Viable Allograft Supplemented Disc Regeneration in the Treatment of Patients With Low Back Pain With or Without Intervertebral Disc Herniation - VAST Trial
Phase: NA
Conditions: Degenerative Disc Disease
Sponsor: VIVEX Biologics, Inc.

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
TG, DB, PW    
NO. 
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Page 1 of 62 
 
1.1 
CONFIDENTIAL 
The information contained herein is confidential and proprietary information of Vivex 
Biologics, Inc. It is intended solely for the use of Vivex Biologics, Inc. and its designated 
clinical investigators or institutional review committees, and others directly involved in 
this clinical investigation who are bound to the confidentiality obligations of a 
Confidentiality Agreement between Vivex Biologics, Inc. and the investigators participating 
in this study.  If you are not the designated recipient, please call us immediately at to 
arrange for the return of this information.  Any review, dissemination, distribution, 
copying, or use of this information by anyone other than the designated recipient(s) is 
strictly prohibited. 
Viable Allograft Supplemented Disc Regeneration in the Treatment of Patients with Low Back 
Pain with or without Intervertebral Disc Herniation – VAST Trial 
           
 
Sponsor:   
Vivex Biologics, Inc. 
3200 Windy Hill Road 
Suite 1650 W 
Atlanta GA 30339 
855.698.4839 
Sponsor Contact:  
Peyton Warley, Clinical Program Manager 
 
 
 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
TG, DB, PW    
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REV 
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Page 2 of 62 
 
Principal Investigator (s):   
Address  Douglas Beall, MD; Interventional Musculoskeletal Radiology, 1800 South Renaissance Blvd, 
Suite 110, Edmond, OK 73013 
Address  William Tally, MD; Athens Orthopedic Clinic, 1765 Old West Broad St. Bldg. 2, Ste. 200, Athens, 
GA 30606 
Address  Randolph (Randy) Bishop, MD; Neurological Institute of Savannah and Center for Spine, 4 
Jackson Boulevard, Savannah, GA 31405 
Address  Christopher Hancock, MD; Desert Medical Imaging. 74785 CA-111 #101, Indian Wells, CA 92210 
Address  Timothy Davis, MD; Orthopaedic Pain Specialists, 2428 Santa Monica Blvd, Suite 208 
Santa Monica, CA 90404 
Address  Gregory L. Wilson, DO; Invictus Healthcare, 9709E E 79th St, Tulsa, OK 74133 
Address  Michael DePalma, MD; Virginia Spine Physicians, 9020 Stony Point Parkway, Suite 140, 
Richmond, VA 23235 
Address  Ben Guiot, MD; Centura Health Research Center, 2525 S. Downing St., Denver, CO 80210 
Address  Kasra Amirdelfan, MD; John Muir Health, 450 N Wiget Ln, Walnut Creek, CA 94598 
Address Richard Guyer, MD; Texas Back Institute, 6020 W. Parker Road, Suite 200 (2nd Floor), 
Plano TX 75093 
Address Corey Hunter, MD; Ainsworth Institute of Pain Management, 115 East 57th St., Suite 1210, New 
York, NY 
Address Razmig Haladjian, MD; Michigan Interventional Pain Center, 19725 Allen Road; Building 1; Suite 
A, Brownstown, MI 48183 
Address Meredith Langhorst, MD; Orthopedic Research Foundation, 8450 Northwest Blvd, Indianapolis, 
IN 46278 
Address Steven Gershon, MD; Gershon Pain Specialists, 1133 First Colonial Road, Virginia Beach, VA 
23454 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
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Page 3 of 62 
 
 
Product: VIA Disc 
 
Trial Number: VAST-001-017 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
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Page 4 of 62 
 
PROTOCOL APPROVAL FORM 
Protocol No: VAST-001-017 
Study Title: 
 
Viable Allograft Supplemented Disc Regeneration in the Treatment of Patients with Low Back 
Pain with or without Intervertebral Disc Herniation – VAST Trial 
 
This study protocol was subjected to critical review. The information it contains is consistent 
with Vivex’s current knowledge of the risks and benefits of the, as well as with the moral, ethical 
and scientific principles governing clinical research as set out in the Declaration of Helsinki, as 
amended in 2000 and clarified in 20041, and the guidelines on Good Clinical Practice.   
The study protocol has been reviewed and approved by the following: 
 
Douglas Beall, MD______________________ 
_____________________ 
Name 
 
 
 
 
 
 
  
 
Date 
Principal Investigator 
 
Timothy Ganey, PhD_________________________ _____________________ 
Name 
 
 
 
 
 
 
  
 
Date 
Protocol Author 
 
Shab Namin, PhD___________________________ _____________________ 
Name 
 
 
Date 
Study Manager 
 
H. Thomas Temple, MD_____________________ 
_____________________ 
Chief Medical Officer 
 
 
Date 
 
 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
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Page 5 of 62 
 
Investigator’s Statement: “I agree to conduct this clinical study in accordance with the design 
and specific provisions of this protocol; modifications to the study are acceptable only with a 
mutually agreed upon protocol amendment. I agree to await IRB approval for the protocol and 
informed consent before initiating the study to obtain consent from potential subjects prior to 
their enrollment into the study, to collect and record data as required by this protocol and case 
report forms, to prepare annual, final and adverse event reports as required by this protocol, and 
to maintain study documentation for the period of time required.” 
 
Principal Investigator Signature                     
Date of Signature 
 
This document contains confidential information belonging to Vivex Biologics, Inc.  Except as 
otherwise agreed to in writing, by accepting or reviewing Protocol VATS-001-017, you agree to 
hold this information in confidence and not to disclose it to others (except where required by 
applicable law) or to use it for unauthorized purposes. In the event of any actual or suspected 
breach of this obligation, Vivex Biologics, Inc. should be promptly notified 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
TG, DB, PW    
NO. 
6 
REV 
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Page 6 of 62 
 
TABLE OF CONTENTS 
1.1 
CONFIDENTIAL 
1 
STUDY CONTACTS 
9 
PROTOCOL SYNOPSIS 
10 
2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
16 
3 
OBJECTIVE 
17 
4 
BACKGROUND 
18 
4.1 
In-vitro studies 
19 
4.2 
Pre-clinical studies 
19 
4.3 
Clinical studies 
20 
5 
RATIONALE 
22 
6 
STUDY DESIGN 
24 
6.1 
Study Population 
25 
6.2 
Patient Identification and Randomization 
25 
6.3 
Blinding 
26 
6.4 
Treatments administered 
26 
6.5 
Identity of investigational product(s) 
26 
6.6 
Selection of the study dose 
26 
6.7 
Prior and concomitant therapy 
27 
6.8 
Treatment compliance 
27 
6.9 
Study Duration 
27 
6.10 
Subject Withdrawal and Replacement 
28 
7 
EFFICACY AND SAFETY MEASUREMENTS 
29 
7.1 
Study Procedure 
29 
7.1.1 
Screening Phase Day -14 to Day 0 or VS1: 
29 
7.1.2 
Active Phase Day 0 or VA1: 
29 
7.1.3 
Active Phase 1 Month (± 30 days), or VA2 
30 
7.1.4 
Conservative Treatment Group 3 Months (±14 days), or VA3 
30 
7.1.5  
Active Phase Month 6 (±30 days), or VA4 
30 

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Clinical Protocol  
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 7.1.6  
Active Phase Month 12 (+ 30 days) or VA5 
31 
7.1.7 
Optional Long-Term Follow Up Month 24 & Month 36 (± 3 Months) or 
VA6 & VA7 
31 
7.2 
Appropriateness of measurements 
31 
7.2.1 
Primary efficacy variable 
32 
7.2.2 
Secondary efficacy variables 
32 
8 
INCLUSION / EXCLUSION CRITERIA 
33 
8.1 
Inclusion Criteria 
33 
8.2 
Exclusion criteria: 
34 
MATERIALS AND METHODS 
35 
8.3 
Test Material 
35 
8.4 
Study Procedure 
35 
8.4.1 
Transplant of supplemental allograft into the affected disc 
35 
8.5 
Assessments 
36 
8.6 
Study Schedule 
38 
9 
STUDY OBJECTIVES AND ENDPOINTS 
39 
9.1 
Objective 
39 
9.2 
Primary Endpoint 
39 
9.3   
Secondary Endpoints 
39 
10 
RISKS 
40 
10.1 
Transplantation Risk Management 
40 
10.2 
Overall Study Risk Management 
40 
11 
BENEFITS 
41 
12 
RISK / BENEFIT ANALYSIS 
42 
13 
DATA ANALYSIS 
43 
13.1 
Data Management 
43 
13.1.1 
Data collection 
43 
13.1.2 
Database management and quality control 
43 
13.1.3 
Interim analysis 
43 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
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Page 8 of 62 
 
13.2 
Statistical Methods and Determination of Sample Size 
43 
13.2.1 
Populations for analysis 
43 
13.2.2 
Statistical and analytical plans 
43 
13.3 
Sample Size Considerations 
44 
14 
ADVERSE EVENTS / SERIOUS ADVERSE EVENTS 
45 
14.1 
Adverse Event 
45 
14.2 
Serious Adverse Event 
46 
14.3 
Serious Unanticipated Adverse Device Effect 
46 
14.4 
Procedures for AE Reporting 
46 
15 
REGULATORY OBLIGATIONS 
48 
15.1 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 
48 
15.2 
Informed Consent Process 
48 
15.3 
Steering Committee 
49 
15.4 
Site Selection and Qualification 
49 
15.5 
Site Initiation 
49 
15.6 
Monitoring 
50 
15.7 
Required Reports 
50 
16 
STUDY REQUIREMENTS 
52 
16.1 
Quality Assurance 
52 
16.2 
Monitoring 
53 
17 
PROCEDURES AND INSTRUCTIONS 
55 
17.1 
Special safety-related procedures 
55 
17.2 
Administrative procedures 
55 
17.3 
Ethics and Good Clinical Practice 
55 
APPENDIX A - STUDY SCHEDULE 
56 
APPENDIX B– Supplemental TRANSPLANTATION /OTHER APPENDICES 
58 
APPENDIX C – Supplemental TRANSPLANTATION 
59 
REFERENCE LIST 
60 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
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Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
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Page 9 of 62 
 
STUDY CONTACTS 
Sponsor: 
 
 
Vivex Biologics, Inc. 
 
 
 
 
3200 Windy Hill Road 
Suite 1650 W 
Atlanta GA 30339 
855.698.4839 
 
Medical Monitor: 
 
H. Thomas Temple, MD 
 
 
 
 
Chief Medical Officer 
Vivex Biologics, Inc. 
 
 
 
 
 
 
 
 
 
Phone: 855-698-4839 
 
 
 
 
 
Clinical Representative: 
Peyton Warley 
 
 
 
 
Clinical Program Manager 
 
 
 
 
Vivex Biologics, Inc. 
 
 
 
 
 
 
 
 
 
Phone: 855-698-4839 
 
Principal Investigator: 
Douglas Beall, MD 
 
1800 South Renaissance Blvd. 
 
Suite 110 
 
Edmond, OK 73013 
 
Phone:  405.601.2325 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
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REV 
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Page 10 of 62 
 
PROTOCOL SYNOPSIS 
Title 
Viable Allograft Supplemented Disc Regeneration in the 
Treatment of Patients with Low Back Pain with or without 
Intervertebral Disc Herniation – VAST Trial 
 
Objective 
To evaluate the safety and efficacy of viable allograft 
transplantation for the treatment of patients with 
symptomatic disc degeneration and tissue loss 
Study Design 
Multi-center, prospective, parallel, triple arm study to assess 
patients who participated in the VAST trial and receiving either 
viable allograft, saline, or allograft after cross-over. These 
patients will be evaluated at baseline, injection, 6 months, and 
12 months. Subjects will then have an option for a 24 months 
and 36 months extension after their index procedures. Patients 
who received saline or active allograft in the VAST study, will 
be allowed to receive viable allograft and followed for an 
additional 12 and 24 months after that election. These subjects 
will need to meet initial inclusion/exclusion criteria again 
before another injection.  
 
