Comparison of Differential Target Multiplexed Spinal Cord Stimulation (DTM™ SCS) Therapy Combined With CMM to CMM Alone in the Treatment of Intractable Back Pain Subjects Without Previous History of Lumbar Surgery
Phase: NA
Conditions: Pain, Intractable, Pain, Chronic
Sponsor: MedtronicNeuro

Comparison of DTM™ SCS Therapy Combined with CMM to CMM Alone in the Treatment of 
Intractable Back Pain Subjects without previous history of Lumbar Spine Surgery 
 
Clinical Investigational Plan, Revision B, 21 Aug 2020 
 
NCT06442410 

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CLINICAL INVESTIGATIONAL PLAN 
Comparison of DTMTM SCS Therapy Combined with CMM to CMM Alone in the Treatment 
of Intractable Back Pain Subjects without previous history of Lumbar Spine Surgery 
Protocol Number: 
 
 
DTM-INT-2020PM2 
 
Study Reference: 
 
 
EU RCT  DTMTM SCS vs CMM 
 
Sponsor: 
 
 
 
SGX International 
2406 E. Empire St.  
Bloomington, IL 61704 
 
United States of America 
 
Study Responsibility:  
 
 
 
 
 
 
 
 
 
 
 
 
SGX International 
 
Date of Issue:  
 
 
21 Aug 2020  
 
Revision: 
 
 
 
B 
 
Revision History: 
 
 
Revision 
Description 
Date 
A 
Initial Release of Clinical Investigational Plan 
 01 Apr 2020 

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B 
Clarifications:  
- Section 3.2: Inclusion criterion nr. 2 
- Section B.4 & B.6.16: Definition CMM 
- Section B.6.16: CMM treatment at the 1 month visit.  
- Section B.6.19: Medication usage 
Corrections:  
- Section B.5.5.1: test basis statistical power 
- Section B.7.1: definition modified intent-to-treat 
- Section B.9.2: corrections statistical analyses 
Request Ethics Committee (Spain):  
- Section B.9.1: EU GDPR reference 
Administrative changes:  
- Section B.9.1: Added text regarding remote data 
collection (due to a formatting issue with Rev A this text 
was accidently removed) 
- Section B.9.1: Table 1a & 1b (corrections in the Schedules 
of Study Activities)  
21-Aug-2020 

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Study Synopsis 
Study Title 
Comparison of Differential Target Multiplexed Spinal Cord Stimulation 
(DTMTM SCS) Therapy Combined with CMM to CMM Alone in the Treatment 
of Intractable Back Pain Subjects without previous history of Lumbar Surgery 
Protocol 
Number 
DTM-INT-2020PM2 
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 document the safety, clinical 
effectiveness and health economic analytics of DTMTM SCS programming 
delivered through the IntellisTM neurostimulator in subjects with chronic, 
intractable pain of the trunk with or without lower limb pain, including 
unilateral or bilateral pain without prior history of spine surgery and refractory 
to conservative treatment and are not candidates for lumbar spinal surgery. 
Study 
Design 
This is a post-market, open-label, prospective, randomized, controlled, multi-
center study comparing DTMTM SCS programming approach, delivered through 
the CE marked IntellisTM neurostimulator, to Conventional Medical 
Management (CMM). 
 
Subjects meeting study entrance criteria will be randomized in a 1:1 ratio to one 
of two study treatment groups: 
• Test treatment group with DTMTM SCS programming approach with 
CMM 
• Control treatment group with CMM alone 
 
Data at follow-up visits will be compared between the two treatment groups, 
and compared to baseline assessments collected at the beginning of the study. 
 
There is an optional two-way crossover to the other treatment group available 
for all subjects who remain in the study at the 6-months visit. 
Study Size 
Up to 300 subjects may be enrolled at up to 15 clinical sites in Europe in order 
to include an estimated 150 subjects to the point of randomization. 
 
This would allow minimum 100 subjects (50% in each treatment arm) to 
complete the 6-month primary endpoint. 
Study 
Duration 
The expected total duration of this study is approximately 44 months.   
Enrollment of subjects is expected to last 18 months.  
Subjects who have received the permanent implant will be followed up for 
approximately 26 months. This consists of Baseline assessments, up to 7 to 30 
days (depending on the practice) of trial stimulation, and 24 months of 
treatment following implantation and activation of the device or 24 months of 
study visits for those in the CMM arm.  
Study 
Objective 
The primary objective of this study is to evaluate the effectiveness of  DTMTM 
SCS  in reducing back pain as compared to CMM for the treatment of 
intractable chronic low back pain. 

