Stimgenics Open-Label, Post Market Study: A Clinical Trial to Study the Effects of Stimgenics Spinal Cord Stimulation (SGX-SCS) Programs in Treating Intractable Chronic Back Pain
Phase: NA
Conditions: Chronic Low Back Pain
Sponsor: Stimgenics LLC

 
Stimgenics SGEN-2018PM2 Rev 2.0 
 
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CLINICAL INVESTIGATIONAL PLAN 
Stimgenics Open-Label, Post Market Study: A Clinical Trial to Study the Effects of Stimgenics 
Spinal Cord Stimulation (SGX-SCS) programs in treating Intractable Chronic Back Pain 
Protocol Number: 
 
 
SGEN-2018PM2 
NCT Number  
 
 
NCT03606187 
 
Study Reference: 
 
 
SGX-SCS RCT 
 
Sponsor: 
 
 
 
Stimgenics 
2406 E. Empire St. 
Bloomington, IL 61704 
 
Study Responsibility:  
 
Wesley Park 
 
 
 
 
 
Vice President, Clinical Affairs 
 
 
 
 
 
Stimgenics 
 
Date of Issue:  
 
 
 Jan 2, 2019 
 
Revision: 
 
 
 
2.0 
 
Revision History: 
 
 
 
 
 
 
Revision 
Description 
Date 
1.0 
Initial Release of Investigational Plan 
15 May 2018 
2.0 
Amendment of the Investigational Plan 
02 Jan 2019 

 
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Study Synopsis 
Study Title 
Stimgenics Open-Label, Post Market Study: A Clinical Trial to Study the 
Effects of Stimgenics Spinal Cord Stimulation (SGX-SCS) programs in treating 
Intractable Chronic Back Pain 
 
Protocol 
Number 
SGEN-2018PM2 
Study 
Device 
The IntellisTM neurostimulator, a Spinal Cord Stimulation (SCS) device system 
manufactured and commercialized by Medtronic (Minneapolis, MN) 
 
Study 
Purpose 
The purpose of this investigational study is to study the effects of Stimgenics 
Spinal Cord Stimulation (SGX-SCS) in subjects with chronic, intractable pain 
of the trunk with lower limb pain, including unilateral or bilateral pain 
associated with the following conditions: failed back surgery syndrome, 
intractable low back pain and leg pain. 
 
Study 
Design 
This is an open-label prospective, randomized, controlled, multi-center study 
comparing SGX-SCS programming approach to Standard SCS programming 
approach. 
 
Subjects meeting study entrance criteria will be randomized in a 1:1 ratio to one 
of two study treatment groups: 
• Test treatment group with SGX-SCS programming approach  
• Control treatment group with Standard SCS programming approach 
 
Data at follow-up visits will be compared between the two treatment groups, 
and in reference to baseline assessments collected at the beginning of the study. 
 
Study Size 
Approximately 250 subjects will be enrolled at up to 15 clinical sites in the 
United States in order to include an estimated 125 subjects to the point of 
randomization and trial phase.   
 
This would allow at least 100 subjects (approximately 50% in each treatment 
arm) to complete the 3-month endpoint. 
 
Study 
Duration 
The expected total duration of this study is approximately 28 months.   
Enrollment of subjects is expected to last 12 months.  
Subjects that have received the permanent implant will be followed up for 
approximately 8 months. This consists of Baseline assessments, up to 10 days 
of trial stimulation, and 6 months of treatment following implantation and 
activation of the device. All subjects who remain implanted at the time of Study 
Completion will be offered to return for an additional visit 12-months after 
device activation.  
 

 
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Study 
Objective 
The primary objective of this study is to evaluate the effectiveness of SGX-
SCS in reducing back pain as compared to Standard SCS for the treatment of 
intractable chronic back pain. 
Inclusion 
Criteria 
A subject must MEET ALL of the following inclusion criteria: 
1. Be a candidate for SCS system (trial and implant) per labeled indication 
(back and leg pain) 
2. Has an average back pain intensity ≥ 5.0 cm on the 10.0 cm Visual Analog 
Scale (VAS) at the time of enrollment with moderate to severe chronic leg 
pain  
3. Be willing and capable of giving written informed consent to participate in 
this clinical study based on voluntary agreement after a thorough 
explanation of the subject’s participation has been provided. 
4. Be willing and capable of subjective evaluation, read and understand 
English-written questionnaires, and read, understand and sign the written 
inform consent in English. 
5. Be 18 years of age or older at the time of enrollment 
6. Be on a stable pain medication regime, as determined by the study 
investigator, for at least 30 days prior to enrolling in this study 
7. Be willing to not increase pain medications from baseline through the 3-
Month Visit 
8. Be willing and able to comply with study-related requirements, procedures, 
and visits 
 
Exclusion 
Criteria 
A subject must NOT MEET ANY of the following exclusion criteria: 
1. Has a medical, anatomical, and/or psychosocial condition that is 
contraindicated for commercially available IntellisTM SCS systems as 
determined by the Investigator 
2. Be concurrently participating in another clinical study 
3. Has an existing active implanted device such as a pacemaker, another SCS 
unit, peripheral nerve stimulator, and/or drug delivery pump, etc. 
4. Has a pain in other area(s) and/or medical condition requiring the regular 
use of significant pain medications that could interfere with accurate pain 
reporting, and/or confound evaluation of study endpoints, as determined by 
the Investigator 
5. Has mechanical spine instability as determined by the Investigator 
6. Has undergone, within 30 days prior to enrollment, an interventional 
procedure and/or surgery to treat back and/or leg pain, which is providing 
significant pain relief  
7. Has unresolved major issues of secondary gain (e.g., social, financial, 
legal), as determined by the investigator 
8. Be pregnant (determined by urine testing unless female subject is surgically 
sterile or post-menopausal. If female, sexually active, and childbearing age, 
subject must be willing to use a reliable form of birth control.) 
Primary 
Endpoint 
The primary efficacy endpoint is the percentage of randomized subjects who 
respond (a decrease in back pain VAS by at least 50% compared to baseline) to 
SCS therapy at 3 months (non-inferiority analysis).  Subjects who do not have a 

 
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successful Trial Phase are considered failures (non-responders) toward the 
primary endpoint. 
 
 
 
 

 
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A.  Purpose 
A.1.  Study Device 
The IntellisTM neurostimulator is a commercially available implantable component of a Spinal 
Cord Stimulation (SCS) device system manufactured by Medtronic (Minneapolis, MN). The 
system is indicated for spinal cord stimulation (SCS) as an aid in the management of chronic, 
intractable pain of the trunk and/or limbs-including unilateral or bilateral pain associated with 
conditions, including Failed Back Syndrome (FBS). It is designed to deliver electrical 
stimulation to the spinal cord using arrays of electrodes (also called leads) placed in the dorsal 
epidural space.  The study will use commercially available IntellisTM neurostimulator and 
compatible SCS system components from Medtronic in accordance to the approved FDA 
indication. Section D of this Investigational Plan provides detailed description of IntellisTM 
neurostimulator. 
 
A.2.  Purpose of the Investigation 
The purpose of this investigational study is to study the effects of Stimgenics spinal cord 
stimulation (SGX-SCS) programs in subjects with chronic, intractable pain of the trunk with 
lower limb pain, including unilateral or bilateral pain associated with the following conditions: 
failed back syndrome, intractable low back pain and leg pain. This study is a post market, open-
label, multi-center, prospective, randomized, controlled clinical trial that evaluates the 
treatment outcomes resulting from SGX-SCS programming approach and Standard SCS 
programming approach. Both programming approaches will be discussed in section B.1 of this 
Investigational Plan. 
 
This investigation is not comparing two different Spinal Cord Stimulation systems and their 
compatible device components.  Both SGX-SCS and Standard SCS programs will utilize an 
FDA-approved and commercially available SCS system (IntellisTM neurostimulator and 
compatible SCS components) as is, without any modification using approved parameters under 
approved labeling for indicated population. Outcomes will be assessed via standardized tests.  
 
A.3.  Study Size 
Approximately 250 subjects will be enrolled at up to 15 clinical sites in the United States in 
order to include an estimated 125 subjects to the point of randomization and trial phase.  This 
would allow at least 100 subjects (approximately 50% in each treatment arm) to complete the 
3-month endpoint. Sample size estimates are discussed further in section B.5.5 of this 
Investigational Plan.  
 
A.4.  Duration of the Investigation 

 
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The expected total duration of this study is approximately 28 months.  Enrollment of subjects 
is expected to last 12 months. Subjects that have received the permanent implant will be 
followed up for approximately 8 months. This consists of Baseline assessments, up to 10 days 
of trial stimulation, and 6 months of treatment following implantation and activation of the 
device. All subjects who remain implanted at the time of Study Completion will be offered to 
return for an additional visit 12-months after device activation. 
 
