Clinical Outcomes Associated With the Use of ViviGen® in Conjunction With Posterolateral Fusion for the Treatment of Lumbar Degenerative Disc Disease
Phase: NA
Conditions: Lumbar Spondylolisthesis, Degenerative Disc Disease, Degenerative Spondylolisthesis, Lumbar Radiculopathy, Lumbar Spinal Stenosis, Lumbar Disc Disease
Sponsor: Corewell Health East

TITLE:  
Clinical Outcomes Associated With the Use of ViviGen® for the 
Treatment of Lumbar Degenerative Disc Disease 
NCT03733626 
 
Approval date: 10/18/2019 
 
Study Protocol and Statistical Analysis Plan 

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Clinical Outcomes Associated with the use of ViviGen® in 
Conjunction with Posterolateral Fusion for the Treatment of 
Lumbar Degenerative Disc Disease 
Jad G. Khalil, M.D. (First Author)
Department of Orthopaedic Surgery
William Beaumont Hospital
3535 West 13 Mile Rd., Suite 744
Royal Oak, MI  48073
jadkhalil@gmail.com
Jeffrey S. Fischgrund, M.D. 
Department of Orthopaedic Surgery
William Beaumont Hospital
3535 West 13 Mile Rd., Suite 744
Royal Oak, MI  48073
jsfischgrund37@gmail.com
Kevin C. Baker, Ph.D.* (Corresponding Author)
Department of Orthopaedic Surgery
William Beaumont Hospital
3535 West 13 Mile Rd., Suite 744
Royal Oak, MI  48073
Kevin.Baker@beaumont.org
Richard V. Roberts, M.D.
Department of Orthopaedic Surgery
William Beaumont Hospital
3535 West 13 Mile Rd., Suite 744
Royal Oak, MI  48073
richardrobertsmd@gmail.com
*For Correspondence:
Kevin C. Baker, Ph.D.   Director, Orthopaedic Research Laboratory
Department of Orthopaedic Surgery   3811 West 13 Mile Rd., Suite 404   Royal Oak, MI  48073
Office: (248) 551-9726   Fax:  (248) 551-0191  Kevin.baker@beaumont.edu
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Introduction 
DePuy Synthes, Inc. is proposing a prospective randomized interventional outcomes study of 
clinical safety and fusion rates in subjects who have received standard-of-care one or two-level 
posterolateral lumbar fusion surgery with instrumentation using ViviGen® Cellular Bone Matrix 
on-label for the treatment of degenerative disc disease. 
Background and Significance
Nearly half of the estimated 500,000 bone grafting procedures performed annually in the United 
States involve spine fusion.1 Traditionally, autologous bone grafts are used to repair damaged 
bone caused by trauma, infection, malignancy, degenerative disease and congenital deformity. 
However, harvesting of bone autograft is an invasive procedure that can lead to significant donor 
site morbidity.2 
Bone graft substitute (BGS) materials offer an alternative to autograft bone capable of supporting 
new bone growth, while avoiding or minimizing the frequent co-morbidities associated with 
autograft harvest from the iliac crest.3-5 Allograft bone has been used successfully for more than 
two decades as a first-generation alternative to autograft bone. While traditional processed 
allograft bone can be difficult to shape, shows variable resorption characteristics, and variable 
biological activity, ViviGen® Cellular Bone Matrix has addressed these issues in their product. 
While containing all the properties required for bone formation, it additionally has a consistency 
that allows it to hold shape in a putty-like consistency.6 ViviGen® Cellular Bone Matrix can be 
molded into a specific form that allows proper placement, positioning and formation during 
posterolateral lumbar fusion.6  
Description of ViviGen®6
ViviGen® is manufactured by DePuy Synthes, Inc. (West Chester, Pennsylvania). ViviGen® 
Cellular Bone Matrix is comprised of cryopreserved viable cortical cancellous bone matrix and 
demineralized bone. ViviGen® Cellular Bone Matrix is a Human Cells, Tissues, and Cellular 
and Tissue-based Product (HCT/P) as defined by the U.S. Food and Drug Administration in 21 
CFR 1271.3. ViviGen® Cellular Bone Matrix is processed from donated human tissue, resulting 
from the generous gift of an individual or his/her family. 
ViviGen® Cellular Bone Matrix contains all of the properties required for bone formation being 
that it is osteoconductive, osteoinductive and osteogenic. Safety of ViviGen® Cellular Bone 
Matrix is defined by every lot is aseptically processed and final product is tested for sterility 
using USP standards. Packaging and handling is beneficial in that all four sizes of ViviGen® 
Cellular Bone Matrix will thaw in less than 5 minutes, which is vital for cell viability, in that the 
ported pouch allows for the quick and efficient removal of the cryopreservation media and 
rinsing solutions. ViviGen® Cellular Bone Matrix maximizes cell viability by modes of 