Endpoints 
 
Primary: 
• Improvement in Oswestry Disability Index (ODI) at 6 
and 12 months after treatment. 
• Durability of Oswestry Disability Index (ODI) at 24 and 
36 months after initial inclusion compared with 12 
month improvement.  
• Improvement in Visual Analogue Scale of Pain Intensity 
(VASPI) at 6, and 12 months after treatment. 
• Durability of Improvement in Visual Analogue Scale of 
Pain Intensity (VASPI) 24 months and and 36 months 
after initial inclusion compared with 12 month 
improvement. 
 
Secondary 

CONFIDENTIAL 
Clinical Protocol  
DATE 
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Page 11 of 62 
 
• Improvement in ODI, SF-36, and VASPI at 6 and 12 
months after treatment 
• Improvement in ODI, SF-36, and VASPI scores for 
optional 24 month and 36 month follow up subjects 
• X-ray and MRI measurements at 6 and 12 months after 
treatment 
• AE/SAE rates after treatment 
• Hospitalization rate at 12, 24, or 36 months after 
treatment 
• Re-operation rate at 12, 24, or 36 months after 
treatment 
• Resource utilization following treatment and at 6 and 
12 months (and optional 24 & 36 month) follow up 
visits 
 
Study Population 
Patients evaluated for degenerative intervertebral disc disease 
demonstrating Pfirrmann Grade [3-6] by MRI 
Clinical Sites 
Up to twenty (20) sites in the United States 
 
Sample size and 
randomization 
Approximately 220 subjects randomized to viable allograft or 
placebo or control in 3.5:1:1 ratio: 
nactive   = 140 
nplacebo  =     40 
ncontrol =    40 
 
For study extension: The original randomized population will 
be pooled and reconsented for an optional follow up for 24 
and 36 months.  
 
Study Design 
The study is composed of three separate phases. 
There will be the Screening Phase followed by the Active Phase 
equaling 12 months then followed by the optional long term 
follow up at 24 months and 36 months.  Patients need to meet 
entry criteria for all phases.     

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
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REV 
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Page 12 of 62 
 
During the Screening Phase, subjects will be assessed for study 
eligibility, X-ray and MRI within the previous 6 months, SF-36, 
ODI, and VASPI to establish a baseline for participation. If 
meeting eligibility, they will be scheduled for allograft 
treatment, placebo (saline) treatment, or conservative care 
treatment.  
Those who meet the Active Phase entry criteria will be 
randomized at Day 0 to either receive the viable allograft, 
placebo as saline, or be assigned to continue conservative 
treatment.  Specified subjects, as noted below, will return to 
the clinic for a safety assessment 1 month after the transplant, 
and subsequently at 6, and 12 months for safety and efficacy 
assessments. Patients who continue conservative care will be 
evaluated at 3 months, as well as 6 and 12 months. Physicians 
at their discretion can bring subjects back for follow-up to 
assure safety at any time point throughout the duration of the 
study. 
The first 24 patients to be randomized (at least 4 from each 
treatment group) will have an additional study visit 1 month 
after treatment. All data from the 1-month study visit will be 
collected and reviewed by the Steering Committee to confirm 
that enrollment can continue.   
Subjects will have the option to continue with a long-term 
follow up at time points of 24 and 36 months. Questionnaires 
will be completed over the phone with the study coordinator’s 
prompting or during an in-office visit. All randomized subjects 
will also have the option to receive an allograft injection during 
the 24 month office visit after meeting inclusion/exclusion 
criteria.  
Inclusion Criteria 
• Able to provide an English written Informed Consent  
• Age 18 to 60 years inclusive 
• Male or female 
• Body mass index <35 
• Pfirrmann Grade [3-6] 

CONFIDENTIAL 
Clinical Protocol  
DATE 
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• Radiographic confirmation by MRI/X-ray of: 
(1) translational instability defined as ≤5 mm, or 
(2) angular instability defined as ≤5° 
• Back pain (with or without radicular leg pain) measured by: 
(1) ODI of at least 40%, and  
(2) VASPI of at least 40mm 
• Pathologic level between L1 and S1 
• 1 or 2 vertebral level involvement that has been evaluated 
for at least 6 months and treated with conservative care 
• Symptomatic back pain attributable to intervertebral disc 
for a minimum of 6 months 
• No previous surgical treatment at the disc level(s) being 
considered 
• Psychosocially, mentally and physically able to fully comply 
with this protocol, and follow-up schedule 
• Ability to undergo allograft transplantation 
• Life expectancy >2 years 
• No contraindications to MRI 
• No history of malignancy (basal cell carcinoma) or chronic 
infectious disease (e.g. HIV, Hepatitis) 
• Agree to use appropriate contraception; not planning on 
becoming pregnant for 24 months after treatment 
• Patient disc for transplant confirmed by inter-discal pressure 
measurement, or disc-imaging study. 
• No signs or symptoms of infection 
• No chronic use (>7 consecutive days) of anticoagulants (such 
as aspirin) or NSAIDs prior to treatment   
 
 
Exclusion Criteria 
• Seropositive or seronegative spondyloarthropathy  
• Type III Modic changes 
• Prior surgeries of segments between L1 and S1 
• Chemonucleolysis or percutaneous laserectomy of the 
affected disc prior to the study 
• Chronic facet syndrome 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
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Page 14 of 62 
 
• Stenosis of the spinal canal that is moderate to severe or 
more in degree 
• Spondylodiscitis 
• Spondylolisthesis (lysis and degenerative) 
• Severe motor deficit or cauda equina disorder based on 
investigator determination 
• Congenital abnormalities of the spinal nerves 
• Pelvic and inguinal angiopathy 
• Neurogenic inguinal syndrome 
• Syringomyelia 
• Diastenomatomyelia 
• Traumatic neurological disorders 
• Diseases of the kidney (nephritis, pyelonephritis)  
• Other severe diseases of any other major body system as 
judged by the investigator 
• Regular intake of systemic steroids 
• Malignant diseases of any solid organ or any hematologic 
malignancy during the previous 5 years 
• Patients who have participated in a clinical trial within the 
last month prior to inclusion 
• Moderate to severe or greater lumbar stenosis of both 
transplantation endplates and adjacent levels  
 
Treatment Strategy 
Single, or two-level intervertebral disc treatment with viable 
allograft, placebo, or conservative care treatment for 
Pfirrmann grade III - VI disc imaging assessment 
Statistical Analysis 
Primary analysis: 
The primary efficacy analysis will be performed on the 
modified intent-to-treat (MITT) population. The MITT 
population is defined as all subjects who underwent the viable 
allograft treatment or placebo treatment, and at least one 
valid post-transplant assessment of ODI and VASPI.  
The null hypothesis is that there is no difference in ODI at 12 
months following viable allograft implantation between the 
three treatment groups 1.) Allogeneic Cells with supplemental 

CONFIDENTIAL 
Clinical Protocol  
DATE 
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Page 15 of 62 
 
micronized nucleus pulposus, 2.) saline, or 3.) conservative, 
non-surgical, care. 
For all Screening and Active Phase baseline data, descriptive 
statistics will be presented.  A hierarchical test procedure will 
be applied. In the first step the distributions of the pre-post 
difference of the groups will be compared using Wilcoxon 
rank-sum-test. In case of a significant result, a responder 
analysis will be done using Fisher’s exact test. All secondary 
variables will be analyzed in an exploratory way using 
adequate statistical procedures 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
VAST-001-017 
WRITER      
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Page 16 of 62 
 
2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse Event 
CRF 
Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
IRB 
Institutional Review Board 
ITT 
Intention To Treat 
LOCF 
Last Operation Carried Forward 
MEC 
Medical Ethics Committee 
MITT 
Modified Intent-To-Treat 
MRI 
Magnetic Resonance Imaging  
n 
Number 
NaCl 
Sodium chloride 
NP 
Nucleus pulposus 
OPDQ 
Oswestry Low Back Pain Disability Questionnaire 
ODI 
Oswestry Disability Index 
PP 
Per Protocol 
PTT 
Partial thromboplastin time 
SAE 
Serious Adverse Event 
SAS 
Statistical analysis system 
SF-36 
Short Form 36 
SOP 
Standard Operating Procedure 
SUADE 
Serious Unanticipated Adverse Device Event  
UADE 
Unanticipated Adverse Device Event 
V 
Visit 
VASPI 
Visual Analogue Scale of Pain Intensity 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
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Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
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Page 17 of 62 
 
3 
OBJECTIVE 
The objective of this study is to evaluate the safety and efficacy of viable allograft 
transplantation for the treatment of patients with symptomatic disc degeneration and tissue 
loss. 
The primary criterion is the outcome of the Oswestry Low Back Pain Disability Questionnaire 
(OPDQ) modified according to Hudson-Cook and calculated as the Oswestry Disability Index 
(ODI) at 6 and 12 months after transplant, and the Visual Analogue Scale of Pain Intensity 
(VASPI) at 6, and 12 months following allograft supplementation. Secondary parameters of 
efficacy will include SF-36. Structural outcomes will be assessed using X-ray and Magnetic 
Resonance Image (MRI) measurements at 12 months. Safety will be assessed by the incidence 
and severity of adverse events (AEs) and clinically important changes in laboratory tests. All 
subjects (excluding conservative care crossover subjects) will be randomized to include MRI at 
6-month follow-up (MRI or no MRI,  ratio 1:1) in addition to all other assessments. Subjects 
randomized to conservative care will be assessed at 3 months. If at 3 months these subjects 
demonstrate a significant decline in condition, they will be offered the option to receive 
allograft treatment and will be followed for the subsequent 6 and 12 months. The conservative 
care subjects that crossover to the allograft treatment group will all receive an MRI at 6-month 
and 12-month follow-up after allograft treatment.   
A correlation of the clinical results (scores) and the morphological results (X-ray, MRI) will be 
evaluated. All additional efficacy and safety data will be analyzed descriptively. 
The optional long-term follow up will allow for additional objectives to be analyzed. At 24 and 
36 months, subjects will have the opportunity to fill out VASPI, ODI, SF-36, and Resource 
Utilization forms which will be analyzed and compared to the original 12-month data. The 
active allograft and placebo cross over to allograft treatment at 24 months will also be asked to 
fill out the same questionnaires. This data will be compared to the first 12 months of data in the 
placebo group.  

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
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Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
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REV 
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Page 18 of 62 
 
4 
BACKGROUND 
Degenerative changes of the lumbar segments are an inevitable consequence of the aging and 
are often a reason for chronic back pain and neurological complications.  It has been estimated 
that nearly 80% of the population suffer from lower back pain at least once during their 
lifetime2,3 and during recent years degenerative changes of the lumbar segments have become 
an outstanding medical problem in the industrialized nations.4,5  Progress in clinical medicine 
has acknowledged several patho-mechanisms of intradiscal mass change(s) with respect to disc 
herniation as well as degeneration. In general, the main reason for disc herniation is attributed 
to trauma, and the degree of degeneration of the disc and the trauma causing herniation vary 
widely but are correlated. Making the connection important but perhaps more challenging is 
information regarding degenerative changes linked to genetic, metabolic, and mechanical 
imbalance. 6,7,8,9,10 
The development of chronic back pain after lumbar disc herniation in conjunction with 
degenerative changes results in a medical condition often treated surgically.  Besides 
conservative non-surgical methods such as rest, physical therapy, and bracing, often times 
surgical processes such as discectomy, total intervertebral disc prosthesis as well as 
replacement of the nucleus are now used for treatment of chronic back pain after disc 
herniation.11,12,13,14,15,16,17  So far, no clinically established procedure is available that slows 
down the progression of degeneration. In this context, the question about the ability of the 
intervertebral disc to regenerate intervertebral disc cellular matrix subsequent to discectomy 
has been raised.   
Repair of mild degeneration of the disc at the time of herniation, and regeneration of disc 
matrix following discectomy and transplantation of a variety of in vitro derived cell lineages has 
been proven in animal models.18,19,20  It has similarly been shown that transplantation of similar 
cells into traumatic lesions of the knee, results in possible regeneration of cartilage.21,22 
In the present study, regeneration of vertebral disc matrix will be assessed as an allograft 
transplant.  Based on a proprietary technology developed at UMTB (Vivex, Inc.; Marietta, GA, 
USA) that retains active cells shown to offer regenerative potential and pairs them with donor-
derived nucleus pulposus, a formulation has been aligned to supplement degenerative disc 
changes with the potential for better mechanical performance and presumably physiologic as 
well. The cells supporting this product are capable of differentiating into multiple lineages 
including disc chondrocytes given appropriate conditions and stimulating factors. 23,24,25 