B.  Protocol 
B.1.  Rationale for Study 
It is estimated that about 20% percent of the population worldwide is affected by moderate to 
severe chronic pain1. Chronic pain becomes a burden to the individual as this affects a person’s 
ability to carry out many daily life activities, such as exercising, walking, driving a car, 
attending social events, or performing household chores.  In the United States, chronic pain is 
considered one of the most pervasive and intractable conditions affecting at least one third of 
the population at an estimated cost of five hundred billion dollars per year, when combining 
health-related expenditure and the cost-impact on loss of productivity and income2.  
Conventional medical management, including medication and physical therapy, is often not 
adequate for treating chronic pain. Medication therapy based on opioids may also lead to 
addiction. Extensive use of opioid medications in the United States has led to the declaration 
of an epidemic crisis3. Furthermore, surgical interventions have also failed to remediate severe 
cases of neuropathies and intractable back pain for many patients. Spinal cord stimulation 
(SCS) is a proven therapy that has been in use for about 50 years for various types of chronic 
pain. SCS is a reversible therapy that allows patients to evaluate the therapy for several days 
using an external neurostimulator (ENS) prior to receiving an implantable neurostimulator 
(INS) system4,5,6,7.  
Spinal Cord Stimulation (SCS) utilizes pulsed electric fields that are applied to the dorsal 
section of the spinal cord via electrode arrays, called leads, implanted in the epidural space.   
Standard SCS programming approach utilizes pulsed electric fields oscillating in the 40-250 
Hz frequency range although up to 1,200 Hz is approved for use. The electric field stimulates 
neurons that induce a tingling sensation (paresthesia) that is steered by the clinician and patient 
to overlay with the targeted pain location by modifying the applied electric field. The concept 
behind Standard SCS is that the paresthesia induced by the applied oscillating electric field 
masks pain signals travelling to the brain. Standard SCS programming typically involves 
giving patients a few program groups, allowing patients to select the program group that suits 
them best. Each program group contains multiple programs that deliver, for a given pulse rate, 
different stimulation parameters (e.g. pulse width, amplitude) to same or different electrodes. 
This approach has been used to create better paresthesia patterns for the given patient’s pain 
patterns or more tolerable paresthesia depending on patient’s different positions or postures.  
Historically, Standard SCS has not had high success for back pain patients due to the challenge 
of having paresthesia pattern overlap the back-pain region without causing uncomfortable 
paresthesia. Although different approaches to SCS exist, Standard SCS still remains the most 
used SCS programming approach in treating chronic back and leg pain.  

 
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Stimgenics SCS (SGX-SCS) programming approach relies less on paresthesia pattern and 
programmed stimulation parameters will be set to levels that span above the perception 
threshold, yet well below the levels that could cause uncomfortable paresthesia.  SGX-SCS 
will use only programming parameters that are currently available on the device. 
In a given program group, SGX-SCS provides programs with two different pulse rates and 
pulse widths for the goal of better pain relief.  For example, starting parameters may be a 
combination of a program with 50 Hz pulses with duration of up to 200 microseconds setting 
and a program with 300 Hz with a pulse duration of up to 200 microseconds.  This 
programming approach could result in patients experiencing less uncomfortable paresthesia 
than with the Standard SCS programming approach. This is possible because an SGX-SCS 
program group contains programs that allow subjects to access amplitudes below ones that 
could cause uncomfortable paresthesia and make more adjustments to the pulse rate.  Should 
SGX-SCS programming approach be shown to be as effective as Standard SCS programming 
approach, SGX-SCS may offer an alternative approach to SCS that will help thousands of 
chronic pain sufferers make substantial improvement in pain relief, reduction in disabilities, 
and reduce the likelihood of uncomfortable paresthesia. 
Stimgenics has completed a multicenter feasibility study (NCT03110601) in which 
SGX-SCS programming approach was evaluated during the required period for 
trialing SCS therapy. In this acute study 20 subjects were trialed with SGX-SCS and 
Standard SCS programming approaches.  In terms of back pain relief, SGX-SCS 
programming approach provided a mean of 68% pain relief and Standard SCS 
programming approach provided a mean of 43% pain relief, which translates to SGX-
SCS achieving 25% greater reduction than Standard SCS.  Notably with SGX-SCS, 
80% of subjects experienced 50% or better back pain relief, and 85% of the subjects 
preferred therapy received through SGX-SCS programming approach.  The safety 
results were in line with expectations of previous SCS studies and were mostly 
resolved within a few days with minimal interventions.  There was one serious adverse 
event, epidural abscess, which although uncommon, is well established as a potential 
risk in SCS trial and was not related to either programming approach. There were no 
unanticipated adverse events. 
For this study, the study design is a post market, open-label, prospective, randomized, 
controlled multi-center study that will again evaluate SGX-SCS programming and Standard 
SCS programming for chronic back and leg pain sufferers.  This scientifically sound study will 
provide more information on effectiveness of SGX-SCS programming approach. 
 
B.2.  Study Objectives 
The primary objective of this study is to evaluate the effectiveness of SGX-SCS in reducing 
back pain as compared to Standard SCS for the treatment of intractable chronic back pain. 
The secondary objectives of this study are to further demonstrate the effectiveness of the SGX-
SCS when compared to Standard SCS for the treatment of chronic pain of the trunk and limbs.  
This study will also include the characterization of the safety of SGX-SCS. 
 
B.3.  Selection of Study Population 

 
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B.3.1.  Study Population  
The intended study population is individuals suffering from chronic, intractable pain of the 
trunk and/or limbs associated with a number of conditions, including Failed Back 
Syndrome (FBS) and are candidates for commercially available SCS device systems.  
 
B.3.2.  Inclusion Criteria 
In order to participate in the study, a subject must MEET ALL of the following inclusion 
criteria: 
1. Be a candidate for SCS system (trial and implant) per labeled indication (back and 
leg pain) 
2. Has an average back pain intensity ≥ 5.0 cm on the 10.0 cm Visual Analog Scale 
(VAS) at the time of enrollment with moderate to severe chronic leg pain  
3. Be willing and capable of giving written informed consent to participate in this 
clinical study based on voluntary agreement after a thorough explanation of the 
subject’s participation has been provided. 
4. Be willing and capable of subjective evaluation, read and understand English-
written questionnaires, and read, understand and sign the written inform consent in 
English. 
5. Be 18 years of age or older at the time of enrollment 
6. Be on a stable pain medication regime, as determined by the study investigator, for 
at least 30 days prior to enrolling in this study 
7. Be willing to not increase pain medications from baseline through the 3-Month 
Visit 
8. Be willing and able to comply with study-related requirements, procedures, and 
visits 
 
B.3.3.  Exclusion Criteria 
In order to participate in the study, a subject must NOT MEET ANY of the following 
exclusion criteria: 
1. Has a medical, anatomical, and/or psychosocial condition that is contraindicated 
for commercially available IntellisTM SCS systems as determined by the 
Investigator 
2. Be concurrently participating in another clinical study 
3. Has an existing active implanted device such as a pacemaker, another SCS unit, 
peripheral nerve stimulator, and/or drug delivery pump, etc. 
4. Has pain in other area(s) and/or medical condition requiring the regular use of 
significant pain medications that could interfere with accurate pain reporting, study 
procedures, and/or confound evaluation of study endpoints, as determined by the 
Investigator 
5. Has mechanical spine instability as determined by the Investigator 

 
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6. Has undergone, within 30 days prior to enrollment, an interventional procedure 
and/or surgery to treat back and/or leg pain, which is providing significant pain 
relief  
7. Has unresolved major issues of secondary gain (e.g., social, financial, legal), as 
determined by the investigator 
8. Be pregnant (determined by urine testing unless female subject is surgically sterile 
or post-menopausal. If female, sexually active, and childbearing age, subject must 
be willing to use a reliable form of birth control.) 
 
B.4.  Treatment Groups 
Subjects meeting the study entrance criteria will be randomized to one of two study treatment 
groups in a 1:1 ratio: 
• Test treatment group with SGX-SCS programming approach 
• Control treatment group with Standard SCS programming approach 
 
B.5.  Study Design 
 
B.5.1.  Overall Design 
This is a post market, open-label, multi-center, prospective, randomized, controlled study 
to evaluate SGX-SCS in subjects with chronic, intractable pain of the lower back with 
moderate to severe limb pain.  Data at follow-up visits will be compared between the two 
treatment groups, and in reference to baseline assessments collected at the beginning of the 
study. 
 
B.5.2.  Bias Minimization 
This Investigational Plan and its associated documentation have been designed to minimize 
potential sources of bias.  Each Investigator’s qualification for meeting the requirements 
of this investigational plan will be reviewed prior to their participation in this investigation.  
Randomization of subjects to one of the two treatment groups will occur after the subject 
completes Baseline assessments in order to minimize selection bias.  
Each therapy, SGX-SCS programs and Standard SCS programs, will be programmed by 
clinical representatives of Stimgenics and Medtronic respectively, and in accordance with 
their standard therapy algorithms for optimal pain relief. This will minimize bias related to 
potential preference by a given clinical representative to a particular SCS therapy.  
  
B.5.3.  Comparison Groups 
Both groups in the study are active treatment groups. Treatment outcomes from subjects in 
the SGX-SCS group will be compared to those of the Standard SCS group.   
 

 
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B.5.4.  Blinding 
Due to the nature of the programs, it is not feasible to blind the subjects, implanting 
physicians or the clinical site personnel to the SGX-SCS programming and Standard 
programming SCS group assignments. Each SCS group will be programmed under the 
direction of physicians with support of clinical representatives of the Test and Control 
treatments, which may identify the type of treatment to study participants. Also, open 
communication about sensation of paresthesia and pain relief is important in adjusting 
program parameters to provide optimal pain relief for subjects. The assessments of device 
performance are done by the subjects and not by the site personnel so the lack of blinding 
of site personnel should not affect results as pain is the major assessment and subjects tend 
to describe pain truthfully since it affects their everyday life dramatically and not be 
influenced by knowledge of the device programming. Despite the inability to blind the 
study, past SCS studies indicate that there is no reason to believe that subjects and 
Investigators/clinical staff will be influenced one way or another by the knowledge that a 
particular SCS program has been used. 
 
B.5.5.  Sample Size 
Primary Endpoint Assessment occurs at the follow up visit 3 months after Device 
Activation.  Based on the primary endpoint requirement, the estimated sample size of this 
study is at least 100 total subjects (at least 50 subjects in the SGX-SCS group and at least 
50 subjects in Standard SCS group) who have passed screening requirements, have been 
randomized, and have completed the primary endpoint assessment.   
The clinical investigational plan requires a screening process for all subjects that provide 
written informed consent. These subjects will undergo screening to assess eligibility. 
Subjects may be excluded for various reasons during screening.  Accordingly, in order to 
include an estimated 125 subjects to the point of randomization and trial phase, 
approximately 250 subjects may need to be consented and enrolled to account for 
exclusions prior to randomization.  
 
