accessed 25 February 2015. 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
International Clinical Diabetic Retinopathy Disease Severity Scale. 
one.aao.org/asset.axd?id=321d1c98-7ded-45a6-b663-8edbd2ef55dd International clinical 
diabetic retinopathy disease severity scale. Accessed 07 May 2014. 
Jacobs AM, Cheng D.  Management of diabetic small-fiber neuropathy with combination L-
methylfolate, methylcobalamin, and pyridoxal 5’-phosphate.  Reviews in Neurological Diseases 
2011;8(1/2):39-46. 
Kles KA, Vinik AI.  Pathophysiology and treatment of diabetic peripheral neuropathy: the case 
for diabetic neurovascular function as an essential component. Curr Diabetes Rev 2006; 2:131-
145. 
Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al.  Using standardized 
serum creatinine values in the modification of diet in renal disease study equation for estimating 
glomerular filtration rate.  Ann Intern Med 2006;145(4):247-54.  
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
v 4.03 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40. 
Nauta AJ, Fibbe WE.  Immunomodulatory properties of mesenchymal stromal cells.  Blood 
2007;110(10):3499-506. 
The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for the 
Diagnosis of Diseases of the Heart and Great Vessels. 9th ed; 1994: 253-256.  
The Criteria Committee of the New York Heart Association.  NYHA classification – The stages 
of heart failure.  Heart Failure Society of America.  
http://www.abouthf.org/questions_stages.htm.  Accessed September 28, 2012. 
World Health Organization 
http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_n
ew.pdf. Accessed 23 Feb 2015. 

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19. 
APPENDICES 
Appendix A: 
American Diabetes Association (ADA) and World Health 
Organization (WHO) Diabetes Mellitus Type 2 Definition 
 
Diagnostic Criteria by the American Diabetes Association (ADA) (ADA, 2014) include the 
following: 
1. A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher,  
or 
2. A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral 
glucose tolerance test (OGTT),  
or 
3. A random plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher in a subject with 
classic symptoms of hyperglycemia or hyperglycemic crisis  
or 
4. HbA1C of 6.5%. The test should be performed in a laboratory using a method that is 
National Glycohemoglobin Standardization Program (NGSP) certified and standardized 
to the Diabetes Control and Complications Trial (DCCT) assay. 
Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher should be a primary diagnostic 
criterion or an optional criterion remains a point of controversy.  
WHO Definition 
Currently HbA1c is not considered a suitable diagnostic test for diabetes or intermediate 
hyperglycemia. 
The following summarizes the 2006 WHO recommendations for the diagnostic criteria for 
diabetes and intermediate hyperglycemia (WHO 2006). 
Diabetes 
Fasting plasma glucose  
1. 2–h plasma glucose*≥7.0 mmol/l (126 mg/dl) 
or 
2. ≥11.1mmol/l (200 mg/dl) 
Impaired Glucose Tolerance (IGT) 
Fasting plasma glucose 2–h plasma glucosea 
1. <7.0 mmol/l (126mg/dl) and ≥7.8 and <11.1 mmol/l (140 mg/dl and 200 mg/dl) 

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Impaired Fasting Glucose (IFG) 
Fasting plasma glucose 2–h plasma glucosea,b  
1. 6.1 to 6.9 mmol/l (11 0mg/dl to 125 mg/dl)  
and 
2. (if measured) <7.8 mmol/l (140 mg/dl) 
a Venous plasma glucose 2–h after ingestion of 75 g oral glucose load. 
b If 2–h plasma glucose is not measured, status is uncertain as diabetes or IGT cannot be excluded. 
 
 

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Appendix B: 
International Clinical Diabetic Retinopathy Disease 
Severity Scale  
 
 
 
International Clinical Diabetic Retinopathy Disease Severity Scale 
Proposed Disease Severity Level 
Findings Observable upon Dilated 
Ophthalmoscopy 
No apparent retinopathy 
No abnormalities 
Mild nonproliferative diabetic retinopathy 
Microaneurysms only 
Moderate nonproliferative diabetic 
retinopathy 
More than just microaneurysms but less than 
severe NPDR 
Severe nonproliferative diabetic retinopathy Any of the following: 
 More than 20 intraretinal hemorrhages in 
each of four quadrants 
 Definite venous beading in two or more 
quadrants 
 Prominent IRMA in one or more quadrants 
And no signs of proliferative retinopathy 
Proliferative diabetic retinopathy 
One or both of the following: 
 Neovascularization 
 Vitreous/preretinal hemorrhage 
IRMA = intraretinal microvascular abnormalities; NPDR = nonproliferative diabetic retinopathy. 
 