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4.1 
In-vitro studies 
In vitro cultivation of intervertebral disc cells as a monolayer has been performed by several 
investigating groups18,26,27 using different media.  It was reported, that intervertebral disc cells 
were able to proliferate in vitro and regained their chondrocyte-specific properties after 
contact with collagenous media. 28,29  This led to the assumption, that in vitro expanded 
intervertebral disc cells could be transplanted into the disc and perhaps integrated into pre-
existing collagenous structures. 
4.2 
Pre-clinical studies 
An early (circa 1999) pre-clinical study in a rodent model showed that transplantation of 
autologous nucleus pulposus cells that had been activated by co-culture with annulus fibrosus 
cells into degenerated discs in rabbits, delayed the formation of clusters of chondrocyte-like 
cells, the destruction of disc architecture, and the elaboration of type-II collagen. 30  This early 
study has led to many more recent attempts, using improved techniques, different models, and 
both autologous and allogeneic cell lines, to prevent further disc degeneration subsequent to 
discectomy. Clearly the advantage of exposing naïve cells with full differentiation capacity to 
appropriate guidance towards a specific phenotype is the direction and dimension intended. 
Ganey and Meisel 31 in cooperation with the Emory Spine-Center in Decatur, Georgia (USA) 
removed intervertebral disc material (segment L1/L2, L3/L4) from 18 dogs while leaving 
segment L2/L3 unchanged.  Subsequently, transplantation of cultured autologous disc-derived 
chondrocytes (ADCT) into the intervertebral disc (segment L3/L4) was performed to investigate 
the hypothesis that autologous disc chondrocytes could be used to repair damaged 
intervertebral disc.  Comparisons between the untreated degenerated disc (L1/L2), the normal 
intervertebral disc (L2/L3), and the disc level that had received the ADCT transplantation (L3/L4) 
were conducted over a 12-month period.  The transplanted cells were integrated into newly 
developed extracellular matrix, produced an extracellular matrix that displayed composition 
similar to normal intervertebral matrix, and when the disc heights were analyzed for variance 
according to treatment, a statistically significant correlation between transplanting cells and 
retention of disc height was achieved.  A good correlation was found between the 
macropathological results and the x-ray and MRI results.  
These results led to the conclusion that progression of degeneration of the lumbar disc after 
operation can be prevented by transplantation of in vitro cultivated disc-derived cells into the 
intervertebral space and that the MRI is a suitable non-invasive method for evaluation of the 
changes. 

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Further work elaborated the use of non-cultured cell lines, or adipose-derived regenerative 
cells, in repairing the intervertebral disc following partial discectomy in dogs.32  This study was 
designed to evaluate the safety and performance of adipose-derived regenerative cells (ADRCs) 
injected into the canine spine six weeks post discectomy to engraft in the vertebral discs, to 
stimulate disc matrix deposition, and to enhance recovery by delaying further disc 
degeneration as measured by imaging, macroscopic and microscopic techniques as well as 
molecular biology assessments of proteins.  The study concluded that the treatment of 
intervertebral discs with ADRCs in hyaluronic acid is safe and effective in this canine model of 
intervertebral disc injury that mimics clinical patients undergoing discectomy after herniation. 
ADRC treated discs in this study closely resembled healthy control discs at 6 and 12 months 
based on pathology as well as based on measurement of matrix protein amounts.  ADRCs 
remained viable over the 12-month study period and stimulated significant increases in 
aggrecan and type-II collagen, two critical components comprising a normal disc matrix. 
4.3 
Clinical studies 
In the first clinical approach in man, 8 patients suffering from traumatically caused disc 
herniation were chosen for an individual treatment (unpublished data, Meisel, Ganey, et al.).  
All patients underwent a sequestrectomy.  Protruded disc material or cells that were removed 
during discectomy were used for in vitro proliferation.  Five of the 8 patients received an 
autologous transplantation of the proliferated disc derived cells 3 months after discectomy.     
One aim of this pilot study was to prove that the disc that underwent discectomy was healed 
after 3 months therefore ensuring that the transplanted ADCTs would not pass out of the disc.  
This was confirmed by utilizing a standardized volume pressure measurement that is commonly 
used during chemonucleolysis.33 
As no statistical analysis was planned for these individual attempts, individual case control 
observations were performed in order to investigate the methodological and medical 
questions.  After a mean duration of follow-up of 8.2 months (1 - 18 months), the 5 patients 
who received an ADCT transplant were completely free of complaints, working fulltime and had 
resumed sports activities.  First analyses of the MRI data showed no decrease in intervertebral 
height, no disc desiccation and no degenerative changes of the adjacent vertebral endplates.  
These results correlate well with the results of the pre-clinical rodent model. 
The promising results of this pilot study led to EuroDISC, a prospective, randomized, multicenter 
clinical trial designed to assess the long-term efficacy of ADCT in a broader population that was 
initiated in 2002.  From that study, 109 patients were followed and an interim of the results 
summarized as follows: 

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1. 
The annulus had healed sufficiently 12 weeks after discectomy to allow for a 
successful transplant. 
2. 
The transplant was achieved by a minimally invasive percutaneous injection. 
3. 
Patients receiving cells had greater pain reduction. 
4. 
Discs in patients receiving cells had a significant difference in fluid content. 
5. 
Adjacent discs also demonstrated a difference in fluid content.  
The results of the pre-clinical and clinical studies described above, provide the confidence that 
the transplant of ADCTs post-discectomy could be a viable treatment with long term effect and 
improvement over the standard of care. 

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5 
RATIONALE 
Since 1991, several investigating groups have shown using in vitro and in vivo analyses, that 
degenerative changes of the intervertebral disc can be retarded, or positively influenced within 
the meaning of repair of the annulus fibrosus and the nucleus pulposus. 34,35  The clinical 
relevance of these investigations is still under discussion. 
The aim of the VAST trial is to investigate the clinical relevance of the repair of intervertebral 
disc tissue by a supplementary transplantation of cellularized allograft disc matrix in a 
controlled clinical study, or continued treatment with conservative, non-surgical intervention. 
The clinical differences between the three groups will be compared by analyzing pain, 
functional restrictions and efficiencies of the lumbar spinal column, and neurological deficits 
using different scores that were especially developed for the assessment of degenerative back 
complaints.5,36,37,38,39  Additionally, X-ray and MRI will be performed in order to compare the 
morphologic changes between the active allograft treatment, placebo treatment and 
conservative care treatment groups.  Evaluations of X-ray and MRI will include changes in the 
height of the intervertebral disc, modic changes of the adjacent endplates and the fluid content 
of the operated intervertebral disc.40,41  
The main target of this new method is to slow down the complex degeneration process of the 
intervertebral disc that often increases after operation of the disc and to offer prescriptive 
option to therapeutic intervention that is clinically relevant and economically efficient.42 
All previous and current human studies of transplanted cells, have involved the use of 
autologous or allogeneic cells that required ex vivo expansion of the cells, which is costly, time-
consuming and strictly regulated, making it an intricate procedure.  By utilizing allograft 
preparation technology refined by UMTB through minimal manipulation of the tissue and cells, 
strict regulatory issues are circumvented.  Clinical costs may also be reduced, as the number 
and duration of hospital admissions may be diminished, and the need for expensive stem cell 
culture facilities is eliminated.   
A variety of autologous ADRCs have been tested and are being utilized in a variety of indications 
in the clinic including breast reconstruction surgery subsequent to mastectomy,43,44,45 cosmetic 
surgery of the face46,47 and breast,48 and both acute49 and chronic50 cardiovascular disease.  While 
the mechanism of action remains to be fully elucidated, pre-clinical studies indicate that a variety 
of cells transplanted into the disc are capable of generating extracellular matrix and providing 
the necessary cellular components required to prevent further disc degeneration following 
discectomy. Cells aligned to this study and supplementary allograft material offer confidence in 

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differentiation towards a nucleus pulposus phenotype, therefore, it is warranted to conduct this 
study and to confirm this technology in a controlled, safe, and regulated environment. 
To minimize patient risk, the first 24 patients (at least 4 from each group) will have an 
additional clinic visit one month after transplantation and will undergo a full safety assessment; 
including X-ray and MRI (see Appendix A).  All data collected up to and including this point in 
the study will be collected and reviewed by the Steering Committee, who will determine if 
patient recruitment can continue.  The parameters used by the Safety Committee to determine 
whether recruitment can continue, will be pre-defined in a separate document but will include 
the following: 
1. A comparison of the adverse event (AE) profile between the three groups including rate, 
relationship, and severity. 
2. A comparison of the clinical laboratory parameters between the three groups. 
3. A comparison of vital signs and physical examination findings between the three groups. 
4. A comparison of X-ray and MRI findings between the three groups. 
 

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6 
STUDY DESIGN 
This is a, prospective, randomized, parallel-arm, multicenter study that will enroll up to 220 
evaluable patients at up to 20 clinical sites.  The outcomes of this trial will be based on 
assessment of primary and secondary endpoints at 6 and 12 months after treatment of 
supplementary allograft compared to conservative care in subjects who have pain attributable 
to disc degeneration as judged by MRI scoring (Pfirrmann), physical examination, and patient 
reported pain. Optional long term follow up at 24 and 36 months for all randomized subjects 
will allow for additional secondary endpoints to analyze pain.  
The study is composed of three phases – the Screening Phase (enrollment), Active Phase (12 
months) and the optional follow up period (additional 24 months).  As outlined in Figure 1, 
there is an indeterminate overlap of up to 14 days between the end of the Screening Phase and 
the start of the Active Phase for individual subjects in order to evaluate the protocol, and 
consent to their participation.  After completing the Informed Consent procedure, screening 
and study specific procedures can be performed. Only patients that meet the entry criteria for 
both phases are eligible and can participate in this study.   
During the 14 days of the Screening Phase (Day -14 to Day 0), patients will be assessed for study 
eligibility to establish their baseline condition, and will be randomized to either conservative 
care (maintaining current level of care), or be provided with supplementary allograft 
transplantation (Day 0 of the Screening Phase), or receive placebo treatment (saline). All 
patients who are randomized to conservative care in the Screening Phase (Day -14 to Day 0), 
will be evaluated as per standard of care and will be assessed along with those who are 
selected for eligibility to enter the Active Phase of allograft transplantation.   
The first 24 subjects randomized (at least 4 subjects from each group) will return to the clinic 
for a safety assessment 1 month after treatment.  Subsequent clinic visits will occur at 6 and 12 
months following treatment for safety and efficacy assessments.  Subjects randomized to 
conservative care will additionally receive a clinical follow-up at 3 months to assess pain, 
change, or loss of function since their initial visit. 
Optional long term follow up at 24 and 36 months for all randomized subjects will allow for 
additional secondary endpoints to analyze pain. Subjects who wish to participate in the long 
term follow up will reconsent with the informed consent addendum 2 during an office visit. 
Subjects then will be reassessed for inclusion/exclusion criteria and fill out VASPI, ODI, SF-36, 
and Resource Utilization questionnaires. If eligible for an allograft injection, the PI will perform 
a neurological exam, physical exam, labs, and give the subject applicable questionnaires. An 
MRI and x-ray will be performed on subjects receiving another injection for safety purposes. 

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The 36-month visit can be performed over the telephone by the study coordinator if the subject 
wishes.  
 