B.5.5.1 Sample size rationale and statistical power 
The sample size estimate to determine primary endpoint is based on the primary 
objective of demonstrating non-inferiority of the test group to the control group.  
Established methods were followed in determining the non-inferiority criteria and the 
related sample size estimate 
• Test basis:  Farrington-Manning binomial test for non-inferiority 
• Estimated responder rate of 70% in the test group and 50% in the control 
group 
• Significance level, alpha, of 0.05 one-sided 
• Statistical power = approximately 90% or greater 
• Non-inferiority margin of 10% 
• Randomization:  1:1 

 
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Based on these assumptions, a minimum of 50 randomized and trialed subjects per 
treatment group (100 total) are required. 
 
B.5.5.2 Overall Sample Size and Enrollment 
Based on the primary endpoint requirement, a minimum of 50 subjects per treatment 
group are required (100 total). To account for a combined estimated attrition of 20% 
for subjects that do not complete the Trial Phase, and subjects that exit study before 
the 3-month primary endpoint visit, a total of 125 subjects would need to be 
randomized.    
To account for 50% attrition prior to randomization (including subject ineligibility 
after signing the informed consent and subject dropout), it is estimated that a total of 
up to 250 subjects would need to be enrolled in the study. 
 
B.5.6.  Study Duration 
This study is expected to last approximately 28 months.  Enrollment of subjects is expected 
to last 12 months. Subjects who are expected to complete will commit to it for 
approximately 8 months. This consists of Baseline assessments, up to 10 days of trial 
stimulation, and 6 months of treatment following implantation and activation of the device. 
All subjects who remain implanted at the time of Study Completion will be offered to return 
for an additional visit 12-months after device activation.  
 
B.5.7.  Interim Administrative Analysis  
 
For the purposes of business decisions and planning purposes (e.g., to provide an update to  
third-party investors), an administrative analysis will be performed.  The results of this 
analysis will not be widely distributed, and access will be limited to those persons with a 
“need to know”.  Access will be restricted from those involved with the study conduct or 
management to prevent the introduction of bias.  The administrative analysis will not be 
used to modify the trial or stop early for potential benefit. As there is no chance of early 
stopping, the type I error rate is not affected. Limiting changes to the protocol and access 
to the interim administrative analysis also prevents operational bias due to knowledge of 
interim results. 
 
 
B.6.  Enrollment, Assessments, Randomization, and Clinical Procedure 

 
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Enrollment of subjects will occur at the clinical sites after Institutional Review Board (IRB) 
approvals, and when written informed consent from subjects has been obtained.  Prior to 
enrollment, Investigators and clinical site staff will approach subjects, who have been 
determined to be candidates for SCS therapy and talk about potential participation in the study.  
Following informed consent, the eligibility of subjects to participate in the study will be 
assessed according to inclusion and exclusion criteria outlined in this Investigational Plan.  
Various assessments including pain intensity, evaluation of medical history and records, and 
the Investigator’s clinical judgment will be used in the selection process.  
 
B.6.1.  Summary of Study Protocol 
Potential study subjects will be identified from a pool of candidates for SCS therapy that 
are either affiliated with or referred to the clinical sites.  Advertisements of the study may 
be used for recruitment purposes, upon approval of the patient recruitment materials by the 
study IRB(s). An informed consent form (ICF) will be given to the potential subject for 
private evaluation. The Investigator or Study Clinical Staff will be available to respond any 
questions the potential subject may have during evaluation of the ICF. Potential study 
subjects willing to participate in the study will visit the study site for providing written 
consent and for evaluation of eligibility based on inclusion and exclusion criteria.  Once a 
consented subject is deemed qualified to participate in the study, baseline assessments and 
randomization will occur followed by scheduling of the trial stimulation phase with the 
assigned treatment group.  Subjects who complete a successful SCS trial phase will be 
scheduled to receive a permanent implant of leads and the INS and will undergo 6 months 
of stimulation delivery with assessments at 1, 3, and 6 months after the activation of the 
therapy. 
Baseline assessments will include measures for pain intensity, use of medication, extent of 
disability, and quality of life. 
Following completion of the baseline assessment, study subjects will be randomized in a 
1:1 ratio to either the SGX-SCS programming group or the Standard SCS programming 
group.  
After randomization, subjects will undergo a Trial Phase lasting up to 10 days to determine 
subject’s response to assigned treatment group. Temporary or permanent leads and an 
external neurostimulator (ENS) will be used during the Trial Phase. Subjects will evaluate 
the assigned treatment group based on pain intensity under optimal parameters. Those who 
have a "successful Trial Phase" (defined as a 40% or greater pain reduction from Baseline 
in their back pain) will proceed to permanent implantation of a SCS system to evaluate the 
assigned treatment group. 
The implanted INS will be activated within 14 days after surgical procedure and SCS 
therapy will be delivered for the next 6 months. Activation of the device marks the initial 
time point for effectiveness evaluation of the study therapies after implantation. 
Assessments of pain intensity, use of medication and adverse events will be made at 1 
month following Device Activation.  At 3 and 6 months after Device Activation, subjects 
will be assessed for pain intensity, adverse events, extent of disability, use of medication, 
and quality of life. Patient Global Impression of Change, and subject satisfaction will also 
be recorded at 3 months after Device Activation. All subjects who remain implanted at the 

 
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time of Study Completion will be offered to return for an additional visit 12-months after 
device activation. 
Figure 1 summarizes the sequence of study-related assessments, procedures, and activities. 
 
B.6.2.  Consent/Enrollment 
Written informed consent for participation in the study must be obtained from subjects 
before initiation of any study-related activities, including those that assess eligibility.  
Following informed consent, subjects will be assigned a unique subject identification 
number and will be considered to be enrolled in the study.  Eligibility for advancing to the 
next stage of the study will be evaluated by the site Investigator based on the defined 
inclusion and exclusion criteria. Subjects will be assessed for pain intensity and disability.  
 
B.6.3.  Entry Criteria Evaluation (0-14 days from Enrollment) 
The eligibility of subjects who have consented participation will be assessed based on the 
inclusion and exclusion criteria.  Study subjects must meet all of the study inclusion criteria 
and none of the study exclusion criteria to be eligible.  Assessments for eligibility include 
average pain intensity (which will be used as Baseline pain intensity), medication usage, 
medical records and history, and the Investigator’s clinical judgment.  Subjects with 
confirmed eligibility will proceed to Baseline assessment, while subjects who do not will 
be discontinued from the study.   
 
B.6.4.  Baseline 
Before a subject is randomized, a subject will be requested to fill out standard 
questionnaires that will assess extent of disability, use of medications, and quality of life.  
The medical and surgical history of the subject will be collected. At this visit and 
subsequent visits, the subject will be assessed for adverse events, medication usage and be 
reminded to not increase pain medications from baseline through the 3-Month Visit.  
Pre-operative assessments will follow the standard of care for SCS therapy and be 
determined by the site Investigator.  
 
B.6.5.  Randomization 
Subsequent to completing Baseline assessments, qualifying subjects will be randomly 
assigned to either one of the two study treatment groups: SGX-SCS programming or 
Standard SCS programming (active comparator).  Randomization will be stratified by 
gender and whether the subject has bilateral or unilateral leg pain at Baseline. 
Randomization will be done at each study site by randomly permuted blocks. 
 
B.6.6.  SCS Trial Phase 
Subjects will undergo a Trial Phase with the randomly assigned treatment group.  The Trial 
Phase will last up to 10 days.  Percutaneous leads will be placed in the epidural space at a 

 
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vertebral level based on the subject’s pain condition and pain pattern as described in the 
Physician Implant Manual. Stimulation will be delivered from an external neurostimulator 
(ENS).   
Anterior-posterior (AP) and lateral X-ray imaging will be done following lead implantation 
at the beginning of the Trial Phase and when significant lead migration is suspected. 
Stimulation therapy will be as follows for each study arm: 
• For Standard SCS: stimulation parameters will be trialed according to standard 
practice as described in the IntellisTM labeling/manuals.   
• For SGX-SCS: As with Standard SCS programming, subjects will be given 
multiple program groups to try. Each SGX-SCS program group will have multiple 
parameters.  The stimulation parameters will be within the specifications described 
in the IntellisTM labeling/manuals.  Each SGX-SCS program group has at least two 
programs with different pulse rate in the 50 to 1,000 Hz range and each having a 
maximum pulse width of 1 ms. The subject will progress through each of the 
program groups until satisfactory pain relief has been reached. The subject will be 
able to adjust the amplitude of the signals as deemed needed to obtain pain relief.  
If sufficient pain relief is not achieved with the initial program group, the subject 
will be instructed to trial another SGX-SCS program group. 
Adjustments to a program group may be made based on patient feedback following the 
trialing of a particular program group or set of stimulation parameters. The primary factor 
for assessing response to a given program group or stimulation parameters is the subject’s 
self-reported pain relief.  Adjustments to therapy will be attempted until at least 50% self-
reported back pain reduction from baseline is achieved or until conclusion of the trial phase 
(no more than 10 days). Subjects will be assessed for adverse events and medication usage.  
 