processing that is focused on protecting viable lineage committed bone cells from recovery to 
implantation. 
Objective
The objective of this study is to perform a prospective, randomized, controlled clinical trial to 
compare radiographic fusion rates and patient reported outcomes, including pain and function 
preoperatively and postoperatively, using Depuy ViviGen® Cellular Bone Matrix mixed with 
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cortical/cancellous allograft in conjunction with an approved Depuy Synthes pedicle screw 
system compared to autograft mixed with cortical/cancellous allograft in conjunction with the 
same DePuy Synthes pedicle screw system used for a one or two- level posterolateral lumbar 
fusion.
Methodology
Study Design
This is a prospective randomized, non-blinded, controlled study.  Patients with a 
diagnosis of degenerative disc disease and/or up to grade I spondylolisthesis and planning to 
undergo a 1- or 2-level instrumented posterolateral lumbar fusion surgery between L1-S1 will be 
screened.  If eligible and the subject meets all the inclusion criteria and none of the exclusion 
criteria, the subject will be approached about study participation by the surgeon.  If the subject 
agrees to participate, the consent process will be initiated by the study coordinator. Once the 
patient has been consented; data including medical history, neurological exam, patient 
questionnaires (VAS, ODI, SF-36) will be collected.  Randomization will occur once a surgery 
date has been scheduled so the appropriate instrumentation can be boarded accordingly.  A 
randomization envelope will reveal randomization treatment group.  The envelopes will be 
generated in a 1:1 fashion and be randomly allocated to an assigned study identification number.
Subjects will be randomized to either:  1) treatment arm where the investigator will use an FDA 
approved/cleared DePuy Synthes spinal pedicle screw system with ViviGen® Cellular Bone 
Matrix mixed with cortical/cancellous allograft or the 2) control arm where the investigator use 
the same DePuy Synthes spinal pedicle screw system with local autologous bone graft mixed 
with cortical/cancellous allograft.   Both treatment groups represent standard of care lumbar 
fusion surgeries using two types of bone graft options to create the arthrodesis as comparators. 
Once the lumbar fusion surgery has taken place as planned; data will be collected 
regarding the surgery performed, including operative time, amount of bone graft used, spinal 
system used, length of hospital stay, and adverse events/complications.
Study subjects will be followed up at 6-weeks, 3-months, 6-months, and 12-months 
postoperatively at the private practice or clinic. During these routine (standard of care) 
postoperative visits, subjects will complete questionnaires (VAS, ODI, SF-36, patient 
satisfaction) and have neurological exam (lumbar spine exam, see appendix 1) completed by the 
investigator.  Adverse events related to device and/or procedure will be evaluated as each 
postoperative visit.  AP and lateral x-rays will be performed at all visits with flexion and 
extension x-rays added at baseline, 3-months, 6-months, and 12-months.  A CT scan of the 
lumbar spine will be performed during the 12-month postoperative time frame at the Beaumont-
RO Imaging Center.   Radiographic analysis will be performed and evaluated for fusion status as 
evidenced by bony bridging, presence of radiolucency, and development of pseudoarthrosis at 
each follow-up visit. 
This study design reflects the current standard of care for lumbar spinal stenosis, 
degenerative disc disease and lumbar degenerative spondylolisthesis.  Lumbar fusion surgery 
using pedicle screw fixation with autograft and allograft bone grafting options is treatment of 
choice after conservative (non-surgical) therapies have been implemented and failed.
Statistical Analysis
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The sample size will consist of 40 patients; 20 in each treatment arm.  The 
primary hypothesis is that the probability of achieving fusion using ViviGen bone graft is not 
clinically inferior to using autograft and allograft in lumbar fusion at 12-months post-surgery.  
Using a one-sided test and fusion rate of 86%, there is a 0.80 probability of 0.80 of finding a 
difference for 60 patients.  A 10% dropout rate was considered.  Forty patients may result in low 
statistical power; however, this may be increased by 10 in each arm once enrollment has 
obtained and if needed, and upon agreement with study sponsor.  Enrollment of 40 reflects the 
current allotted grant/budget per the study sponsor for this project. 