 
 

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Appendix C: 
New York Heart Association (NYHA) Classification 
 
Class 
Patient Symptoms 
Class I (Mild) 
No limitation of physical activity.  Ordinary physical activity does not cause 
undue fatigue, palpitation, or dyspnea (shortness of breath). 
Class II (Mild) 
Slight limitation of physical activity.  Comfortable at rest, but ordinary physical 
activity results in fatigue, palpitation, or dyspnea. 
Class III (Moderate) 
Marked limitation of physical activity.  Comfortable at rest, but less than 
ordinary activity causes fatigue, palpitation, or dyspnea. 
Class IV (Severe) 
Unable to carry out any physical activity without discomfort.  Symptoms of 
cardiac insufficiency at rest.  If any physical activity is undertaken, discomfort 
is increased. 
Source:  The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for the Diagnosis 
of Diseases of the Heart and Great Vessels. 9th ed. Boston, 1994: 253-6.  Heart Failure Society of America.  
http://www.hfsa.org/hfsa-wp/wp/stages-of-heart-failure. Accessed 25 February 2015. 
 
 
 

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Appendix D: 
Canadian Cardiovascular Society Angina Grading Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Source: Campeau,1976. 
 
 
 

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Appendix E: 
Thawing Protocol 
Instructions for Thawing and Preparing PDA-002 
Thawing Protocol and Vial Preparation 
This section must be conducted by an unblinded pharmacist or by delegated, trained study 
personnel. 
1. Obtain confirmation of enrollment from delegated personnel responsible for registering 
subject’s demographic information in the Interactive Web Response System (IWRS).  
You will need this information to cross-check the subject ID number and the information 
on the vial.   
2. Wearing appropriate personal protective equipment, obtain frozen vial from the shipping 
container.  
3. Record start time of the thaw procedure. 
If using a water bath, follow steps in bullet 4.  
4. Water Bath Instructions 
a.  Rapidly transfer the frozen vial into a water bath float.  
b. Transfer the float and vial into a 37°C water bath such that the vial body is 
immersed in the water and the lid of the vial is supported by the float. 
c. Remove the vial from the water bath after 9 minutes.  Investigational product (IP) 
should be predominantly thawed, but may contain a small residual ice crystal.  
d. Remove the thawed vial from float, and dry off any excess moisture from the 
outside of the vial.  
If Celgene Cellular Therapeutics (CCT) supplies alternate equipment for thawing, a separate 
manual for the thawing process will be provided. 
5. Ensure the vial is well mixed by gently inverting the vial 3 times. 
6. Confirm the contents of the vial by verifying that the vial label matches the information 
on the appropriate forms.  
7. Prepare the vial by removing the lid cap from the vial. Wipe the vial septum with 70% 
isopropyl alcohol, allow the alcohol to dry, and insert a self-venting Mini-Spike through 
the septum. 
8. Cover the vial label with the provided product expiration sticker.  
9. Blind the vial using the provided blinding bag and secure in place. Place a second product 
expiration label on the blinded vial. 
10. Blind and label the provided 3 mL syringes using the provided syringe blinding labels. 
11. Record the date, time of thaw, expiration time, and subject identifier on the appropriate 
forms.  The product expiration time is 4 hours from the time the vial was thawed.  
 

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Syringe Filling Protocol  
Prepare as per your institutions’ Standard Operating Procedure by a delegated, trained study 
personnel.  Use aseptic technique. 
1. Ensure that the vial is well mixed by gently inverting the vial 3 times. 
2. Remove the cap from the Mini-Spike and attach a blinded/labeled 3 mL syringe to the 
vial. 
3. Orient the vial above the syringe such that the contents can be withdrawn into the 
syringe, and retrieve 1.5 mL of the solution. Ensure that no air bubbles are present in the 
syringe. 
4. Disconnect the syringe from the Mini-Spike and connect it to a 22 gauge needle. If not 
used immediately (within 30 minutes), the IP may be stored in capped syringes oriented 
vertically (needle side down) for up to 1 hour in the syringe rack provided. 
5. Attach the next syringe to the vial then repeat Steps 3 and 4 until all 3 syringes have been 
filled. 
6. Record the time the syringes are filled on the Subject Dispensation Log. The product 
should be administered within 1 hour from the time the syringes are filled. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Suggested Injection Pattern in the Gastrocnemius or Soleus Muscle.  
 
                                     
     
 
The following recommendations are made with the understanding that the investigator or 
designee will use his/her own judgment on how best to administer the treatment. 
 Subjects will be treated with IP administered intramuscularly (IM) on Study Days 1, 
29 and 57.  
 The target region on the limb is below the knee and above the ankle in the 
gastrocnemius or soleus muscle.  
 Injections are to be at least 1 cm apart horizontally and laterally and at a depth of 
approximately 1 to 4 cm.  For subjects near their ideal weight, inject at 2 to 3 cm 
depth.  For obese subjects, inject toward the deeper end of the range; for thin subjects, 
inject toward the shallower end of the range. 
 PDA-002 is not intended for intravenous (IV) administration.  When the injection is 
given, the syringe should be aspirated to avoid inadvertent venous administration.  If 
any blood is aspirated into the syringe, the needle is to be pulled out a little, and the 
syringe reaspirated. If no blood is observed the IP may be injected. 
 Injections are to be administered in a pattern of 3 x 5 injections around the leg and 
injections should not be near a blood vessel.  See diagram above for injection pattern.