B.6.7.  End of Trial Assessment  
At the end of the Trial Phase, subjects will be assessed for pain intensity under optimal 
therapy parameters. Anterior-posterior (AP) and lateral X-ray imaging may  be done at the 
end of the Trial Phase.) The subject will be assessed for adverse events and medication 
usage. 
Those who have a "successful Trial Phase" (defined as a 40% or greater pain reduction 
from Baseline in their back pain) will proceed to permanent implantation of a SCS system 
to evaluate the assigned therapy, and permanent implantation of the IntellisTM SCS system 
will be scheduled. A threshold of 40% for the Trial Phase was predetermined as the 
minimum pain reduction that warrants consideration of a permanent implant and an 
opportunity to achieve a 50% pain reduction as defined in the Individual Subject Success 
criterion (see Section B.7.3).)  
Data from subjects who did not achieve 40% or greater pain reduction in back and do not 
receive permanent implantation will be carried forward toward the primary endpoint. These 
subjects will exit the study after being followed up for two weeks after explant of the leads 
to assess adverse events. 
 

 
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B.6.8.  Permanent Device Implant (0-60 days from end of successful Trial Phase) 
As described in section B.6.7, subjects who underwent a successful trial of the assigned 
SCS therapy and who agreed to continue into the next stage of the study will proceed to 
permanent implantation stage.  
Permanent percutaneous leads will be placed in the epidural space at a vertebral level based 
on the subject’s pain condition and pain pattern as described in the IntellisTM Physician 
Implant Manual. The INS will be implanted by a trained physician according to standard 
practice and following the Physician Implant Manual for the device.  Anterior-posterior 
(AP) and lateral X-ray imaging will be obtained.  Standard practice of a study site for 
prophylactic pre-surgery antibiotics and post-surgery pain medications will be followed). 
Subjects will be assessed for adverse events and medication usage.  
 
B.6.9.  Device Activation (0-14 days following Permanent Implant) 
Clinical personnel at the site will assess if healing of surgical wounds is sufficiently 
appropriate to start charging and programming of the INS. The INS will be initially 
programmed to the group therapy or set of stimulation parameters that provided adequate 
pain relief during the Trial Phase. Adjustments to therapy may be made based on patient 
response to a program group or set of stimulation parameters. The subject will be provided 
with instructions on how to operate the charger and patient remote control at this visit.  
Subjects will be assessed for adverse events and medication usage.  
 
B.6.10.  Unscheduled Visits 
Unscheduled visits may occur at any time during the study for the assessment of possible 
adverse events, changes in pain medication, and programming adjustments.  Each 
unscheduled visit will be documented and recorded on an eCRF. 
 
B.6.11.  Telephone Calls 
Subjects will be contacted by the study coordinator, via a telephone call, before each study 
visit. The study coordinator will check on the well-being of the subject, remind the subject 
of the upcoming scheduled visit, remind the subject not to change pain medication usage 
prior to the scheduled visit, and remind the subject to contact the Investigator/study staff 
should he/she have any concerns or questions. The telephone calls should be made two to 
three weeks before the scheduled visit. 
 
B.6.12.  1 Month After Device Activation (± 10 days) 
Subjects will visit the study site where they will be assessed for pain intensity.  
Programming adjustments may be made, as needed. Anterior-posterior (AP) and lateral X-
ray imaging may be done if significant lead migration is suspected. Subjects will be 
assessed for adverse events and medication usage.  
 

 
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B.6.13.  3 Months After Device Activation (± 15 days) 
Subjects will visit the study site where they will be assessed for pain intensity, extent of 
disability, use of medication, quality of life, Patient Global Impression of Change, and 
subject satisfaction. Paresthesia generated by the stimulator will be assessed. Programming 
adjustments may be made, as needed. Anterior-posterior (AP) and lateral X-ray imaging 
may be done if significant lead migration is suspected. Subjects will also be assessed for 
possible adverse events and medication usage.  
 
B.6.14.  6 Months After Device Activation (± 30 days) 
The follow-up visit 6 Months after Device Activation is the final scheduled study visit. 
Subjects will visit the study site where they will be assessed for pain, extent of disability, 
quality of life, Patient Global Impression of Change, and subject satisfaction.  Paresthesia 
generated by the stimulator will be assessed. Programming adjustments may be made, as 
needed.  Subjects will also be assessed for possible adverse events and medication usage.   
If there are no ongoing study related adverse events, the subject will complete the study at 
this visit. In situations where there is an ongoing study related adverse event, subjects will 
be followed until resolution of that adverse event or determination that the subject’s 
condition is stable, at which point the Study Completion Clinical Research Form (eCRF) 
should be completed. 
Beyond Study Completion, all subjects who remain implanted at the time of Study 
Completion will be offered to return for an additional visit 12-months after device 
activation. Following the last scheduled study visit, subjects will be followed by the 
Investigator at regular intervals, as dictated by standard of care at each site, in order to 
facilitate pain management, stimulation adjustments, possible revisions and/or 
replacements of neurostimulation components. Any additional non-study related 
monitoring of the subject will be the responsibility of the subject’s personal physician, as 
dictated by reasonable medical care. 
 
B.6.15. 12 Months After Device Activation (± 30 days) 
Subjects will be offered an additional visit at 12 months after device activation. The visit 
will consist of the same assessments as the 3 and 6 month visits. Subjects will visit the 
study site where they will be assessed for pain, extent of disability, quality of life, Patient 
Global Impression of Change, and subject satisfaction.  Paresthesia generated by the 
stimulator will be assessed. Programming adjustments may be made, as needed.  Subjects 
will also be assessed for possible adverse events and medication usage.  In situations where 
there is an ongoing study related adverse event, subjects will be followed until resolution 
of that adverse event or determination that the subject’s condition is stable.  
Beyond the 12 month visit, there will be no additional scheduled follow-up visits in the 
study.  Following the last scheduled study visit, subjects will be followed by the 
Investigator at regular intervals, as dictated by standard of care at each site, in order to 
facilitate pain management, stimulation adjustments, possible revisions and/or 
replacements of neurostimulation components. Any additional non-study related 

 
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monitoring of the subject will be the responsibility of the subject’s personal physician, as 
dictated by reasonable medical care. 
 
 
B.6.16  Other Assessments and Information 
At any time during the study, if lead migration is suspected, the subject may have additional 
AP and lateral X-rays taken to confirm the new lead position in order to aid the Investigator 
in determining a course of action. 
Paresthesia testing may also be performed to assess lead location and therapy coverage of 
pain areas. Programming adjustments may be made based on patient feedback following 
assessment. 
Additional information on Medication Usage: 
• The investigator will instruct all subjects to take the Baseline doses of pain 
medication until the 3-Month Visit.  However, after Device Activation Visit, the 
Investigator may reduce the dose of pain medication if the subject is benefitting 
greatly from SCS and not benefitting from Baseline dose pain medication. 
o Subjects should not fluctuate medication usage nor dosages even if the dose 
is at or below Baseline doses. The investigator will instruct all subjects to 
maintain stable dosing of medication for at least two weeks prior to 
scheduled follow-up visits. 
• Acetaminophen, NSAIDs or other pain medications (new prescriptions or greater 
than Baseline doses) may only be taken for an acute condition and for a limited 
duration. For each type of pain medication, dosing should not exceed the maximum 
daily dosage recommended by the manufacturer and usage should not continue 
beyond 5 days. Should acute pain medication usage coincide with a follow-up visit, 
the visit will be postponed until two weeks after acute pain medication usage has 
been stopped. 
• Following trial and permanent implants, the clinical site’s standard practice for 
prophylactic pre-surgery antibiotics and post-surgery pain medications will be 
followed. Investigators will instruct subjects not to change usage of any other 
concomitant pain medications. 
 
B.6.17.  Device Explant 
At any time during the study, a subject may elect to withdraw from the study and have the 
SCS device system explanted.  Additionally, an Investigator may elect to explant a device 
due to an adverse event. 
The Investigator must follow the appropriate guidelines set forth by the Medtronic for 
returning the explanted device and/or lead(s) as well as the accessories (charger, patient 
remote control). 
 

 
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B.6.18.  Early Subject Withdrawal 
Although efforts will be made by Investigators and study staff to encourage subjects to 
remain enrolled in the study, subjects may withdraw early from the study for a number of 
reasons, including but not limited to: 
• Failure of SCS Trial Phase 
• Subject request 
• Investigator request 
• Subject lost to follow-up 
• Subject’s death 
• Adverse events (e.g., intolerable adverse event occurrence that forces subject to 
stop participation in the study) 
If a subject is considering withdrawing from the study due to unsatisfactory effectiveness 
of the assigned treatment, the Investigator will make attempts to improve therapy during a 
study visit. When a subject is withdrawn early from the study, a Study Termination eCRF 
will be completed describing the reason for discontinuation.  Study staff will contact 
subjects to remind them about their scheduled visits and make sufficient efforts to locate a 
subject that is not responding to a contact call. If a subject has withdrawn consent for the 
study, or is lost to follow-up, the completion of this visit is not required.  In situations 
where study withdrawal is due to an adverse event, subjects will be followed until 
resolution of the adverse event or determination that the adverse event is not likely to 
change. 
 
B.6.19.  Study Completion 
All subjects enrolled in the study are expected to complete all scheduled visits through the 
follow up visit 6 months after Device Activation.  A Study Completion eCRF should be 
completed at the end of this visit. If the subject decides to decline the additional 12 month 
visit and there is an ongoing study related adverse event, subjects will be followed until 
resolution of that adverse event or determination that the adverse event is not expected to 
change. 
Subjects who decide to complete the 12 month visit would also be followed equivalently 
in cases of ongoing study related adverse events.  
 