There are other studies that analyzed demineralized bone matrix in two-year fusion 
outcomes for lumbar spinal fusions that used a similar size population (range between 13 and 28 
patients) to the proposed enrollment for this study, as demonstrated in Vaccaro et al (2007) and 
Kang et al (2012).  Power calculation for the primary outcome of bone fusion was obtained using 
PASS 15.  An 86% fusion rate (Kang et al) was assumed with a 10% dropout rate for both arms.  
Secondary endpoints (VAS, ODI, SF-36, neurological status, and fusion) will be 
quantified to detect changes longitudinally from baseline through 12-months post-surgery.
Study Population and Inclusion/Exclusion Criteria
Patients with a diagnosis of spinal stenosis, degenerative disc disease and/or up to 
grade I spondylolisthesis and planning to undergo a 1or 2-level instrumented posterolateral 
lumbar fusion surgery between L1-S1 will be asked to participate in the study.  If eligible, the 
consent process will be initiated by the study coordinator
A subject may be included if the following criteria are met:
1. ≥18 years of age
2. Able to provide consent
3. Is undergoing standard of care one or two-level instrumented posterolateral fusion 
at the level between L1-S1
4. Has diagnosis of spinal stenosis, degenerative disc disease and/or up to Grade 1 
spondylolisthesis
5. Requires decompression at intended fusion level (multi-level decompression 
allowed L1-S1)
6. Has failed 6-weeks or more of conservative, non-operative treatment 
7. Has back and/or radicular lumbar symptoms with ODI (Oswestry Disability 
Index) score of ≥ 30 preoperatively.
A subject will be excluded if any of the following criteria are met:
1. Any prior lumbar fusion surgery
2. Requires fusion of more than two levels 
3. Requires an interbody fusion based on relevant diagnosis and factors (such as 
foraminal stenosis, degree of spondylolisthesis, spinal deformity, disc space 
collapse, and subject’s age) as determined by investigator
4. BMI > 40
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5. Active systemic infection or infection at operative site
6. History of an osteoporotic fracture and/or vertebral body fracture
7. Is currently being treated with chemotherapy, radiation, immunosuppression or 
chronic steroid therapy
8. History of osteoporosis, osteopenia, or osteomalacia that would contraindicate 
spinal surgery
9. Psychological or physical condition in the opinion of the investigator that would 
interfere with subject self-assessments
10. History of neurological condition in the opinion of the investigator that may affect 
lumbar function and pain assessments
11. Subjects with a history of cancer must be disease free for at least 3 years
12. Pregnant, or plans on becoming pregnant
Intervention
Treatment arm/group: 20 subjects undergoing open, one or two-level instrumented posterolateral 
lumbar fusion surgery using ViviGen Cellular Bone Matrix mixed with cortical/cancellous 
allograft and DePuy Synthes pedicle screw system.
Control arm/group: 20 subjects undergoing open, one or two-level posterolateral lumbar fusion 
surgery using local autograft mixed with cortical/cancellous allograft and DePuy Synthes pedicle 
screw system.
Data and Safety Monitoring
The PI and study team (including sub-investigators, clinical research manager) will be 
responsible for data and safety monitoring.  All adverse events will be reviewed to 
determine relatedness to the product and reported to sponsor as necessary (if related to product 
and unanticipated according to risk profile).  The data will be reviewed for maintenance of 
confidentiality and integrity as well as the data collection process.  The data and safety review 
will take place every six months from the date of the first patient enrolled into the study or after 
every ten patients enrolled whichever comes first.
Adverse Events
Relevant adverse events (those related to the study device, the surgical procedure, or the lumbar 
spine) will be recorded in this study. All adverse events will be reviewed for relatedness and 
expectedness by the PI on a case by case basis and per Data and Safety Monitoring guidelines.  
Protocol Deviations
The investigators are responsible for documenting all protocol deviations, including an 
explanation for why the deviation occurred.  All protocol deviations will be recorded and 
submitted to the IRB per policy.
Outcomes
Primary Endpoint
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
Successful lumbar fusion as measured by CT scan and flexion/extension 
x-rays at 12-months; as evidenced by bony bridging, presence of 
radiolucency, no development of pseudoarthrosis
Secondary Endpoints