Figure 1 – Study Design 
 
6.1 
Study Population 
The study population will consist of approximately 220 male or female patients of any ethnicity 
from 18 to 60 years of age who demonstrate clinical disc degeneration at one or two vertebral 
level from L1 to S1 that would be considered candidates for conservative care, or surgery.  
Patients must be classified with moderate to severe disability (ODI ≥40%) and chronic pain 
(VASPI ≥40 mm).  Eligible patients must have no contraindications to allograft transplantation, 
have a life expectancy of >2 years, and be willing to return to the clinic for multiple safety and 
efficacy assessments for up to 12 months following enrollment. 
6.2 
Patient Identification and Randomization 
The Informed Consent Form (ICF), signed prior to any study specific screening procedures being 
completed, will provide details on both the Screening Phase and the Active Phase of the study.  
Each patient that signs Informed Consent will be randomized to the active allograft, placebo, or 
conservative care treatment group. The randomization will occur through a secured envelope 
system, during which the subject will be provided with a unique subject identification number 
(XX-XXX, site number-subject number). During the Screening Phase, all subjects randomized to 
active allograft or placebo treatment will be scheduled for a transplantation procedure, while 
the conservative care treatment subjects will be followed as per the routine standard of care.  
       Screening Phase 
      Active Phase 
    
Day 0 
Day -14 
Day 0 
  M1 M3 
 M 6 
    M 12 
Assessment 
Transplant (Enrolled) 

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On or before Day 0 of the Active Phase, the patency of the affected disc will be confirmed, and 
subjects determined eligible from the screening phase who have consented to participation and 
are randomized to allograft treatment will receive the study material.  Patients are considered 
enrolled in the study when they undergo successful treatment in the Active Phase and receive 
either allograft treatment, placebo (saline) treatment, or conservative care treatment.   
6.3 
Blinding 
The assignment to treatment (active allograft, or placebo, or conservative care) is open label at 
Day 0 of the Active Phase to the extent that subjects receiving allograft or placebo will not be 
aware of what they have received, while those assigned to conservative care will be aware. All 
site study staff will be aware of the group to which each subject is randomized. Sites will be 
trained to ensure that subjects receiving the allograft or placebo treatment will remain blinded 
to their treatment throughout the study duration. Subjects will be unblinded during the study 
exit or upon signing of the new informed consent for the study extension.   
6.4 
Treatments administered 
Subjects screened and eligible for the Active Phase of the study will have diagnosis of the 
affected disc to normal standard procedures for all treatment groups.   At the baseline visit (Day 
0) of the Active Phase, eligible subjects who are randomized into allograft or placebo treatment 
will undergo a transplantation procedure.  This procedure will consist of the following: 
1. Transplant supplemental viable allograft into the affected disc 
2. Transplant placebo saline treatment as alternative arm of study. 
These procedures are outlined in detail in Appendices B and C respectively.   
At 24-months, placebo saline subjects and active allograft subjects are eligible to receive the 
allograft injection.  
6.5 
Identity of investigational product(s) 
The product is generated from human allograft nucleus pulposus containing viable cells.  Each 
product is individually prepared but is not specific for the patient being treated.  The details for 
the preparation of cells and supplemental allograft are described in Appendix C.   
6.6 
Selection of the study dose 
A minimum of 6*106 cells will be suspended in 2 ml of matrix (NP). The investigator will ensure 
delivery of the dose available to reach highest possible benefit for the subject, i.e., volume 

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available degenerative disc being patient specific, and subsequent to Pfirrmann scoring, 
desiccation, and volume that can be delivered. 
The volume of material has been derived from previous studies that have shown volume, cell 
density, and deliverability to be important criteria that demonstrate clinical differences. 
Subjects enrolled and randomized to receive the viable allograft will receive one injection of 
approximately 6*106 cells mixed in a 1:1:0.75 by-volume ratio of cells:saline:matrix (NP) 
injected into the center of the affected disc(s) in the location of the nucleus pulposus.  No more 
than 2.0 ml will be available for injection at each level into the nucleus pulposus of the 
symptomatic disc, or discs. 
6.7 
Prior and concomitant therapy 
Prior complaints, surgeries, diagnostics and therapies will be documented concerning the 
affected intervertebral disc and other related diseases and medication. All significant medical 
history (as determined by investigator) must be documented regardless of when it occurred.  
All concomitant medication taken within 30 days prior to obtaining informed consent, and 
taken at any time during the study during both Screening and Active Phases will be documented 
on the case report forms (CRFs). 
6.8 
Treatment compliance 
A lack of compliance during the Screening Phase will result in an exclusion from the Active 
Phase of the study.  Once treatment occurs, a subject can only be excluded from the study due 
to the following: 
1. Withdrawal of consent 
2. Lost- to follow-up  
3. Death 
4. Subject undergoes subsequent surgery on the treated disc 
5. Investigator withdrawal due to subject’s study compliance 
6.9 
Study Duration 
The study duration for all enrolled subjects in this trial is approximately 12.5 months, including 
a 2-week Screening Phase for enrollment following initiation of consent documentation, 12 
months of follow-up after treatment in the Active Phase, and an optional long term follow up 
period of an additional 24 months.  Study enrollment is anticipated to require approximately 3-
6 months.  Therefore, the total study duration will be approximately 39.5 – 42.5 months. 
Subjects who have unremitting pain, or worsening conditions and who had been randomized to 

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the conservative group will be evaluated clinically and be given the option to crossover into the 
allograft supplement group. All randomized subjects will have the option to receive the 
allograft treatment during the optional long term follow up at 24 months. These subjects will fill 
out questionnaires at 36 months and have the opportunity to do so over the phone.  
This study may be terminated by the sponsor if deemed necessary and documented by an 
amendment to this protocol.  If the study is terminated, the sponsor will support follow-up of 
those subjects who entered the study as though the study had not been terminated. 
6.10 
Subject Withdrawal and Replacement 
Subjects may withdraw from the study at any time without penalty and for any reason without 
prejudice to their future medical care.  In all cases, the reason(s) for withdrawal, and the 
primary reason, must be recorded on the appropriate case report form (CRF).  If a subject is 
prematurely withdrawn from the study after randomization (Day 0 of the Active Phase), the 
investigator must document the reason(s) and make every effort to perform a final Termination 
Visit.  The procedures to be followed for the Termination Visit are the same as those defined for 
the Month 12 Visit. 
Subjects that are consented, screened and randomized, but do not undergo a successful 
transplantation (Day 0 of the Active Phase) will be considered screen failures. These 
randomization assignments will be re-used. The randomization and the replacement of subjects 
will be orchestrated through a 3rd party designated independent of the data collection or 
analysis.   

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7 
EFFICACY AND SAFETY MEASUREMENTS 
7.1 
Study Procedure 
In the scope of routine procedures of the investigating centers, each patient with the given 
indication will undergo treatment as defined in the study.  Besides the investigator’s standard 
of care procedure, after being informed about and giving consent to the screening for potential 
participation in the study, the following evaluations will be performed for each patient. 
7.1.1 Screening Phase Day -14 to Day 0 or VS1: 
Potential subjects will be identified and will provide written informed consent for the entire 
study before undergoing screening and study specific procedures.  The investigator or designee 
will check the inclusion and exclusion criteria and collect the patient data and medical history. A 
physical examination will be performed and all concomitant diseases and medication will be 
documented. The scores/scales defined as ODI, VASPI, and SF-36 will be completed by the 
subject, and assisted by the physician or physician designate (as needed), and a “baseline” MRI, 
X-ray, and laboratory evaluation will be performed. All required assessments are outlined in 
Appendix A. VS1 may require multiple clinic visits during this 14-day eligibility screening period.  
Patients will have had disc pain for a minimum of 6 months to be included. Ineligible subjects 
should be identified early in the process and prior to completing an MRI and X-ray. MRI and X-
ray images up to 6 months prior to treatment are acceptable. 
7.1.2 Active Phase Day 0 or VA1: 
The Baseline Visit (Day 0) of the Active Phase will occur for subjects that are consented and 
meet eligibility criteria. MRI/X-ray images performed up to 6 months prior to Day 0 are 
acceptable to be used for eligibility criteria assessment.  Subjects who continue to meet all 
inclusion and exclusion criteria will need to have all baseline questionnaires, scores/scales, and 
additional assessments completed, including concomitant diseases, medication information and 
resource utilization as outlined in Appendix A. All subjects randomized to the allograft or 
placebo treatment groups will have the patency of the affected disc confirmed. Hereafter, 
these subjects will undergo preparation for receiving the supplemental allograft treatment or 
randomized to placebo treatment (saline), or randomized to conservative care treatment.  
 
 

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7.1.3 
  Active Phase 1 Month (± 3 days), or VA2 
The first 24 subjects randomized will return to the clinic at 1 Month (± 3 days) for a complete 
safety assessment including a physical examination, a review of concomitant medication and 
diseases, AEs, and clinical labs.  Efficacy scales/scores will also be completed by the subject, and 
assisted by physician (as needed), and at least 4 patients from each group will be represented. 
All required assessments at 1-month follow-up are outlined in Appendix A. 
7.1.4      Conservative Treatment Group 3 Months (± 14 days), or VA3 
Patients randomized to the conservative arm will be evaluated with VASPI, ODI, SF-36 
questionnaires as well as complete all required additional assessments as outlined in Appendix 
A during the 3 months visit. Patients will be evaluated for deteriorating or improving conditions 
relative to enrollment. Subjects who have experienced a significant decline in condition defined 
as a 10% increase in pain by VASPI, or a 9-point increase in ODI will be offered the allograft 
treatment as a crossover.  If the subject does not meet the aforementioned changes in ODI or 
VASPI, or is considering withdrawal, they may also be offered the allograft treatment by 
physician discretion if condition has significantly declined. Subjects that crossover do not have 
to re-consent. The crossover allograft treatment can occur at any time period after the 3-month 
follow-up visit. To administer the crossover allograft treatment, a new visit will be scheduled 
and this visit will be considered as the new Active Phase Day 0. In addition to the 3 months 
follow-up visit assessments, these crossover subjects will receive a MRI and X-ray prior to the 
allograft treatment. All assessments done at this 3 months follow-up visit will be considered as 
the new baseline assessments. These crossover subjects will receive follow-up visits at 6 
months and 12 months after allograft treatment. Crossover subjects will not be replaced by 
enrolling new patients in the conservative care treatment group. 
7.1.5   Active Phase Month 6 (± 30 days) or VA4: 
All randomized subjects will return to the clinic 6 months (± 30 days) subsequent to treatment 
for all safety and efficacy assessments as outlined in Appendix A.  ODI, VASPI, and SF-36 
questionnaires will be completed by the subject, and assisted by physician or physician 
designee. All subjects (excluding conservative care crossover subjects) will be randomized to 
include MRI at 6-month (MRI or no MRI,  ratio 1:1) follow-up in addition to all other 
assessments. This randomization is performed to assess whether predictability at 6 months 
indicates performance at 12 months. The conservative care subjects that crossover to the 
allograft treatment group will all receive an MRI at 6-month follow-up after allograft treatment. 
All subjects will receive an X-ray at the 6-month follow-up visit. Additionally, a review of 
resource utilization since the Day 0 visit will be completed. 

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7.1.6    Active Phase Month 12 (+ 30 days) or VA5: 
All randomized subjects will return to the clinic 12 months (+ 30 days) subsequent to 
transplantation for safety and efficacy assessments as outlined in Appendix A.  ODI, VASPI, and 
SF-36 questionnaires will be completed by the subject, with assistance from physician or 
physician designee. All subjects will receive an MRI and X-ray at the 12-month follow-up visit.  A 
review of resource utilization through the 12 Month visit will be completed. 
7.1.7    Optional Long-Term Follow Up Month 24 & Month 36 (+ 3 Months) or VA6 & VA7: 
All randomized subjects will have an option to continue to be monitored for long-term follow 
up. Before study procedures begin, the informed consent addendum 2 for study extension will 
need to be signed. At the 24-month in-office visit, subjects will first be reevaluated for 
inclusion/exclusion and fill out VASPI, ODI, SF-36, and Resource Utilization. If eligible for 
allograft treatment, the PI will perform a neurological exam, physical exam, labs, and give the 
subject applicable questionnaires. All randomized subjects will have the option to receive 
allograft treatment at 24 months in accordance with the inclusion/exclusion re-evaluation. An 
MRI and x-ray will be performed on subjects receiving another injection for safety purposes. If 
needed, a second office visit may be scheduled within 14 days of the original evaluation to 
allow appropriate time for the laboratory investigation and MRI. All follow up subjects will 
complete VASPI, ODI, SF-36, and Resource Utilization questionnaires at both follow up visits. 
The 36-month will consist of questionnaires and can be performed over the phone if the subject 
chooses.  
 