B.6.20.  Study Suspension and Termination 
Subjects will be considered to have completed all study requirements following the 
completion of the follow up visit 6 Months after Device Activation.  Each clinical site will 
be considered to have completed study requirements at the end of the required monitored 
close out visit.  The study will be considered terminated when all of the requirements of 
this Investigational Plan have been fulfilled, all close out visits have been completed and 
all Sponsor and Investigator reports have been issued and reported to the IRB. 
Stimgenics, the Investigators, or the IRB(s) may suspend or terminate the study early at 
any time.  If the study is suspended or terminated prematurely, all subjects that are still 
enrolled will be terminated from the study. A Study Completion eCRF will be completed 

 
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noting that the study has been terminated.  If there is an ongoing adverse event related to 
the device or treatment, the subject will be followed until resolution of the adverse event 
or determination that the adverse event is not likely to change.  
Subsequent follow-up of the subjects after study completion will be the responsibility of 
the subject’s personal physician.   
Stimgenics reserves the right to terminate the study but intends only to exercise this right 
for reasons related to the protection of subjects or valid scientific or business reasons.  
Stimgenics will notify Investigators and IRBs in writing in the event of study termination.   
Stimgenics reserves the right to stop the enrollment of subjects at any clinical site at any 
time after the clinical site initiation. Possible reasons for suspending or terminating a 
clinical site may include, but are not limited to: 
• Non-compliance by Investigator  
• Failure to obtain proper written informed consent 
• Repeated failure to complete or submit eCRFs in a timely manner 
• Failure to report SAEs to the Sponsor within 48 hours of knowledge of the event 
and to reviewing IRB in accordance with its policies 
• Repeated failure to comply with clearance of queries generated during monitoring 
of the study 
• Inactivity 
 
B.7.  Study Endpoints 
 
B.7.1.  Definition of Analysis Populations  
• Intent to Treat (ITT): All randomized subjects. 
• Modified Intent to Treat (mITT): All randomized subjects who complete the Trial 
Phase. 
• Per-Protocol (PP):  All subjects who complete the Trial Phase and who complete 
the study without any major protocol deviations (that would render their data 
unevaluable).  
The primary analysis of the primary and secondary endpoints will be performed on 
the ITT population. Supportive analyses will be performed for the mITT and Per-
Protocol population.  
 
B.7.2.  Effectiveness Assessment Definitions 
• Primary Effectiveness Assessment:  For subjects who have a successful Trial Phase 
and receive a permanent implant, the Primary Efficacy Assessment occurs at the 
follow up visit 3 months after Device Activation.  For subjects who do not have a 
successful Trial Phase, the Primary Efficacy Assessment occurs at the end of the 
Trial Phase.  
• 6-month Secondary Effectiveness Assessment:  For subjects who have a successful 
Trial Phase and receive a permanent implant, the 6-month Secondary Efficacy 

 
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Assessment occurs at the follow up visit 6 months after Device Activation.  For 
subjects who do not have a successful Trial Phase, the 6-month Secondary Efficacy 
Assessment occurs at the end of the Trial Phase.  
 
B.7.3.  Primary Endpoint 
Pain rating on the 10 cm Visual Analog Scale is considered the primary outcome 
measure.  VAS is the most widely used outcome measure in assessing pain due to its 
documented reliability and validity, ease in administration, and minimal training 
requirements for the administrator. 
• Individual Responder:  A decrease in back pain VAS by at least 50% 
at 3 months Post-Permanent Device Activation as compared with 
Baseline.  
Overall Study Success:  The percentage of Individual Responders in the test 
group is shown to be statistically non-inferior to the percentage in the control 
group.  
 
B.7.4.  Secondary Endpoints 
The following secondary endpoints will be evaluated:  
• Comparison of the percentage of Individual Responders between the test and 
control groups in a statistical test of superiority 
• Comparison of change from Baseline in back pain score (VAS) determined at the 
3-month visit after device activation, between test and control in a statistical test of 
non-inferiority.  This is calculated as: Change from Baseline in Back Pain VAS = 
3-Month Visit Pain VAS – Baseline Pain VAS. A negative result reflects a decrease 
in the Pain VAS, while a positive result reflects an increase in Pain VAS.  
• Comparison of Back Pain Treatment Success (responder rate), measured as subjects 
with at least a 50% reduction in Back Pain VAS, evaluated at 6 months after device 
activation, between test and control  
• Comparison of mean change from Baseline in Back Pain VAS, evaluated at 6 
months after device activation, between test and control 
• Comparison of mean change from Baseline in disability as measured by Oswestry 
Disability Index (ODI), evaluated at 3 months after device activation between test 
and control 
• Frequency of treatment emergent adverse events 
 
B.7.5.  Additional Data Collection  
These following data will be collected: 
• Comparison of mean change from Baseline in Back Pain VAS, evaluated at 1-
month after device activation, between test and control 

 
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• Comparison of mean change from Baseline in Leg Pain VAS, evaluated at 1, 3, and 
6 months after device activation for subjects with baseline leg pain VAS score ≥ 5 
between test and control 
• Comparison of Leg Pain Treatment Success, measured as at least a 50% reduction 
in Leg Pain VAS, evaluated at 3 and 6 months after device activation for subjects 
with baseline leg pain VAS score ≥ 5 between test and control 
• Subject Satisfaction, evaluated at 3 and 6 months after device activation 
• Comparison of patient satisfaction between two arms 
• Patient Global Impression of Change, evaluated at 3 and 6 months after device 
activation 
• Comparison of Patient Global Impression of Change between two arms 
• Comparison of ODI change from baseline at 6 months after device activation 
between the two arms 
• Comparison of quality of life (QoL) change (from PROMIS Scale - Global Health) 
from baseline at 3 and 6 months after device activation between the two arms 
• Quality of paresthesia at 3 and 6 months, comparison between test and control  
• Activity level based on IntellisTM adaptive data log 
Details on additional data collection for the 12 month visit will be provided in a 
separate statistical analysis plan.  
 
B.8.  Evaluation Criteria 
 
B.8.1.  Effectiveness 
Results of the tests and standard questionnaires will be recorded in Case Report Forms at 
Baseline and during follow-up visits.  Changes from Baseline will be calculated and 
compared between the two groups.   
Effectiveness will be measured for each subject using the following tests: 
• Pain 
– Visual Analog Scale (VAS, 10 cm) at Baseline, End of Trial Phase, Months 1, 
3, and 6  
• Disability 
– Oswestry Disability Questionnaire 
• Quality of Life 
– PROMIS Scale v1.2- Global Health 
• Impression of Change in Quality of Life 
– Patient Global Impression of Change 
• Satisfaction with Therapy 
– Subject Satisfaction Questionnaire 
• Paresthesia generated by the stimulator 

 
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– Paresthesia Questionnaire 
 
Study personnel will be appropriately trained for administration of each test. Details on 
evaluation criteria for effectiveness for the 12 month visit will be provided in a separate 
statistical analysis plan.  
 
 
B.8.2.  Definition of Success 
 
The subject’s self-reported pain intensity score based on the 10 cm Visual Analog Scale 
(VAS) is considered the outcome measure for the efficacy component of the primary 
endpoint. VAS is a widely used outcome measure in assessing pain. It is a reliable and valid 
method, which is easy to administer, and requires minimal training for the test 
administrator. VAS scores will be collected for both back and leg pain.   
Study success will be declared if the non-inferiority test for the primary effectiveness 
endpoint is statistically significant.  
There are no additional pre-specified subject or study-level success criteria for secondary 
and tertiary endpoints.  
 
B.8.3.  Safety 
Safety will be assessed by characterizing adverse events at all study visits with descriptive 
statistics. 
 
B.8.3.1 Definitions 
An adverse event (AE) is any untoward medical occurrence in a subject associated 
with the use of the therapy under the study whether or not related to IntellisTM SCS 
system or the study procedures. An AE is also any event related to any underlying 
medical condition, present at baseline, which increases in severity or frequency by a 
clinically meaningful amount during the study as determined by the Investigator.  
For all adverse events, the Investigator will provide an assessment of the adverse event, 
its seriousness, treatment/intervention provided, relationship to the device/procedure, 
and resolution. 
As the efficacy measures in this study are back and leg pain, back and leg pain do not 
need to be reported as an adverse event unless it meets the definition of a serious 
adverse event. Investigators may, however, report any other pain-related adverse 
events during the study.   
Pre-existing conditions will not be reported as an adverse event unless there has been 
a substantial increase in the severity or frequency of the problem, which has not been 
attributed to its natural history. 
A serious adverse event (SAE) is an adverse event that  

 
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• Leads to death 
• Leads to serious deterioration in the health of the subject, that either results in  
o a life-threatening illness or injury (life-threatening is defined as at risk 
of death at the time of the event), or 
o a permanent impairment of a body structure or a body function, or 
o in-patient hospitalization or prolongation of existing hospitalization (in-
patient hospitalization is defined as a hospital admission for a period of 
greater than 24 hours), or  
o medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
• Leads to fetal distress, fetal death, or a congenital abnormality or birth defect 
Those known adverse events related to the device, procedure or therapy are listed in 
the section C. (Risk Analysis) of this Investigational Plan. 
 
B.8.3.2 Reporting 
All AEs and SAEs will be assessed and captured from enrollment through the 
completion of the study on the Adverse Event Case Report Form (AE-eCRF).  AEs 
and SAEs will be reported as required by the IRB. However, as would be the common 
practice when using commercial medical devices, device -related AEs may be reported 
by the site (per their institutional policy) to the Customer Service or Technical Support 
of Medtronic as specified in the manufacturer's labeling/manuals. 
All Adverse Events (see list in section C.1.) reported during the study will document 
seriousness, treatment/intervention provided, relationship to the device/procedure, and 
resolution.   
This is a post market, open-label study so Data Monitoring Committee will not be 
used.  
  
B.9.  Data Collection and Analysis 
 
B.9.1.  Data Collection 
Study data will be collected using a secure Electronic Data Capture system meeting the 
requirements of 21 CFR part 11. Each data field completed via the EDC system is expected 
to have a verifiable source document.  The clinical site will enter directly the data on 
outcome variables as well as adverse events should they occur.  Subject confidentiality will 
be maintained, and each subject will be identified only by the assigned study subject 
number.  Subject names will not be published. 
Data collection is summarized in Table 1. 