Improvement in patient reported outcomes as measured by VAS (≥ 2-point 
improvement), ODI (≥ 15-point improvement), SF-36 (≥ 15-point 
improvement) from baseline to 12-months. 

No new or worsening neurological (motor and sensory) deficit as compared to 
baseline through 12-months. No revision surgery and/or development of 
pseudoarthrosis by month 12.

No occurrence of adverse events related to device by month 12.
Subject Screening and Enrollment
Patients who have already planned a decompressive lumbar laminectomy and fusion surgery will 
be approached about potential study participation.  If the patient wishes to proceed with study 
participation, the study coordinator will go through the informed consent process.  After the 
consent process has been completed, the subject will be further screened for eligibility and given 
the subject questionnaires to complete.  
Screen Failures
If the subject does not meet all inclusion criteria or meets one of the exclusion criteria after 
signing consent, then the subject will be considered a screen failure and therefore, not enrolled 
into the study.  The subject will also be considered a screen failure and not enrolled in the study 
if there is a change in surgical treatment based on the surgeon’s observations and best practice 
intraoperatively.  
Withdrawals
A subject who withdraws consent prior to study completion will be removed from the study and 
no longer followed.  The surgery, instrumentation, and bone grafts are FDA approved and 
cleared and considered standard of care.  The subjects may follow-up as needed and per standard 
of care at their own discretion if they decide to no longer participate in the study. 
The reasons for voluntary withdrawal or discontinuation of study subjects will be documented. If 
during the course of the clinical study, a study subject is non-responsive to attempts to schedule 
follow-up visits, communication methods such as phone calls, emails, mail, or other means as 
appropriate in an attempt schedule an appointment or determine if the subject has moved, died, 
or otherwise become lost to follow-up. 
Summary and Rationale of Proposed Study 
The purpose of this study is to collect on-label safety and efficacy data where ViviGen® Cellular 
Bone Matrix is applied to posterolateral lumbar fusion with DePuy Synthes pedicle screw 
system.  It is expected that this study will contribute to the compilation of clinical data required 
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to demonstrate the ability of ViviGen® Cellular Bone Matrix to promote safe, effective and 
timely spine fusion in patients who undergo posterolateral lumbar fusion surgery. The results of 
this study will lead to further analysis (i.e. comparison to historical data of other marketed bone 
graft products, as well as, to local bone alone). 
References
1. Boden SD. Overview of the biology of lumbar spine fusion and principles for selecting a bone        
graft substitute. Spine 27, S26-S31 (2002). 
2. Kim, D et al. Prospective study of iliac crest bone graft harvest site pain and morbidity. Spine 
9, 886-892 (2009). 
3. Betz, R. Limitations of autograft and allograft: new synthetic solutions. Orthopedics 25, s561-
s570 (2002). 
4. Gazdag, A; Lane, J; Glaser, D; Forster, R. Alternatives to autogenous bone graft: efficacy and 
indications. J Am.Acad.Orthop.Surg. 3, 1-8 (1995). 
5. DeCoster, T; Gehlert, R; Mikola, E; Pirela-Cruz, M. Management of post-traumatic segmental 
bone defects. J Am.Acad.Orthop.Surg. 12, 28-38 (2004).
6. DePuy Synthes. https://www.depuysynthes.com/hcp/spine/products/qs/vivigen-cellular-bone-
matrix. Copyright DePuy Synthes 2014-2017. DePuy Synthes Biomaterials Division 1302 
Wrights Lane East, West Chester, Pennsylvania 19380.
7. Vaccaro AR, Stubbs HA, Block JE. Demineralized bone matrix composite grafting for 
posterolateral spinal fusion. Orthopedics. 2007 Jul; 30(7): 567-70. 
8. Kang J, An H, Hilibrand A, Yoon ST, Kavanagh E, Boden S. Grafton and local bone have 
comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine. 2012 
May 20;37(12):1083-91.
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Study Synopsis
Sponsor
DePuy Synthes
Protocol Version
Version 1.5 Date 06.04.2018
Study Title
Clinical Outcomes Associated with the use of ViviGen® in Conjunction with 
Posterolateral Fusion for the Treatment of Lumbar Degenerative Disc Disease
Site
Beaumont Health – Royal Oak  (William Beaumont Hospital)
Study Design
Prospective, randomized, interventional outcomes study
Study Duration
Approximately 4 years (enrollment of first subject to the last follow-up visit)
Enrollment Number
 Total: 40                 20 – ViviGen treatment arm
                                 20 – Control arm
                                 
Treatment Arm
20 subjects undergoing one or two-level instrumented posterolateral lumbar 
fusion surgery using ViviGen Cellular Bone Matrix mixed with 
cortical/cancellous allograft and DePuy Synthes pedicle screw system
Control Arm
20 subjects undergoing open, one or two-level posterolateral lumbar fusion 
surgery using local autograft mixed with cortical/cancellous allograft and 
Depuy Synthes pedicle screw system. 
Study Objectives