7.2 
Appropriateness of measurements 
The Oswestry low back pain disability questionnaire (according to Hudson-Cook) or OPDQ, a 
self-rating scale, will be used to calculate the Oswestry Disability Index (ODI), the primary 
efficacy criterion. The use of this scale in clinical trials is recommended for its acceptable test 
quality and satisfactory test-retest reliability.  
A composite primary endpoint with the ODI as well as a pain score (VASPI) will be used to 
increase the efficiency of this small trial. 
Additionally, the SF-36, an often-used scale to assess patients’ general condition and quality of 
life, and the visual analogue scale of pain intensity (VASPI), a standard to measure general pain 
are used as secondary criteria.  

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Therefore, a number of measurements are used to assess the clinically relevant symptoms in 
intervertebral disc pain as well as functional disability. Additionally, morphological changes will 
be observed by MRI and X-ray. 
7.2.1 Primary efficacy variable 
The reduction of back pain attributable to lumbar disc degeneration, assessed by the outcomes of 
the ODI and VASPI questionnaires, that will be determined for the primary efficacy variable at 6 
and 12 months after treatment . 
7.2.2 Secondary efficacy variables 
Analogous to the primary parameter, the rates concerning the other recorded scores, and the ODI 
at other time points, with different definitions of healing will be analyzed as well. 
MRI will be evaluated with respect to intervertebral height, disc desiccation, adjacent vertebral 
endplate morphology and Pfirrmann grading score. 
An assessment of the tissue repair by X-ray and MRI will be performed by a panel of physicians 
blinded to treatment. 

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8 
INCLUSION / EXCLUSION CRITERIA 
8.1 
Inclusion Criteria 
Patients will be entered into this study only if they meet ALL of the following criteria: 
• Able to provide an English written Informed Consent 
• Age 18 to 60 years inclusive 
• Male or female 
• Body mass index <35 
• Pfirrmann Grade [3-6] 
• Radiographic confirmation by MRI/X-ray of: 
(1) translational instability defined as ≤5 mm, or 
(2) angular instability defined as ≤5° 
• Back pain (with or without radicular leg pain) measured by: 
(3) ODI of at least 40%, and  
(4) VASPI of at least 40mm 
• Pathologic level between L1 and S1 
• 1 or 2 vertebral level involvement that has been evaluated for at least 6 months and treated 
with conservative care 
• Symptomatic back pain attributable to intervertebral disc for a minimum of 6 months 
• No previous surgical treatment at the disc level(s) being considered 
• Psychosocially, mentally and physically able to fully comply with this protocol, and follow-up 
schedule 
• Ability to undergo allograft transplantation 
• Life expectancy >2 years 
• No contraindications to MRI 
• No history of malignancy (basal cell carcinoma) or chronic infectious disease (e.g. HIV, 
Hepatitis) 
• Agree to use appropriate contraception; not planning on becoming pregnant for 24 months 
after treatment 
• Patient disc for transplant confirmed by inter-discal pressure measurement, or disc-imaging 
study. 
• No signs or symptoms of infection 
• No chronic use (>7 consecutive days) of anticoagulants (such as aspirin) or NSAIDs prior to 
treatment   

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8.2 
Exclusion criteria: 
• Seropositive or seronegative spondyloarthropathy  
• Type III Modic changes 
• Prior surgeries of segments between L1 and S1 
• Chemonucleolysis or percutaneous laserectomy of the affected disc prior to the study 
• Chronic facet syndrome 
• Stenosis of the spinal canal that is moderate to severe or more in degree 
• Spondylodiscitis 
• Spondylolisthesis (lysis and degenerative) 
• Severe motor deficit or cauda equina disorder based on investigator determination 
• Congenital abnormalities of the spinal nerves 
• Pelvic and inguinal angiopathy 
• Neurogenic inguinal syndrome 
• Syringomyelia 
• Diastenomatomyelia 
• Traumatic neurological disorders 
• Diseases of the kidney (nephritis, pyelonephritis)  
• Other severe diseases of any other major body system as judged by the investigator 
• Regular intake of systemic steroids 
• Malignant diseases of any solid organ or any hematologic malignancy during the previous 5 
years 
• Patients who have participated in a clinical trial within the last month prior to inclusion 
• Moderate to severe or greater lumbar stenosis of both transplantation endplates and 
adjacent levels  

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MATERIALS AND METHODS 
8.3 
Test Material  
The material used for this study will be a proprietary supplemental cellular allograft nucleus 
pulposus obtained from donors at UMTB.  The tissue will be processed using UMTB SOP and 
provided to participating clinical sites for transplantation.   
8.4 
Study Procedure 
On Day 0 of the Active Phase, eligible subjects will undergo transplantation of supplemental 
allograft, or saline (placebo), or continue active standard of conservative care.  This 
conservative care procedure will not be defined by this protocol however standard practice is 
to be followed by each physician.  All subjects who undergo successful treatment will continue 
in the study and be followed as per the standard of care. Subjects randomized to continuing 
conservative care will be assessed at 3 months, and clinical indices will be assessed. These 
conservative care subjects who have experienced a significant decline in condition defined as a 
10% increase in pain by VASPI, or a 9-point increase in ODI will be offered the allograft as a 
crossover.  If the subject does not meet the aforementioned changes in ODI or VASPI, or is 
considering withdrawal, they may be offered the allograft treatment by physician discretion if 
condition has significantly declined. 
8.4.1 Transplant of supplemental allograft into the affected disc 
All subjects randomized to active allograft will undergo an intervertebral lumbar injection into 
the target disc.  The procedure of injecting the intervertebral disc will involve placing a 22-
gauge needle into the center of the affected intervertebral disc.  No contrast will be used prior 
to the injection of the supplemental allograft and 1mL of cells (approximately 6*106 cells) 
mixed in a 1:1:0.75 by-volume ratio (Cells in cryoprotectant: Saline: NP) will be injected into the 
center of the affected disc(s) in the location of the nucleus pulposus. At least 1.5-2 milliliters of 
the resulting mixture will be available for injection into the nucleus pulposus of the 
symptomatic disc. Volume injected will be recorded. 
Vital signs will be recorded prior to injection. The treatment injection should be carefully 
controlled. The injection procedure MUST be stopped if any of the following occur:  
• The investigator cannot accurately place the needle tip in the nucleus pulposus  
• The subject becomes hemo-dynamically unstable during the injection procedure.   
 
 

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The following information regarding the treatment procedure must be documented:  
▪ Procedure start and stop time 
▪ Treatment administration stop time  
▪ Treatment interruption information, if applicable  
▪ Total volume of treatment injected  
▪ Pain on implantation 
▪ Anesthesia type(s) 
 
The information collected above will also be collected during the placebo cross over visit.  
8.5 
Assessments 
• Informed Consent will be obtained between Screening Day -14 and Active Day 0, prior to 
any study procedures being performed. The addendum for optional long term follow up 
will be collected before procedure and questionnaires are performed.  
• An assessment of eligibility using the inclusion and exclusion criteria will be conducted 
starting at Day -14 of the Screening Phase.  Prior to randomization at Day 0 of the 
Screening Phase, eligible subjects must meet all inclusion criteria and no exclusion 
criteria for the Active Phase. This will also be assessed after the ICF addendum for long 
term follow up is collected to determine if the subject is still eligible.  
• Medical History and Patient Demographics will be recorded during the Screening Phase. 
• An abbreviated Physical Examination will be done in the Screening Phase within the 2 
weeks prior to transplant, as well as at Month 6, and 12, and at 3 months for the 
subjects randomized to continue conservative care. This will be done for subjects 
completing the placebo crossover injection as well.  
• Resource utilization data (lost time from work, number and kind of previous surgeries, 
duration of complaints (preoperatively), duration of rehabilitation, complications, 
additional physician visits, etc.), will be obtained during the Screening Phase as a 
baseline to similar data obtained during the Active Phase at Months 6, and 12. This will 
also be collected during the long term follow up visits of 24 and 36 months.  
• Physicians clinical assessments will be collected in the Screening and in the 2 weeks 
prior to transplant, and in the Active Phase at Months 6, and 12, and in the conservative 

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care patients at 3, 6, and 12 months. A neurological exam will be completed before 
placebo crossover additionally.  
• Patient self-assessments including VASPI, ODI, and SF-36 will be collected at every 
scheduled clinic visit. VASPI, ODI, and SF-36 will be collected in person at 24 months and 
at the 36 month interval, these questionnaires can be performed over the phone during 
optional long term follow up.  
 
 

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• MRI evaluating the intervertebral height, adjacent endplates, deprivation of fluid and 
Pfirrmann score will be obtained during the Screening Phase and in the 2 weeks prior to 
transplant, and in the Active Phase at 12 months. Subjects will be randomized, yes or no 
( 1:1 ratio), to receive an MRI at 6 months. Conservative care subjects that crossover to 
the allograft treatment group will all receive an MRI at 6-month follow-up  after 
allograft treatment.  
• X-rays will be performed static (standing), anterior-posterior and lateral in the Screening 
Phase prior to transplant.  After transplantation, during the Active Phase (Months 6, and 
12) a static and an additional dynamic (flexion/extension) X-rays will be performed. 
• Adverse Events (AEs) and Serious Adverse Events (SAEs) will be recorded once the 
patient is enrolled (Day 0 of the Active Phase).  A detailed discussion of AEs and SAEs is 
located in Section 14.  Optional checkup evaluations will be performed in the case of 
complications. Failure of treatment defined as the necessity of a follow-up operation 
will be documented separately. 
• Laboratory investigation will be conducted according to the routine procedures of each 
investigational center. The valid normal ranges including the methods for all parameters 
will be provided to the sponsor prior to the start of the study.  Only laboratory values 
outside the normal range will be evaluated and commented upon by the investigator. 
The following parameters will be determined: 
 
Hematology: 
 
Clinical Chemistry: 
 
- hemoglobin 
 
- creatinine 
 
- hematocrit 
 
- alkaline phosphatase 
 
- erythrocytes 
 
- AST/SGOT 
 
- leukocytes 
 
- ALT/GPT 
 
- thrombocytes 
 
- -GT 
 
- erythrocyte sedimentation rate  
- glucose 
 
Coagulation: 
 
- PTT 
8.6 
Study Schedule 
The Study Schedule with all required assessments is listed in Appendix A. 

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9 
STUDY OBJECTIVES AND ENDPOINTS 
9.1 
Objective 
The primary objective of this study is to evaluate the safety and efficacy of viable allograft 
transplantation for the treatment of patients with symptomatic disc degeneration and tissue 
loss. There will be three treatment groups: (1) supplemental viable allograft treatment, (2) 
placebo (saline) treatment, and (3) conservative care treatment. 
9.2 
Primary Endpoint 
The primary efficacy endpoint of the study is improvement in the ODI at 6 and 12 months after 
treatment, and improvement in Visual Analogue Scale of Pain Intensity (VASPI) at 6 and 12 
months after treatment. 
9.3   
Secondary Endpoints 
Secondary parameters of efficacy will include the ODI, the SF-36, and the VASPI following 
treatment.  Structural outcomes will be assessed using X-ray and MRI measurements at the 
same time points.  Safety will be assessed by the incidence and severity of AEs and clinically 
important changes in laboratory tests. 
A correlation of the clinical results (scores and scales) and the morphological results (X-ray, 
MRI) will be evaluated. All additional efficacy and safety data will be analyzed descriptively. 
The effect supplemental allograft transplant on resource utilization, i.e., days off work, 
subsequent surgeries, other clinic visits will also be measured and compared 
 
 

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10 
RISKS 
10.1 
Transplantation Risk Management 
There are certain known risks associated with lumbar disc injection, expected risks with 
products that are used in the production of the viable allograft. These risks include the 
administration of viable cells may elicit immunogenic and/or inflammatory responses 
resulting from exposure to the donor cells and/or manufacturing content. To date no 
clinical signs or symptoms have been associated with the development of antibodies to 
HLA, NP matrix, or cryopreservative material. To this procedure, there are no xenogenic 
components included in the production of the viable allograft product. 
10.2 
Overall Study Risk Management 
• The following measures implemented by the investigator will minimize the risks 
associated with subjects’ participation in this study: 
PI is careful in selection of personnel (including clinical investigators at the sites) with 
extensive experience in conducting clinical studies and in procedures such as 
provocative disc evaluation, and percutaneous delivery. 
• PI and study staff follow the study protocol, and the PI ensures that all study staff are 
trained and have a strong knowledge and understanding of the clinical protocol, 
including patient selection criteria and procedure requirements 
• PI ensures that the investigators are trained on the procedure requirements in the 
protocol. 
• PI and study staff carefully follows patient eligibility criteria for the investigation to 
ensure that only properly selected patients are being enrolled and treated. 
• The protocol is designed such as patient treatment and follow-up procedures will be 
consistent with those of the established treatment options for the selected patient 
population; all subjects will receive standard of care treatment 
With these risk minimization procedures in place, associated risks of interventional 
procedures in all subjects are expected to be minimal and acceptable. 
 