 
Stimgenics SGEN-2018PM2              
            
 
 
 
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24 
Table 1. Schedule of Study Activities 
 
Pre-Trial Phase 
Trial Phase 
 
 
 
Activity 
Enrollment 
Baseline  
Start Trial 
Phase 
End Trial 
Phase (up 
to10 days 
after start of 
trial) 
Permanent 
Implant (up 
to 60 days 
after end of 
trial) 
Device 
Activation 
(0-14 days 
after 
implant) 
1-month visit 
(±10 days 
after 
activation) 
3 months 
visit (±15 
days after 
activation) 
6 months 
visit (±30 
days after 
activation) 
Optional 12 
months visit 
(±30 days 
after 
Informed Consent* 
X 
 
 
 
 
 
 
 
 
 
Pain Intensity Evaluation 
(VAS) 
X 
 
 
X 
 
 
X 
X 
X 
X 
Medication Use 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/Surgical History 
 
X 
 
 
 
 
 
 
 
 
Eligibility Criteria 
Evaluation 
X 
 
 
 
 
 
 
 
 
 
Disability Assessment (ODI) 
 
X 
 
 
 
 
 
X 
X 
X 
Quality of Life Assessment 
(PROMIS) 
 
X 
 
 
 
 
 
X 
X 
X 
AP/Lateral x-ray imaging 
 
 
X 
[X] 
X 
[X] 
[X] 
[X] 
[X] 
[X]  
Paresthesia Questionnaire 
 
 
 
 
 
 
 
X 
X 
X 
Patient Global Impression of 
Change 
 
 
 
 
 
 
 
X 
X 
X 
Subject Satisfaction 
 
 
 
 
 
 
 
X 
X 
X 
Adverse Event Monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Programming 
 
 
X 
 
 
X 
[X] 
[X] 
[X] 
[X]  
Device Follow-up Log 
 
 
 
 
 
 
 
[X] 
[X] 
[X] 
Study Completion 
 
 
 
Xa 
 
 
 
 
X 
 
a For subjects that do not have a successful Trial Phase. [X] Optional activity. 
*For subjects consented prior to the IRB approval of the revised consent, they may be reconsented at any study visit. 
 

 
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25 
B.9.2.  Statistical Analysis 
Descriptive statistics will be used to summarize baseline and outcome data collected during 
the study.  Continuous variables will be summarized using means, standard deviations, and 
ranges.  Categorical variables will be summarized in frequency distributions. 
 
B.9.2.1 Primary Analyses 
The primary efficacy endpoint will be evaluated with a Farrington-Manning binomial 
test for non-inferiority at the one-sided 0.05 alpha level. 
H0: The percentage of subjects (P) who achieve a 50% improvement in their back 
VAS pain score at 3 months in the Test group is inferior to that in the Control 
group. 
PTest  ≤  PControl - 10% 
H1: The percentage of subjects (P) who achieve a 50% improvement in their back 
VAS pain score at 3 months in the Test group is not inferior to that in the 
Control group. 
PTest  >  PControl - 10% 
A 10% margin has been previously used in a similar study.8 Meeting the statistical 
threshold for this test based on a 10% margin should produce clinically acceptable 
results.  
 
B.9.2.2 Secondary Analyses 
The following secondary endpoints will be evaluated: 
• If the primary efficacy endpoint in the test group is found to be non-inferior to 
that in the control group, then a secondary endpoint will evaluate whether the 
proportion of subjects who achieve a 50% improvement in their back pain 
VAS score at 3 months in the test group is superior to that in the control 
group.  A superiority test based on the difference in proportions will be 
performed based on the following null hypothesis, with a one-sided p-value of 
0.05 or less considered evidence of statistical significance. 
H0: 
The proportion of subjects (P) who achieve a 50% improvement in their 
back pain VAS score at 3 months in the Test group is less than or equal 
to that in the Control group. 
PTest   ≤  PControl  
H1: 
The proportion of subjects (P) who achieve a 50% improvement in their 
back pain VAS score at 3 months in the Test group is greater than that 
in the Control group. 
PTest  >  PControl  
 
 

 
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• Change in mean VAS will be evaluated with two-sample t-test of non-
inferiority in means with a 0.65 cm margin at 3 months. 
H0: The change (C) in subject’s VAS pain intensity score relative to baseline at 
the Primary Efficacy Assessment in the Test group is inferior to that of 
subjects in the Control group (active control). 
CTest  ≥  CControl - 0.65 cm 
H1: The change (C) in subject’s VAS pain intensity score relative to baseline at 
the Primary Efficacy Assessment in the Test group is not inferior to that of 
subjects in the Control group (active control). 
CTest  <  CControl - 0.65 cm 
The non-inferiority margin of 0.65 cm was selected based on a previous study of a 
similar therapy against traditional SCS.8 In that study, the experimental therapy 
showed a 4.9 point improvement while traditional SCS showed a 3.6 point 
improvement for a difference of 1.3 points. Taking 50% of this treatment effect 
yields the margin of 0.65.   
The following secondary endpoints do not have an associated hypothesis, and no 
significance level will be assigned to statistical tests that may be performed. 
• 
Comparison of Back Pain Treatment Success (responder rate), measured as 
subjects with at least a 50% reduction in Back Pain VAS, evaluated at 6-months 
after device activation, between test and control: 
• 
Comparison of mean change from Baseline in Back Pain VAS, evaluated at 6-
months after device activation, between test and control 
• 
Comparison of mean change from Baseline in disability as measured by 
Oswestry Disability Index (ODI), evaluated at 3- months after device 
activation between test and controlFrequency of treatment emergent adverse 
events  
Data will be summarized in frequency distributions by study group of each 
adverse event (AE) type and by the percentages of subjects with one or more 
of each AE type.  
 
 
B.9.2.3 Additional Data 
• Efficacy at 1-month: The primary efficacy endpoint will be reassessed at 1-
month 
• Leg pain relief: Efficacy will be assessed for reduction of leg pain VAS score 
vs baseline evaluated at 1-, 3-, and 6-months after device activation for subjects 
with baseline leg pain VAS score ≥ 5 between test and control 
• Responder rate for leg pain: The proportion of subjects that respond to 
treatment defined as having at least a 50% reduction in leg pain VAS relative 

 
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to baseline, evaluated at 3- and 6-months after device activation for subjects 
with baseline leg pain VAS score ≥ 5 between test and control 
• Satisfaction with Therapy:  Subject Satisfaction will be compared between the 
treatment groups at 3- and 6-month visits after device activation. 
• Patient Global Impression Change:  The Patient Global Impression of Change 
from Baseline to follow-ups at 3- and 6-month visits after device activation will 
be compared between the treatment groups. 
• Oswestry Disability Index (ODI):  The changes in ODI from Baseline to 6-
months will be summarized as continuous variables and compared between the 
treatment groups.  
• Quality of Life:  The changes in the PROMIS instrument from Baseline to 
follow-ups at 3- and 6-months will be summarized as continuous variables and 
compared between the treatment groups. 
• Paresthesia Questionnaire: Questions about the paresthesia will be used at 3- 
and 6-month visits and compared between test and control  
Details on additional data for the 12 month visit will be provided in a separate 
statistical analysis plan.  
 
B.9.2.4 Handling of Missing Data 
 
Missing data will be minimized by rigorous follow-up and investigator and site 
training. Additionally, for subjects who do not have a successful Trial Phase, 
results from the Trial Phase will be utilized for the primary endpoint as described 
in Section B.7.2.  Effectiveness Assessment Definitions. Any other data will be 
imputed via Multiple Imputation. Additionally, sensitivity analyses for missing 
data will be performed. Unless otherwise specified, all other analyses will be 
based on the evaluable data with no imputation.  
 
Details on imputation will be provided in a separate statistical analysis plan.  
 
 
C.  Risk Analysis 
C.1.  Description and Analysis of All Increased Risks to Subjects 
Spinal Cord Stimulation (SCS) Risks: 
SGX-SCS programming approach will be used with commercially available, FDA approved 
IntellisTM SCS system within approved indications for use. Anticipated potential adverse events 
resulting from the study are expected to be in line with adverse events already documented for 
SCS using a Standard programming approach.  
There are known risks associated with the use of any SCS system.  Known risks are associated 
with the implant procedure, the stimulation, the implanted device (not associated with 

 
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stimulation) and external devices such as the charger and remote control. These are typical of 
commercial SCS systems. Subjects will be informed of these anticipated risks in the study 
consent process. 
 