Primary Objective:
1.
To evaluate bone fusion using ViviGen Cellular Bone Matrix 
for one or two-level instrumented posterolateral lumbar fusion 
surgery

Secondary Objectives:
1.
To evaluate VAS, ODI, SF-36 and patient satisfaction scores 
postoperatively compared to baseline/preoperative.
2.
Evaluate the occurrence of procedure and/or device related 
adverse events
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Study Endpoints
Primary Endpoint:

Successful lumbar bone fusion as measured by CT scan and 
flexion/extension x-rays at 12-months; as evidenced by bony bridging, 
presence of radiolucency, no development of pseudoarthrosis
Secondary Endpoints:

Improvement in patient reported outcomes as measured by VAS (≥ 2-
point improvement), ODI (≥ 15-point improvement), SF-36 (≥ 15 point 
improvement) from baseline to 12-months. 

No new or worsening neurological (motor and sensory) deficit as 
compared to baseline through 12-months. No revision surgery and/or 
development of pseudoarthrosis by month 12.

No occurrence of adverse events related to device by month 12.
Inclusion Criteria
A subject may be included if the following criteria are met:
1.
≥18 years of age
2.
Able to provide consent
3.
Is undergoing standard of care one or two-level instrumented 
posterolateral fusion at the level between L1-S1
4.
Has diagnosis of spinal stenosis, degenerative disc disease 
and/or up to Grade 1 spondylolisthesis
5.
Requires decompression at intended fusion level (multi-level 
decompression allowed L1-S1)
6.
Has failed 6-weeks or more of conservative, non-operative 
treatment 
7.
Has back and/or radicular lumbar symptoms with ODI 
(Oswestry Disability Index) score of ≥ 30 preoperatively.
Exclusion Criteria
A subject will be excluded if any of the following criteria are met:
1.
Any prior lumbar fusion surgery
2.
Requires fusion of more than two levels
3.Requires an interbody fusion based on relevant diagnoses and 
factors (such as foraminal stenosis, degree of 
spondylolisthesis, spinal deformity, disc space collapse, and 
subject’s age) as determined by investigator
3.
BMI > 40
4.
Active systemic infection or infection at operative site
5.
History of an osteoporotic fracture and/or vertebral body 
fracture
6.
Is currently being treated with chemotherapy, radiation, 
immunosuppression or chronic steroid therapy
7.
History of osteoporosis, osteopenia, or osteomalacia that would 
contraindicate spinal surgery
8.
Psychological or physical condition in the opinion of the 
investigator that would interfere with subject self-assessments
9.
History of neurological condition in the opinion of the 
investigator that may affect lumbar function and pain 
assessments
10. Subjects with a history of cancer must be disease free for at 
least 3 years
11. Pregnant, or plans on becoming pregnant
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Study Summary
All subjects who sign an IRB approved consent form are considered in active 
screening to determine eligibility.  Once a subject is consented, the following 
visits will take place:
Baseline (≤ 60 days of surgery):  

Medical history

Neurological exam (Lumbar Spine Exam, appendix 1)

Demographics

VAS, ODI, SF-36 questionnaires

Lumbar spine x-rays AP/lateral, flexion/extension or as done per 
standard of care

Randomization
Surgical Visit:

Surgery performed

Operative Time

Amount of Bone Graft used 

Pedicle Screw System used

Length of Hospital Stay

Adverse Events/Complications
6-week Visit (± 2 weeks):

VAS, ODI, SF-36, patient satisfaction questionnaires

Neurological Exam

Lumbar AP/Lateral x-rays

Adverse Events
3-month Visit (± 3 weeks):

VAS, ODI, SF-36, patient satisfaction questionnaires

Neurological Exam

Lumbar AP/Lateral and flexion/extension x-rays

Adverse Events
6-month Visit (± 1 month):

VAS, ODI, SF-36, patient satisfaction questionnaires

Neurological Exam

Lumbar AP/Lateral and flexion/extension x-rays

Adverse Events
12-month Visit (± 2 months):

VAS, ODI, SF-36, patient satisfaction questionnaires

Neurological Exam

Lumbar AP/Lateral and flexion/extension x-rays

CT scan of the lumbar spine without contrast

Evaluate fusion status

Adverse Events
IRB NUMBER: 2018-158
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