 

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11 
BENEFITS 
While benefits from participation in this study cannot be guaranteed, it is expected that 
supplemental transplantation will improve the long-term outcome in subjects who have disc 
disease by providing mechanical stabilization, biochemical subsidization, and cellular 
components to sustain matrix viability. 

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12 
RISK / BENEFIT ANALYSIS 
Both pre-clinical and early clinical results of in vitro generated disc-derived cells transplanted 
into the intervertebral disc space in lieu of, or subsequent to discectomy are promising, thus 
raising the need for a standardized, well designed clinical trial. Based on prior results for 
individual patients treated with the surgical standard of care plus in vitro generated disc-
derived cells, a reduced rate of degeneration after herniation would be expected with the 
inclusion of an autologous stem cell transplant. Statistical differences have also been defined 
for levels adjacent to those treated that were correlated with Oswestry disability and quality of 
life indices. 
No clinical data exist in this patient population receiving a transplant of allogeneic donor-
derived viable matrix.  Therefore, the documented risks are those associated with the 
procedures.   
The risks for this procedure include hematoma, epidural bleedings, infections (from local 
infections up to spondylodiscitis and/or meningitis), neurological deterioration as serious as 
lesions of the cauda equina (paraplegia secondary to ascending bleeding or infection), paresis, 
sensory disturbances, disorder of potency or disorder of sexual sensibility, cerebrospinal fluid 
fistula, retroperitoneal lesions (large vessels, ureter, intestine), instability of the vertebral 
column, relapsing herniation, incomplete improvement (paresis, sensory disturbances), bladder 
or bowel dysfunction and recurrence of complaints, in particular pain. 
So far, no additional risks due to the application of autologous in vitro generated chondrocyte 
suspension, or matrix carrier itself have been documented. In more than 700 documented 
cases of autologous stem cell transplants (mainly applied to the knee) similar to the procedure 
to be followed in this trial, no immunoreaction to the transplant was registered. Furthermore, 
no infectious reactions to autologous cell transplants have been reported in the literature so 
far.   
The volume supplement of the intervertebral disc space performed in the application of the 
cell-suspension, comprises no additional risks as no additional intervention will be done to the 
patient.  
In summary, on the basis of today’s knowledge of either autologous cell or expanded allogeneic 
cell transplantation, the risks associated with the therapeutic approach to be utilized for each 
individual patient is acceptable in the scope of the expected, but yet to be proven clinical 
benefit. 

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13 
DATA ANALYSIS 
13.1 
Data Management 
13.1.1 Data collection 
The outcome of all data collected during each follow-up visit according to Appendix A for the 
three treatment groups will be documented on the study-specific Case Report Forms (CRFs).  
For all visits and for each patient, CRFs will be completed and all results will be forwarded to 
Vivex Biologics, Inc. or designated representative for data management and analysis after 
source data verification by the responsible monitor has been completed. 
13.1.2 Database management and quality control 
Logical and statistical plausibility checks will be performed on all data entered into the 
database. All data which are used for the analysis will be documented in individual data listings.  
13.1.3 Interim analysis 
For safety and efficacy reasons, interim analyses are planned to be performed after the first 24 
subjects have completed the Month 1 assessment of the Active Phase.  This analysis will be 
performed in a descriptive manner only and no un-blinding will occur unless a safety signal is 
evident. A Steering Committee will be convened to review the results of the interim analysis.  A 
similar review will occur when they complete the Month 6 assessment of the Active Phase, 
where primary endpoints of pain and ODI, and randomized MRI will be available for analysis. 
13.2 
Statistical Methods and Determination of Sample Size 
13.2.1 Populations for analysis 
Statistical analysis will be done for the ITT and PP population should be last observation carried 
forward (LOCF). 
13.2.2 Statistical and analytical plans 
The statistical evaluation will be done using appropriate statistical software packages. 
For all baseline data, descriptive statistics will be presented. In the case of continuous 
parameters, statistical parameters for location and dispersion (e.g. n, mean, standard deviation, 
range) will be calculated. For discrete data, appropriate frequency tables will be produced. 
 
 

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Primary criteria: 
The primary criteria will be analyzed in a confirmatory way using a two-sided approach on an -
level of 0.05 based on the total score. A hierarchical test procedure will be applied. In the first 
step the pre-post difference of the groups will be compared using Wilcoxon rank-sum-test. 
In case of a significant result a responder analysis will be done in the following way: 
For each number r = 1, ..., 10 the subjects will be categorized as responders, if the pre-post-
difference is greater or equal r. The corresponding contingence table will be tested using 
Fisher’s exact test resulting in a p-value pr. 
The pr will be sorted and the Bonferoni-Holm procedure on a 5 % level will be applied. 
Secondary criteria: 
All secondary variables will be analyzed in an exploratory way using adequate statistical 
procedures. The subscales of ODI may be analyzed separately using the same procedure as for 
the total score of OPDQ. To support the validity of OPDQ the correction of OPDQ with QUE will 
be done. 
13.3 
Sample Size Considerations 
The primary criteria will be analyzed using Wilcoxon rank-sum-test. Based on Fairbanks, 200051, 
Hudson-Cook, 198936 and Fritz, 200152 a common standard deviation  = 15.5 score points can 
be assumed. 
Fritz, 2001, calculated a Minimum Clinically Important Difference of 6 score points. Reliability is 
reported in the literature in the range of 0.75 - 0.91. Worst case using the standard deviation 
above results in a measure error of 7.75 score points. Thus, we assume a clinically relevant 
difference of 9 score points. Under this assumption the probability p (x < y) = 0.341 (x, y 
observations in the groups, respectively). A sample size of 40 in each group will have 80 % 
power to detect a probability of 0.341 that an observation in one group is less than an 
observation in the other group using Wilcoxon rank-sum-test with a 0.05 two sided significance 
level (calculations are done using nquery 4.0). 

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14 
ADVERSE EVENTS / SERIOUS ADVERSE EVENTS 
14.1 
Adverse Event 
According to GCP, an adverse event is defined as any untoward medical occurrence in a patient 
or clinical investigation subject who was treated with an investigational device, and does not 
necessarily have a causal relationship with the treatment or device.  An adverse event (AE) can 
therefore be any unfavorable and unintended sign, symptom, or disease, whether or not 
related to the investigational device.  
For this study, all AEs (including expected and unexpected AEs) and SAEs will be captured in the 
CRF. Adverse events (AEs) occurring during the Screening Phase will not be collected. Expected 
AEs are those that are listed below as known risks, including those described in this protocol, 
the study Informed Consent, the allograft instructions for use, and any procedural (surgery and 
anesthesia) informed consent signed by the patient for the diagnosis, and/or transplant: 
• Immunological response 
• Transmission of disease of unknown etiology 
• Transmission of infectious agents ( including but not limited to: HIV, hepatitis, syphilis, 
or microbial contaminants. 
• Inflammatory response 
• Development of tumor 
• Hematoma,  
• Epidural bleedings,  
• Infections (from local infections up to spondylodiscitis and/or meningitis),  
• neurological deterioration as serious as lesions of the cauda equina (paraplegia 
secondary to ascending bleeding or infection),  
• Paresis, 
• Sensory disturbances,  
• Disorder of potency or disorder of sexual sensibility,  
• Cerebrospinal fluid fistula, 
• Retroperitoneal lesions (large vessels, ureter, intestine),  
• Instability of the vertebral column, 
• Relapsing herniation, 
• Incomplete improvement (paresis, sensory disturbances),  
• Bladder or bowel dysfunction  
• Recurrence of complaints, in particular pain. 

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14.2 
Serious Adverse Event 
Serious Adverse Events (SAEs) are defined as any untoward medical occurrence that: 
• 
Results in death, or 
• 
is life-threatening, or 
• 
requires inpatient hospitalization or prolongation of existing hospitalization, or 
• 
results in persistent or significant disability/incapacity, or  
• 
is a congenital anomaly/birth defect (in an offspring), or 
• 
is an important medical event(s) that may not be immediately life-threatening or 
result in death or hospitalization but that may jeopardize the patient or require 
intervention to prevent one of the above outcomes 
Medical and scientific judgment should be exercised in deciding whether a case is serious and 
whether expedited reporting is appropriate.  All SAEs will be captured in the CRF. 
14.3 
Serious Unanticipated Adverse Device Effect  
A serious unanticipated adverse device effect (SUADE) is defined as any SAE on health or safety 
or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
14.4 
Procedures for AE Reporting 
All AEswill be recorded by the investigator or designee on the appropriate CRF.  The investigator 
will evaluate the relationship of the AE to the transplant, the device, and study procedures as 
related, not related, or unknown, and will record the findings, including all pertinent details of 
the event on the AE CRF. Adverse events (AEs) occurring during the Screening Phase will not be 
collected. 
The investigator will report any SAE (including SUADEs) occurring during this study to the 
sponsor designated representative within 24 hours of first identifying the SAE.  The designate 
will notify the sponsor Medical Monitor immediately (within 24 hours) and the committee that 
approved the protocol within 10 calendar days or in accordance with the conditions of the MEC 
approval.  The investigator will take appropriate measures to ensure the patient’s optimal care 
and will document these measures on the appropriate CRF.  

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All UADEs will be reported to the sponsor and the reviewing EC within 10 working days of the 
study site becoming aware of the events  
All AEs experienced by a patient will be monitored until the event has resolved, or has 
established a new chronic baseline, or until there is a satisfactory explanation for the changes 
observed, or until the patient is lost to follow-up.  

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15 
REGULATORY OBLIGATIONS 
15.1 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 
Before the beginning of the trial, the protocol will be submitted to the appropriate Ethics or 
other authoritative Committees of the principal investigator.  The study will only be performed 
when a full approval of this protocol has been obtained from the appropriate committee(s). 
Additionally, the protocol will be submitted to the Ethics Committees of the test centers 
involved. Any amendments to the protocol will be submitted to the Ethics or other 
authoritative Committees. 
Documentation of the date of the meeting, constitution of the committee and voting members 
present at the meeting will be requested by the sponsor/CRO.  
The approval will be submitted to the appropriate competent federal higher authority together 
with a copy of the study protocol, blank CRFs and informed consent. In case of a positive 
approval the study can be started immediately.  
Ethics Review Committees (ERC) must be constituted according to the law and guidelines and 
Authority Approval. 
This protocol will be submitted to the appropriate Committee or Board and their written 
unconditional approval obtained and submitted to the sponsor before commencement of the 
study. 
15.2 
Informed Consent Process 
Prior to the administration of any tests or procedures required in this protocol for either the 
Screening or Active Phase, the investigator or designee will obtain informed consent in writing 
from all potential subjects considered for entry into this trial.  Each patient must sign and 
personally date the informed consent.  Copies of the informed consent will be retained in the 
medical record and the subject’s study binder.  A copy of the signed informed consent will be 
given to the subject to take home.   
The consent form and as necessitated by local law, an additional patient information leaflet for 
study participation, will explain the nature of the study, its objectives and potential risks. 
Furthermore, it will detail the requirement of the participant, the trial treatment and the 
probability for random assignment to each treatment group, all trial procedures, alternative 
procedures and the fact that he is free to withdraw his consent at any time without reason.  
Details of indemnity and insurance are also attended with assurance. 