Risks of Surgery 
Implanting a neurostimulation system has risks similar to spinal procedures, including spinal 
fluid leak (spinal fluid collection under the skin), headaches, swelling, bruising, bleeding, 
infection, or paralysis.  
Subjects on anticoagulation therapy may be at higher risk for problems after surgery such as 
hematomas that could result in paralysis. 
Spinal Cord Stimulation Risks 
The implantation of a spinal cord stimulation system involves risks that are similar to other 
spinal procedures. In addition to those normally associated with surgery, implantation or use of 
a neurostimulation system includes, but is not limited to, the following risks: 
• Allergic or immune system response to the implanted materials 
• Infection 
• Lead or neurostimulator erosion through the skin or migration 
• Leakage of cerebrospinal fluid 
• Loss of pain relief may return patients to their underlying pain condition 
• Persistent pain at the neurostimulator site 
• Placement of the epidural lead is a surgical procedure that may expose patients to 
risks of epidural hemorrhage (bleeding), hematoma, or paralysis 
• Radicular chest wall stimulation 
• Seroma (fluid collection in pocket where stimulator is placed) or hematoma at the 
neurostimulator site 
• Change in stimulation, possibly related to cellular changes around the electrode(s), 
shifts in electrode position, loose electrical connections, lead fractures, which has 
been described by some patients as uncomfortable stimulation (jolting or shocking 
sensation) 
• Over time there could be changes in the level of symptom control. In most cases, 
the physician can correct these changes without surgery. 
• Formation of excessive tissue around the lead in the epidural space can result in 
delayed spinal cord compression and paralysis, requiring surgical intervention. 
Time to onset can range from weeks to many years after implant. 
• The safety of this therapy is unknown for pregnancy, unborn fetus, or delivery 
• Stimulation-dependent gastrointestinal symptoms such as diarrhea, incontinence or 
constipation 
• Stimulation-dependent bladder symptoms such as urinary retention, incontinence 
or frequency 
• Unexpected changes in stimulation - Electromagnetic interference, changes in 
posture, and other activities can cause a perceived increase in stimulation 

 
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System Revision Risk 
The Intellis AdaptiveStim Neurostimulator may require replacement in 9 years or earlier, 
regardless of the number of times the neurostimulator is recharged.  It is possible that the system 
will need to be revised (explanted, replaced, or repositioned) earlier than 9 years.  Possible 
reasons for revision/explant may include infection, malfunction, and migration of the system 
components.  The risks associated with system revision are equivalent to the commercially 
available systems.    
Pregnancy Risks 
Pregnant women are not able to take part in this study.  Female subjects must agree to not 
become pregnant during the study by using a medically acceptable method of birth control. If a 
subject becomes pregnant during this study, there may be risks to the unborn child that are not 
yet known.  Subjects will be advised and encouraged to notify the study doctor immediately if 
they think they are or have become pregnant.  Subjects that become pregnant during the study 
will be instructed to turn the neurostimulator “OFF” and will be exited from the study. 
Radiographic Imaging 
As part of the study, subjects may  be required to have fluoroscopic or X-ray images taken of 
their thoracic spine  in addition to the imaging conducted to implant the leads.  This may be 
beyond what is standard of care.  The risk associated with these additional images has been 
considered and determined to be minimal since the total radiation dose will be approximately 
the same as one CT scan of the abdomen.     
Study Risk Control Measures  
The following will be done to mitigate risks associated with the implanted system: 
• Investigators who are experienced with spinal cord stimulation implantation techniques 
will be utilized 
• Instructions will be given to the study participants to ensure they can properly use the 
patient programmer and recharger system 
• Subjects can turn off stimulation at any time during the study with the patient 
programmer or recharger 
• Periodic monitoring of the study participants 
• Written materials that contain precautions, warnings, and contraindications, as well as 
instructions on the use of the devices will be available and/or provided to the clinicians 
and subjects 
 
Since the efficacy measure in this study is intensity of pain in the back and legs, pain in these 
areas does not need to be reported as an adverse event unless it meets the definition of a serious 
adverse event. However, Investigators may, at their discretion, report any other pain-related 
adverse events during the study.   
 
C2.  Minimization of Risks 

 
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The study will use commercially available IntellisTM SCS system within the approved 
indications for use. The risks associated with the use of SCS systems have been well 
characterized and are minimal compared to the side effects associated with most surgical 
procedures or the use of many medications used to treat chronic pain conditions. Additionally, 
SCS therapy is reversible since the SCS device may be turned off and the SCS system may be 
explanted at any time for any reason.   
Study Investigators are experienced in the diagnosis and treatment of chronic pain, have proper 
surgical and clinical training and will take adequate steps to ensure subject safety throughout 
the entire study. 
Investigators and study personnel will receive product training to become familiar with the 
components of the IntellisTM SCS systems and their functions. They will also receive training 
on assessment tools and Good Clinical Practice (GCP) in the conduct of clinical trials with 
human participants.  
D.  Description of the Device 
D.1.  Each Important Component, Ingredient, and Property of the Device 
 
D.1.1.  Device System Overview 
The Intellis™ system is a totally implantable spinal cord stimulation system that is 
indicated to aid in the management of chronic intractable pain of the trunk and/or limbs. 
The system has been approved by the FDA and is available for commercial use. 
The Intellis system system consists of a rechargeable implantable neurostimulator (INS) 
with 16 output channels.  The INS is implanted in a subcutaneous pocket and is capable 
of stimulating the dorsal aspect of the spinal cord when used with one or two 8-contact 
percutaneous leads located in the epidural space.  The INS can be controlled by a Patient 
Programmer and/or a Clinician Programmer.   
Before permanent implantation, a trial phase of therapy lasting up to 10 days is required. 
Components of the system during trial include an External Neurostimulator (ENS) 
capable of delivering the same stimulation as the INS, and Stimulation Leads. Other 
components of the system include Clinician Programmer, Communicator, Patient 
Programmer, Extensions, Charger and charging system, and surgical accessories. 
 
D.1.2.  Device System Details  
 
 
 
Only FDA approved, commercially available components will be used for the study. 
 
D.1.2.1  Major Components 
Implantable Neurostimulator: Intellis neurostimulator (Model 97715, Medtronic, 
Minneapolis MN) will be used for the study. The INS is a multi-programmable, 
rechargeable device that delivers stimulation through one or two 8-electrode leads. The 
stimulation settings are stored in programs. A program is a specific combination of 
pulse width, rate, and amplitude settings acting on a specific electrode combination (up 
to 16 electrodes per program).  Each of the 16 electrodes in the leads can be set to be a 

 
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cathode, an anode, or to remain off.  The INS is powered by a Li-Ion rechargeable 
battery.  The INS is capable of stimulating the dorsal aspect of the spinal cord through 
the electrodes in the leads that are connected to the output terminals of the INS. The 
electrical pulses used for stimulation are generated using a single current source.  The 
INS is designed to produce charge-balanced, biphasic rectangular pulses.  
The battery is recharged using an external charger that uses transcutaneous RF energy 
transmission. The INS is capable of communicating with the Charger to control the 
recharging function.   
The INS communicates with the Clinician Programmer and Patient Programmer (also 
called Patient Remote Controller). Clinician Programmer is used to program the INS 
and the ENS. The Patient Programmer is used by the subject to control some of the 
therapy parameters, change therapy programs, and turn stimulation on and off. 
External Neurostimulator (ENS) for Trial Phase: The Medtronic Model 97725 
Wireless External Neurostimulator (ENS) is part of a neurostimulation system used for 
trial stimulation outside of the operating room. The ENS is powered by two standard 
alkaline AAA batteries. The ENS is connected to leads implanted in the subject. The 
subject uses the ENS during the Trial Phase to evaluate the effectiveness of SCS 
therapy prior to receiving a permanent implant. The ENS also communicates with the 
Clinician Programmer system and Patient Remote Controller, similar to the INS.  
Clinician Programmer System:  The Medtronic Model A710 Intellis™ clinician 
programmer application resides on a tablet and is intended to be used by healthcare 
professionals to program the ENS (Model 97725) and IntellisTM INS (Model 97715 and 
97716) for pain therapy. The Clinician Programmer requires the use of the 
Communicator (Model 8880T2) to communicate with the INS.  
Patient Programmer: The Patient Programmer (Model 97745), also called Patient 
Remote Controller, is a handheld unit able to communicate with the INS or ENS.  The 
Patient Programmer is powered by two standard AA alkaline batteries. The Patient 
Programmer is used by subjects to select the SCS therapy program to be applied, to 
turn on or off the INS or ENS, and to change some of therapy parameters such as 
stimulation amplitude.   
Charging System:  The Charging system (Model 97755) is used by the subject to 
transcutaneously charge the INS battery.  It is a portable device powered by a 
rechargeable battery and can be held in one hand. The charging system used in this 
study is a commercially available charging system manufactured by Medtronic 
(Minneapolis, MN) and fully compatible with the study INS. 
Stimulation Leads and Lead Extensions:  The study will use commercially available 
percutaneous eight-electrode leads manufactured by Medtronic (Minneapolis, MN) and 
compatible with the INS and ENS to be used in this study. The leads are positioned 
percutaneously in the epidural space of the subject and are used for delivering the 
stimulation field to the dorsal aspect of the spinal cord. The percutaneous leads are 
intended to be single use. Temporary or permanent percutaneous leads may be used 
during the Trial Phase of the study. The proximal end of these leads connect directly to 
the ENS. Permanent leads will be used during the Permanent Phase of the study. These 

 
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may be connected to a Lead Extension.  The leads or lead extensions are tunneled 
subcutaneously to connect to the INS. Commercially available lead extensions 
(Medtronic, Minneapolis, MN) compatible with the percutaneous leads and INS may 
be used in this study.  
 
D.1.2.2.  Surgical Accessories 
 
The surgical accessories that will be used in the study will be commercially available 
devices. 
Torque Wrench:  A commercially available Torque Wrench is used to tighten the 
screws that lock a percutaneous lead into the INS and/or a lead extension. It also tighten 
the screws that lock the lead extension into the INS when this is used. 
Lead anchors:  Lead anchors may be used to possibly prevent lead migration and/or 
lead strain. These are used to anchor the percutaneous leads to the supraspinous 
ligament or fascia.  Lead anchors used in this study are commercially available 
(Medtronic, Minneapolis, MN) and designed to slide freely over the lead length to the 
required fixation position. Surgical sutures are then tied around the anchor clamping 
the sleeve in place on the lead.   
Insertion Needle:  Percutaneous leads are implanted in the dorsal epidural space using 
insertion needles.  An insertion needle contains a cannula and stylet that facilitate 
access to the spinal canal for lead placement.  The insertion needle is a 14G epidural 
needle with a thin wall and a modified Touhy non-coring tip.  The cannula and stylet 
are designed to lock together and maintain the orientation of the tip of each component. 
The hub of the insertion needle has a standard luer fitting. 
Stylets:  Stylets are used to push and “steer” a percutaneous lead into the desired place 
within the epidural space.  The distal end of the stylet could be straight or curved.  The 
implanter is able to use either one in order to comfortably maneuver a percutaneous 
lead through the epidural space until it reaches the desired implant location. 
Tunneling Tool:  A Tunneling Tool is used to create a subcutaneous tunnel that directs 
the percutaneous leads or lead extensions from the midline incision to the leads from 
the INS implant site.  This is a single use tool.  
INS Template:  The INS Template is an aid to be used for the implanter intended for 
proper sizing of the INS pocket within each subject. 
INS Port Plug:  An INS Port Plug is used to seal the port of the INS that is not in use 
when only one percutaneous lead is implanted. 
Lead Blank:  A Lead Blank is an optional aid made out of flexible stainless steel that 
has an outer diameter similar in size to the percutaneous lead. A lead blank can be 
optionally used to clear a path for the introduction of a percutaneous lead into the 
epidural space.  
 