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As required by ICH-GCP the subject will give in writing his authorization that the study data may 
be given for review to the responsible authorities, and that the monitor will be granted direct 
access to the subject’s original medical records for verification of clinical data.  
Notification to Authorities 
The study protocol together with the investigators’ names, the investigation sites and the votes 
of the Ethic Committees will be presented to the responsible health authorities and retained by 
the sponsor. 
15.3 
Steering Committee 
A Steering Committee will be established for the conduct of the study with the purpose to 
observe the course of the study and to ensure the highest possible safety for each participating 
patient.  The data to be reviewed, and the timing of the review/s, will be defined in the Steering 
Committee mission and guidance documents. 
In particular, the Steering Committee will receive the 1-Month data for the first 24 randomized 
patients and will determine based upon this information if the recruitment of the remaining 
196 subjects can continue. Participants in the steering committee will include Dr. Randolph 
Bishop, MD, a neurosurgeon, and Dr Chris Hancock, MD, an interventional radiologist, and be 
chaired by H Thomas Temple, MD, Chief Medical Officer for Vivex Biologics, Inc. 
15.4 
Site Selection and Qualification  
A qualification and selection visit will be performed to evaluate site facilities, investigator 
qualifications, adequacy of staffing, and understanding of clinical and regulatory requirements. 
15.5 
Site Initiation 
All investigators and appropriate study staff will be required to participate in an investigator 
meeting which will provide training to all sites at one time or if applicable onsite training in 
order to provide orientation and training regarding the device operation and applicable 
procedures, protocol and CRFs. Physicians and office staff necessary to execute the trial will be 
trained to the composition of the test article, to the history of the implant in intervertebral disc 
therapy, and then provided a laboratory course in preparation of the allograft which will 
include mixing, placement in syringe, and delivery into the center of the disc. Injected discs will 
be imaged, planed with a band saw (if at UMTB facility), and distribution confirmed to depict 
the intended distribution of the material in a clinical setting. 

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15.6 
Monitoring 
During the course of the study, the sponsor or designee may make site visits to review protocol 
compliance, perform source data verification, assess test article accountability, and ensure 
compliance with pertinent regulatory requirements. All review of medical records will be 
performed in a manner to ensure that patient confidentiality is maintained. 
Satisfactory verification of CRF completion, source document verification and query resolution 
may be required to monitor the progress of the study.  Moreover, regulatory authorities may 
wish to carry out such source data checks and/or on-site audit inspections with reasonable 
notification to the study site.  Direct access to source data will be required for these inspections 
and audits; they will be carried out giving due consideration to data protection and medical 
confidentiality.  
15.7 
Required Reports 
The following reports are required of the investigator: 
• 
Reports to Pharmacovigilance (appointed by Sponsor) of any SAEs immediately or at 
least within 24 hours of the study site becoming aware of such events 
• 
Reports to the sponsor and the reviewing EC of any UADEs within 10 working days of 
the study site becoming aware of events (unless the UADE is a serious event, in which 
case it must be reported to the sponsor immediately or at least within 24 hours of the 
study site becoming aware of such events) 
• 
Report to the sponsor, within 5 working days, of withdrawal of approval by the 
reviewing EC or regulatory authority 
• 
Progress reports to the sponsor, monitor, and the reviewing EC at regular intervals (at 
least yearly) 
• 
Report to the sponsor and the reviewing EC of any deviation from the protocol to 
protect the life or physical well being of a patient in an emergency situation.  Such 
notice will be given as soon as possible, but in no event later than 5 working days after 
the emergency occurred 
• 
Reports of any study procedure(s) being performed without prior written informed 
consent being obtained.  Such notice will be given to the sponsor and the reviewing EC 
within 5 working days of the study procedure(s) being performed 

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• 
Final report submitted to the sponsor and the reviewing EC as soon as possible, but no 
later than 3 months, after the conclusion of the study or the conclusion of the 
investigator’s participation in the study 
• 
Other reports to the reviewing EC as may be required 

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16 
STUDY REQUIREMENTS 
To protect the rights and welfare of subjects, the study will be conducted in conformance with 
the Declaration of Helsinki, the ICH E6 guidelines on Good Clinical Practice (GCP), and/or the 
laws and regulations of the participating country, whichever affords the greater protection to 
the human patient. 
All investigators, sub-investigators and study personnel are required to read and follow the 
protocol, as well as any literature that accompanies the products prior to conducting the study 
procedure for the first time.  All investigators participating in this study will be required to be 
trained in the proper use of the study procedures and in the components of this protocol by the 
sponsor. 
The PI is ultimately responsible for the conduct of this study; however, he/she may designate a 
member or members of his/her staff to assist with the collection of data and completion of 
CRFs.  The designee(s) will be documented on an authorization form that is signed by the PI and 
kept in the Regulatory Binder, to be updated as necessary. 
Obtaining informed consent in accordance with national policy is mandatory for patient 
participation.  All patient data is kept confidential and procedures will be implemented to 
ensure that patient confidentiality is not compromised. 
If alternative consent materials are used, they must be approved by Vivex Biologics, Inc. at the 
clinical site prior to use.  Documentation of the approved informed consent must be provided 
to Vivex Biologics, Inc. prior to study commencement at the clinical site. 
After Informed Consent has been obtained, all screening procedures have been performed, and 
eligibility for the study has been confirmed, the subject will be considered enrolled in the study.  
After this point, the reason(s) must be documented on the CRF for any patient who has 
dropped, withdraws, or for any reason cannot complete this study. 
16.1 
Quality Assurance 
All data concerning the study will be documented on the patient’s medical record and on CRFs 
designed especially for this study, or on data clarification forms (DCFs) if necessary.  Each CRF 
and DCF will consist of an original plus two copies.  
In line with ICH-GCP guidelines, clinical monitors will arrange regular visits to the trial center(s) 
to check progress with the study and to collect completed CRFs. One copy will remain in the 
study center, the original will be passed to Vivex Biologics, Inc. or designated representative for 
data management. The original will be send to the sponsor at the end of the study. Until then, 

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the originals will remain at Vivex Biologics, Inc. or designated representative for data 
management. The CRFs will be checked for completeness and plausibility by the clinical 
investigator and the monitor (manually) as well as by Vivex Biologics, Inc. or designated 
representative for data management. 
In addition, the representatives of the Clinical Quality Assurance department at the sponsor, of 
the CRO, and of regulatory authorities, are permitted to inspect the study documents (Study 
Protocol, Case Report Forms, study medication, original medical records/files). All patient data 
shall be treated confidentially.  
In order to guarantee that the performance of the study is in accordance with the ICH-GCP 
stipulations, in-house and on-site Audits may be carried out. Study protocol and final report will 
be additionally examined by the Quality Assurance Unit of the sponsor and/or Vivex Biologics, 
Inc. or designated representative for data management.  
The investigator agrees to give the auditor access to all relevant documents for review. The 
same applies in case of an inspection the authorities. 
After every on-site audit the investigator will receive an audit confirmation by the auditor. This 
has to be filed together with the study documentation and be made available to the authorities 
in case of supervision. At the end of the study, audit certificates will be included in the final 
report. 
16.2 
Monitoring 
It is the responsibility of the investigator to assure that the study is conducted in accordance with 
the protocol and that valid data are entered into the CRF. 
The investigator will permit a representative of Vivex Biologics, Inc. or designated 
representative for data management to monitor the study as frequently as necessary to 
determine that data recording, and transplant handling and protocol adherence are 
satisfactory. The CRFs and related documents will be reviewed in detail in accordance with the 
SOPs of Vivex Biologics, Inc. or designated representative for data management and Good 
Clinical Practice regulations (ICH-GCP). 
In fulfillment of their obligation to the sponsor to verify compliance with this protocol, Vivex 
Biologics, Inc. or designated representative for data management will require that the 
investigator permits the monitor and/or the sponsor’s monitor to review that portion of the 
patient’s primary medical records which directly concern this study. 

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It is the investigator’s obligation to ensure that documentation of all relevant data such as 
medical history/concomitant diseases, date of study enrollment, visit dates, results of 
examinations, administrations of medication and adverse events is correctly entered in the 
patient’s file. 
Vivex Biologics, Inc. or designated representative for data management will affirm and uphold 
the principle of the subject’s right to protection against the invasion of privacy. Throughout the 
study, all data will only be identified by patient number, patient initials and date of birth. 
Anonymity of the data will be maintained in all data analyses. 
All obtained data will be checked for plausibility and completeness by the monitor and in-house 
by Vivex Biologics, Inc. or designated representative for data management.  

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17 
PROCEDURES AND INSTRUCTIONS 
17.1 
Special safety-related procedures 
No special safety-related procedures, other than those attending the risks of surgery, need to 
be defined. In the case of complications/emergency, physicians will use their clinical judgment 
on the best course of action.  All complications related to supplemental allograft 
transplantation will be documented by the physician and will be forwarded to Vivex Biologics, 
Inc. 
17.2 
Administrative procedures 
Vivex Biologicsl, Inc. will be responsible for the supply of Vivex Biologics, Inc. equipment and will 
provide training on the use for the mixture of the supplemental transplant allograft.  A Vivex 
Biologics, Inc. representative will be present for the initial 2 implantations at each site to ensure 
proper procedure is followed.  Once the site has experience in randomization, data collection, 
and allograft delivery as determined by Vivex Biologics, Inc., on-site support will be available on 
request and through a 24-hour phone system.  The interventional procedures will be performed 
by experienced centers and physicians named by Vivex Biologics, Inc. to ensure the highest 
quality of the implantation.  
17.3 
Ethics and Good Clinical Practice 
The study will be conducted in accordance with the ICH Guideline for Good Clinical Practice and 
the appropriate regulations of relevant national regulations and the Declaration of Helsinki 
(revised version of Edinburgh, Scotland, October 2000).

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APPENDIX A - STUDY SCHEDULE 
Visit 
VS1 a 
VA1 a 
VA2 b 
VA3 c 
VA4 
VA5 
VA6 
VA7 
Visit Window 
Screening (Day 
-14 to 0) 
Day 0 
1 month (±3 
Days) 
3 months 
(±14 Days) 
 6 months (± 
30 Days) 
 12 months (+ 
30 Days) 
24 months (± 
3 Months) 
36 months (± 3 
Months) 
Informed Consent 
X 
 
 
 
 
 
X 
 
Eligibility Criteria 
X 
 
 
 
 
 
 
 
Eligibility Criteria Check 
 
X 
 
 
 
 
X 
 
Randomization 
 
X 
 
 
 
 
 
 
Injection Treatment (Allograft or 
Saline)  
 
X 
 
 
 
 
Xf 
 
Demographic Data 
X 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
Physical Examination 
 
X 
X 
X 
X 
X 
Xf 
 
Neurological Examination 
 
X 
X 
X 
X 
X 
X f 
 
MRI and X-ray Evaluations 
X 
 
X 
X d 
X e 
X 
Xf 
 
Laboratory Investigation 
X 
 
X 
X 
X 
X 
Xf 
 
Urine/Pregnancy Test, if applicable 
 
X 
 
 
 
 
 
 
VASPI Questionnaire 
X 
 
X 
X 
X 
X 
X 
X 
SF-36 Questionnaire 
X 
 
X 
X 
X 
X 
X 
X 
ODI Questionnaire 
X 
 
X 
X 
X 
X 
X 
X 
Resource Utilization 
X 
 
 
 
X 
X 
X 
X 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
a VS1 and VA1 may both occur on Day 0. 
b Month 1 Visit (VA2*) to be performed for the first 24 subjects randomized only. 

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c Subjects randomized to conservative care will be evaluated at 3 months to assure they are not experiencing further debilitating changes. During this visit, 
subjects may be offered crossover to allograft treatment. To administer the crossover allograft treatment, a new visit will be scheduled and this visit will be 
considered as the new Active Phase Day 0 (VA1). 
d MRI and X-ray to be done in the event a subject crosses over from conservative care to the Allograft treatment. 
e At the 6-month follow-up visit, subjects will be randomized to receive a MRI, (1:1 ratio). Crossover subjects to allograft treatment will all receive an MRI at the 6 
month visit after allograft treatment. All subjects will receive an X-ray at the 6 month follow up visit. 
f At the 24-month in-office visit, subjects will first be reevaluated for inclusion/exclusion and fill out VASPI, ODI, SF-36, and Resource Utilization. If eligible for 
allograft treatment, the PI will perform a neurological exam, physical exam, laboratory investigation, and MRI/X-ray. 
 
 
 
 
 
 

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APPENDIX B– Supplemental TRANSPLANTATION /OTHER APPENDICES 
12.3 
Used Scores and Scales 
 
12.3.1 Oswestry Low Back Pain Disability Questionnaire modified according to Hudson-
Cook (OPDQ) and calculated as the Oswestry Disability Index (ODI) 
 
12.3.2 VAS (pain) 
 
12.3.3 SF-36, (United States) version 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX C – Supplemental TRANSPLANTATION 
Cell 
Solution
Micronized 
Nuclei 
Pulposi
Via Disc
FINAL PRODUCT PREPARATION
P R O D U C T  C O N F I G U R AT I O N
o Cells are suspended in 1 mL of Cryoprotectant
o Reconstitute with 1 mL of Normal Saline
o Add to 0.75 cc Micronized NP
o Inject with 22 g spine needle
CONFIDENTIAL, NOT FOR DISTRIBUTION  |  VIVEX BIOMEDICAL  © 2017
 
 
 
 
 

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REFERENCE LIST 
1 World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research 
involving human subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended 
by the 29th WMA General Assembly, Tokyo, Japan, October 1975 35th WMA General Assembly, Venice, Italy, 
October 1983 41st WMA General Assembly, Hong Kong, September 1989 48th WMA General Assembly, Somerset 
West, Republic of South Africa, October 1996 and the 52nd WMA General Assembly, Edinburgh, Scotland, October 
2000. Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002. Note of 
Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004. 
2 Kelsey, J.; White, A. A.: Epidemiology and impact of low back pain. Spine 6 (1980) 133 - 142 
3 Waddell, G.: A new clinical model for the treatment of low back pain. Spine 12 (1987) 632 - 644 
4 Nachemson, A.: Recent advances in the treatment of low back pain. Int Orthop 9 (1985) 1 – 10 
5 Kopec J. A.; Esdaile J. M.; Abrahamowicz M.; Abenhaim L.; Wood-Dauphinee S., Lamping D. L., Willianms J. I.: The 
Quebec Back Pain Disability Scale: Conceptualization and Development. J Clin Epidemiol 49 (1996) 151 - 161 
6 Kraemer, J.: Bandscheibenbedingte Erkrankungen. 4. Aufl. Stuttgart – New York: G. Thieme 1997 
7 Mac Iniosh, J. E.; Bogduk, N.: The morphology of the lumbar erector spinae. Spine 12 (1987) 658 – 668 
8 Parke, W. W.; Watanabe, R.: Lumbosacral intersegmental epispinal axons and ectopic ventral nerve rootlets. J 
Neurosurg 67 (1987) 269 - 277 
9 Rydevik, R.; Brown M. D.; Lundborg, G.: Pathoanatomy and Pathophysiology of nerve root compression. Spine 9 
(1984) 7 – 15 
10 Watanabe, R.; Parke, W. W.: Vascular and neural pathology of lumbosacral spinal stenosis. J Neurosurg 64 (1986) 64 
– 70 
11 Buttner-Janz, K.: The Development of the Artificial Disc SB Charite. Dallas, Hundley & Associates (1992) 
12 Buttner-Janz, K.; Schellnack K.; Zippel, H.: Biomechanics of the SB Charite lumbar intervertebral disc endoprothesis. 
Int Orthop (1989) 173 – 176 
13 Griffith S. L.; Shelokov, A. P.; Buttner-Janz, K.; et al: A multicenter retrospective study of the clinical results of the 
LINK SB Charite intervertebral prosthesis: The initial European experience. Spine 19 (1994) 1842 – 1849 
14 Lemaire J. P.; Skalli, W.; Lavaste F.; et al: Intervertebral disc prosthesis: Results and prospects for the year 2000. Clin 
Orthop 337 (1997) 64 – 76 
15 Ray C. D.: The artificial disc. In Weinstein J. N. (ed): Clinical efficacy and outcome in the diagnosis and treatment of 
low back pain. New York, Raven Press (1992) 205 – 226 
16 Schoenmayr R.; Lotz C.; Lotz-Metz G.; et al: The implantation of a hydrogel disc nucleus prosthesis in the 
degenerative lumbar disc disease: Early experiences with 10 patients. Proceedings of the International Intradiscal 
Therapy Society, 10th Annual Meeting, Naples, FL (1997) 
17 Zeegers W. S.; Bohnen L. M.; Laaper M.; et al: Artificial disc replacement with the modular type SB Charite III: 2-
year results in 50 prospectively studied patients. Eur Spine 8 (1999) 210 – 217 
18 Kusior L. J.; Vacanti C. A.; Bayley J. C.; et al: Tissue engineering of nucleus pulposus in nude mice. Trans Orthop 
Res Soc 24 (1999) 807 
19 Nishida K.; Kang J. D.; Gilbertson L. G.; et al: Modulation of the biologic activity of the rabbit intervertebral disc by 
gene therapy: An in vivo study of adenovirus-mediated transfer of the human transforming growth factor ß1 
encoding gene. Spine 24 (1999) 2419 – 2425 
20 Takegami K.; Masuda K.; Kumano F; et al: Osteogenic protein-1 is most effective in stimulating nucleus pulposus and 
annulus fibrosus cells to repair their matrix after chrondroitinase ABC-induced chemonucleosis. Trans Orthop Res 
Soc 24 (1999) 201 
21 Grifka, J.; Anders, S.; Löhnert, J.; Baag, R.; Feldt, S.; Regeneration von Gelenk-knorpel durch die autologe 
Chondrozytentransplantation. Arthroskopie 13, (2000) 113 – 122 
22 Brittberg, M.; Lindahl, A.; Nilsson A.; Ohlsson, C.; Isaksson, O.; Peterson, L.: Treatment of deep cartilage defects in 
the knee with autologous chondrocyte transplantation. N Engl J  Med 331 (1994) 889 -  895 
 

CONFIDENTIAL 
Clinical Protocol  
DATE 
9Dec2019 
Page  
 TITLE:  Viable Allograft Supplemented Disc Regeneration in the Treatment of 
Patients with Low Back Pain with or without Intervertebral Disc Herniation – 
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WRITER      
TG, DB, PW   
NO. 
61 
REV 
6 
 
61 
 
 
23 Strem BM, Hicok KC, Zhu M, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 
2005; 54:132-141 
24 Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies 
2001: 7:211-228 
25 Case J, Horvath TL, Howell JC, et al. Clonal multilineage differentiation of murine common pluripotent stem cells 
isolated from skeletal muscle and adipose stromal cells. Ann NY Acad Sci  2005; 1044:183-200 
26 Moon S. H.; Nishida K.; Kang J. D.; et al: Human intervertebral disc cells are susceptible to adenovirus-mediated gene 
transfer. Proceedings of the 14th Annual Meeting of the North Amercian Spine Society, Chicago (1992) 92 – 94 
27 Thompson J. P.; Oegema T. R. Jr.; Bradford DS: Stimulation of mature canine intervertebral disc by growth factors. 
Spine 16 (1991) 253 – 260 
28 Josimovic-Alasevic, O.; Meisel, H. J.; Prosenc, N.; Fritsch, K. G.; Siodla, V.; Brock, M.: Three dimensonal cultures of 
cells derived from fibrous disc cartilage for treatment of discopathy. Cartilage Repair (1997) 97 
29 Chelberg, M. K.; Banks G. M.; Geiger, D. F.; Oegema T. R. Jr.: Identification of heterogenous cell populations in 
normal human intervertebral disc. J Anat 186 (1995) 43 – 53 
30 Okuma M.; Mochida, J.; Nishimura, K.; Sakabe, K.; Seiki, K.: Reinsertion of stimulated nucleus pulposus cells retards 
intervertebral disc degeneration: an in vitro and in vivo experimental study. J Orthop Res 18 (2000) 988 – 997 
31 Ganey TM, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC. Disc Chondrocyte Transplantation in a 
Canine Model: A Treatment for Degenerated or Damaged Intervertebral Disc. Spine 28:2609-2620, 2003 
31 Meisel, H. J. et al. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for 
degenerated or damaged intervertebral disc. Biomol.Eng, 24. 5. 2007 
32 Use of ADRCs for Repairing the Intervertebral Disc following Partial Discectomy in Dogs (report on file at Cytori , 
SRT07-153, Rev A) 
33 Brock, M.; Görge, H. H.; Curio, G.: Intradiscal pressure-volume response: a methodological contribution to 
chemonucleolysis. J Neurosurg 60 (1984) 1029 – 1032 
34 Olson, E. J.; Hanley E. N. Jr.; Rudert M. J.; et al: Vertebral column allografts for the treatment of segmental spine 
defects: An experimental investigation in dogs. Spine 16 (1991) 1081 – 1088 
35 Diwan A. D.; Parvataneni H. K.; Khan S. N.; Sandhu H. S.; Girardi F. P.; Cammisa F. P.: Current Concepts in 
intervertebral disk restoration. Tissue Engineering in Orthopedic Surgery. Orthopedic Clinics of North America J 
3 (2000) 453 – 464 
36 Hudson-Cook N.; Tomes-Nicholson K.; Breen A: A revised Oswestry Disability Questionnaire. Back Pain: New 
approaches to rehabilitation and education (1989) 187 – 204 
37 SF-36 Standard German Version 1.0, IQOLA, copyrights 1994 
38 Prolo D. J.; Oklund S. A., Butcher M.: Towards uniformitiy in evaluating results of lumbar spine operations. Spine 11 
(1986) 601 – 606 
39 VAPS Visual Analogue Pain Scale aus: Huskisson E. C.: Measurement of pain. The Lancet 4 (1974) 1127 – 1131 
40  
Modic M. T.; Steinberg P. M.; Ross J. S.; et al: Degenerative disk disease: Assessment of changes in vertebral 
body marrow with MR imaging. Radiology 166 (1988) 193 – 199 
41 Ross, J. S.; Zepp, R.; Modic, M. T.: The postoperative lumbar spine: Enhanced MR evaluation of the intervertebral 
disc. American Soc of Neuroradiology 17 (1996) 323 –331 
42 Mochida J.; Nomura T.; Toh E.; Chiba M.: The importance of  preserving disc structure in surgical approaches to 
lumbar disc herniation. Spine 21 (1996) 1556 – 1563 
43 Kitamura K, Mori M, Sugimachi K. Stem cell augmented reconstruction: a new hope for reconstruction after breast 
conservation therapy. San Antonio Breast Cancer Symposium (SABCS); 30th Annual Meeting Dec 13 – 16, 2007, 
San Antonio, TX Poster Presentation 
44 Rigotti, G., Marchi, A., Gallie, M., Baroni, G., Benati, D. and Sbarbati, A. “Therapeutic Angiogenesis for Ischemic 
Tissue by Autologous Transplantation of Adipose-Derived Adult Stem Cells.” International Fat Applied 
Technology Society (IFATS); Third Annual Meeting Sept 10 – 13, 2005, Charlottesville VA, p.13 
45 Kitamura et al., Stem cell augmented reconstruction: A new hope for reconstruction after breast conservation therapy. 
Abstract submitted to 2007 San Antonio Breast Cancer Symposium 

CONFIDENTIAL 
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WRITER      
TG, DB, PW   
NO. 
62 
REV 
6 
 
62 
 
 
46 Yoshimura K, Matsumoto D, and Gonda K..  “A Clinical Trial of Soft-Tissue Augmentation by Lipoinjection with 
Adipose-Derived Stromal Cells (ASCs).”  International Fat Applied Technology Society (IFATS); Third Annual 
Meeting Sept 10 – 13, 2005, Charlottesville VA, p.9. 
47 Rigotti G, Marchi A, Gallie M, Baroni G, Benati D and Sbarbati A. “Therapeutic Angiogenesis for Ischemic Tissue by 
Autologous Transplantation of Adipose-Derived Adult Stem Cells.” International Fat Applied Technology Society 
(IFATS); Third Annual Meeting Sept 10 – 13, 2005, Charlottesville VA, p.13. 
48 Kamakura, T. 94th Bi-Annual Congress of the Japan Society of Aesthetic Surgery, May 2008. 
49 APOLLO-01 www.clinicaltrials.gov Protocol #NCT00442806 
50 PRECISE-01 www.clinicaltrials.gov Protocol #NCT00426868 
51 Fairbank JC.; Pynsent PB.: The Oswestry Disability Index. Spine 25 (2000) 2940 - 2953 
52 Fritz JM.; Irrgang JJ.: A Comparison of a Modified Oswestry Low Back Pain Disability Questionnaire and the Quebec 
Back Pain Disability Scale. Phys Ther 81 (2001) 776 – 788