D.2.  Principle of Operation of the Device 

 
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Only commercially approved IntellisTM SCS system will be used according to its indications 
for use.  Spinal cord stimulation therapy for pain management has been used for more than four 
decades. Its efficacy and safety has been widely documented.  
 
D.3.  Labeling 
Instructions for Use:  The study devices will be used in accordance with IntellisTM Manual. 
 
D.4.  Any Anticipated Changes in the Device 
There are no anticipated changes at this time. 
 
E.  Administrative Procedures 
E.1.  Monitoring  
 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 
conduct of the trial is in compliance with the currently approved protocol/amendment(s), and 
with applicable regulatory requirement(s).   
E.1.1.  Study Clinical Monitor 
Stimgenics will assign a Clinical Monitor(s) in order to fulfill the required Sponsor and 
monitoring responsibilities according to the Study Monitoring Plan.  The Study 
Monitoring Plan describes in detail who will conduct the monitoring, at what frequency 
monitoring will be done, at what level of detail monitoring will be performed, the 
distribution of monitoring reports, and key monitoring activities and specifies the data to 
be reviewed over the course of the clinical study. The monitoring plan will facilitate 
compliance with Good Clinical Practices (GCP) and other relevant guidelines. The 
clinical study monitors will conduct monitoring visits in accordance with this plan.  
 
E.1.2. Monitoring Procedures 
Monitoring visits to the clinical investigational sites will be made on-site periodically and 
according to the monitoring Plan.  These visits will ensure that Investigators and their 
staff understand and accept their defined responsibilities, assess compliance with current 
GCP guidelines, evaluate clinical trial progress, assess the continued acceptability of the 
site facilities, evaluate compliance with this investigational plan, and verify the data 
entered on the eCRFs.  

 
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Investigators are to maintain, in an appropriate secure location, all source documents as 
required by the investigational plan. Source documents include signed informed consents. 
subject completed questionnaires, laboratory results, supporting medical records, and any 
applicable electronic files.  These source documents will be used by the Clinical Monitor 
at the scheduled monitoring visits to verify information entered into the EDC System. 
Clinical monitoring activities will include review and resolution of missing or 
inconsistent results to assure the accuracy of the reported data.  Where any discrepancies 
are noted, the Clinical Monitor will generate queries. Discrepancies will be resolved with 
the Investigator and/or an individual designated by the Investigator.  If data is incomplete, 
the Investigator will attempt to obtain the missing data.  The original source documents 
will remain stored in a secure location at the clinical sites as designated by the 
Investigator.   
The safety and welfare of study subjects will be ensured by following the appropriate 
GCP guidelines for informed consent, including proper documentation (Informed 
Consent Form) by following the investigational plan, and by reporting and following up 
adverse events as appropriate. 
The Clinical Monitor will summarize the evaluation and assessment of each monitoring 
visit in written reports. These reports will identify any issues with repeated data recording 
or reporting and will specify clear recommendations for resolution of noted deficiencies. 
The conduct and monitoring of the clinical investigation will be conducted in accordance 
with Stimgenics’ internal procedures.   
 
E.2.  Data Quality Assurance 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. The subject data will be entered into an electronic 
data capture system (EDC) system following the study visits. Hardcopies of the study visit 
worksheets will be provided for use as source document worksheets for recording data for each 
participant enrolled in the study.  All source documents should be completed in a neat, legible 
manner to ensure accurate interpretation of data. Data recorded in the electronic case report 
form (eCRF) should be consistent with the data recorded on the source documents. Data will 
be reviewed to identify inconsistent or missing data as well as potential adverse events.  Data 
discrepancies will be addressed by written communication or by telephone with the clinical site 
and/or during clinical site monitoring visits. Stimgenics and representatives of regulatory 
authorities are permitted to access study documents (e.g. investigational plan, eCRFs, medical 
records/files) as needed. All attempts will be made to preserve the privacy and confidentiality 
of subjects. 
 
E.3. Study Conduct 
The Investigator agrees that the study will be conducted according to this investigation plan, 
the principles of GCPs as outlined in the United States Code of Federal Regulations (CFR) - 21 
CFR Parts 50, 56 and 812, and the Sponsor internal standard operating procedures.  The 

 
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Investigator will conduct all aspects of the study in accordance with all Federal and local laws 
of pertinent regulatory authorities.  
The Investigator will assure correct implementation and conduct of the trial including those 
study related duties delegated to other appropriately qualified individuals and designated in the 
delegation of authority documentation.  The Investigator will assure that study staff cooperates 
with monitoring and audits, and will demonstrate due diligence in recruiting, screening, and 
retaining study subjects. 
The Investigator will also be responsible for filing an annual study progress report to the IRB 
as per IRB guidelines. The Investigator and/or Sponsor, as required by local regulations, are 
required to report in writing to the IRB, notice of completion, termination, or discontinuation 
of the study. If the study is discontinued for safety concerns, the Investigator and/or Sponsor 
will notify the IRB immediately.  
The Investigator is also responsible for recording and assessing the severity of Adverse Events. 
Investigators must report any severe adverse event (SAE) to the sponsor within 48 hours of 
knowledge of the event and to the IRB as per their regulations. 
The Investigator is also responsible for promptly reporting to the Sponsor any deviations and 
exceptions to this investigational plan and to the IRB per their requirements. 
 
E.4.  Informed Consent Materials 
Informed consent must be obtained from all subjects prior to study participation.  Informed 
consent will be obtained by the Investigator or an Investigator-designated healthcare 
professional as per GCP guidelines.  An informed consent form (ICF) will be provided to 
potential subjects for their private evaluation. If a subject consents to participate, the ICF must 
be signed by the subject or a legally authorized representative of the subject.  Study ICF must 
be approved by the IRB. Signed ICFs will be retained in the subject's study records at the 
clinical site. 
The ICF will be in compliance with the requirements set forth in 21 CFR 50, Protection of 
Human Subjects. 
 
E.5 Investigators and Institutions 
The clinical Investigators participating in this study will be chosen based on their qualifications 
and experience.   
 
E.6. Amendments and Deviations 
This investigational plan is to be followed by Investigators and all personnel involved in the 
clinical study.  Any changes to the study covered by this investigational plan must be 
documented on a formal investigational plan amendment prior to implementation in the study.  
Changes to the investigational plan may be initiated by Stimgenics or at the request of an 
Investigator.  A formal change to this study under this investigational plan cannot be initiated 

 
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by Investigator or clinical site personnel without Stimgenics’ approval, IRB approval, and the 
Investigator’s approval. 
Exception for Emergency Deviation:  An exception to the policy noted 
above is an emergency deviation to the investigational plan which may be 
initiated by the Investigator without prior approval from Stimgenics only 
in cases where a change is necessary to eliminate any immediate apparent 
hazard to subjects.  Emergency deviations must be reported to the Sponsor 
and the IRB no later than 24 hours following the emergency. 
Deviations from the investigational plan and study requirements (including GCP guidelines) 
will be reviewed by Stimgenics and will be evaluated on an ongoing basis. Appropriate 
corrective actions will be implemented as necessary. 
 
E.7. Additional Record and Reports 
This study will be registered on clinicaltrials.gov.  Sponsor/Investigator Records and Reports 
will be maintained and provided in accordance to 21 CFR 812.140 and 812.150.  No additional 
records or reports will be maintained. 
 
 
 

 
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F.  Appendices 
 
A. Informed Consent Form 
B. Case Report Forms 
 
 
 

 
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G.  References 
 
1 The Global Pain Therapeutics Market Analysis, R&D Pipelines and Competitive Landscape, 
Arrowhead Publishers, 2007, pp. 408. 
2 Institute of Medicine (US) Committee on Advancing Pain Research C, and Education. 
Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and 
Research. Washington (DC): National Academies Press (US), 2011, pp. 2. 
3 https://www.hhs.gov/opioids/about-the-epidemic/index.html 
4 Smits H, van Kleef M, Holsheimer J, et al. Experimental spinal cord stimulation and 
neuropathic pain: mechanism of action, technical aspects, and effectiveness. Pain Practice 2013; 
13:154-168.   
5 Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation of the 
spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic 
diseases: the neuromodulation appropriateness consensus committee. Neuromodulation 2014; 
17:515-550. 
6 Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation: avoidance 
and treatment of complications of neurostimulation therapies for the treatment of chronic pain. 
Neuromodulation. 2014; 17:571-597. 
7 Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain 
and failed back surgery syndrome: a systematic review and analysis of prognostic factors. Spine 
(Phila Pa 1976) 2005; 30:152-160. 
8 Kapural L, Yu C, Doust MW, et al. Novel 10-kHz high-frequency therapy (HF10 Therapy) is 
superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back 
and leg Pain: The SENZA-RCT randomized controlled trial. Anesthesiology 2015; 123:851-860.