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Other objectives of this study are to document the safety, clinical effectiveness 
and health economic analytics of  DTMTM SCS in subjects with intractable 
chronic low back pain. 
Inclusion 
Criteria 
A subject must MEET ALL of the following inclusion criteria: 
1. Be a candidate for SCS system (trial and implant)  
2. Have been diagnosed with chronic, refractory axial low back pain with or 
without lower limb pain, with a neuropathic component as assessed by the 
investigator, 6 months refractory to conventional therapy and are not 
eligible for spine surgery (e.g., lumbar fusion, discectomy, laminectomy, 
laminotomy) at the time of enrollment 
3. Has an average back pain intensity ≥ 6.0 cm on the 10.0 cm Visual Analog 
Scale (VAS) at the time of enrollment  
4. 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. 
5. Be willing and capable of subjective evaluation, read and understand written 
questionnaires, and read, understand and sign the written inform consent. 
6. Be 18 years of age or older at the time of enrollment 
7. Be on a stable pain medication regimen, as determined by the study 
investigator, for at least 30 days prior to enrolling in this study 
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. Had previous lumbar spinal surgery (e.g., lumbar fusion, discectomy, 
laminectomy, laminotomy)  
2. Has a medical, anatomical, and/or psychosocial condition that is 
contraindicated for commercially available IntellisTM SCS systems as 
determined by the Investigator 
3. Has a diagnosed back condition with inflammatory causes of back pain 
(e.g., onset of severe pain with activity), serious spinal pathology and/or 
neurological disorders as determined by the investigator 
4. Be concurrently participating in another clinical study 
5. Has an existing active implanted device such as a pacemaker, another SCS 
unit, peripheral nerve stimulator, and/or drug delivery pump, etc. 
6. 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 
7. Has mechanical spine instability as determined by the Investigator 
8. Has undergone, within 30 days prior to enrollment, an interventional 
procedure to treat back and/or leg pain, which is providing significant pain 
relief  
9. Has unresolved major issues of secondary gain (e.g., social, financial, legal), 
as determined by the investigator 

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10. Be involved in an injury claim under current litigation or has a pending or 
approved worker’s compensation claim 
11. 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 6 months (superiority analysis).  Subjects who do not have a 
successful Trial Phase are considered failures (non-responders) toward the 
primary endpoint. 
Secondary 
Endpoints 
& 
Additional 
Measures 
Secondary endpoints of this study are to further document the safety, clinical 
effectiveness and  health economic analytics of the  DTMTM SCS delivered 
through IntellisTM system when compared to CMM alone for the treatment of 
chronic pain of the back and limbs.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
CLINICAL INVESTIGATIONAL PLAN ..................................................................................1 
Study Synopsis ................................................................................................................................3 
A.  Purpose ......................................................................................................................................9 
A.1.  Study Device .....................................................................................................................9 
A.2.  Purpose of the Investigation ..............................................................................................9 
A.3.  Study Size .........................................................................................................................9 
A.4.  Duration of the Investigation ..........................................................................................10 
B.  Protocol ...................................................................................................................................10 
B.1.  Rationale for Study..........................................................................................................10 
B.2.  Study Objectives .............................................................................................................12 
B.3.  Selection of Study Population .........................................................................................12 
B.3.1.  Study Population ..............................................................................................12 
B.3.2.  Inclusion Criteria ..............................................................................................12 
B.3.3.  Exclusion Criteria .............................................................................................13 
B.4.  Treatment Groups ............................................................................................................14 
B.5.  Study Design ...................................................................................................................15 
B.5.1.  Overall Design ..................................................................................................15 
B.5.2.  Bias Minimization ............................................................................................15 
B.5.3.  Comparison Groups..........................................................................................15 
B.5.4.  Blinding ............................................................................................................15 
B.5.5.  Sample Size ......................................................................................................16 
B.5.5.1 Sample size rationale and statistical power .....................................................16 
B.5.5.2 Overall Sample Size and Enrollment ..............................................................16 
B.5.6.  Study Duration .................................................................................................17 
B.5.7.  Interim Administrative Analyses .....................................................................17 
B.6.  Enrollment, Assessments, Randomization, and Clinical Procedure ...............................17 
B.6.1.  Summary of Study Protocol .............................................................................17 
B.6.2.  Enrollment/Entry Criteria Evaluation ..............................................................21 
B.6.3.  Baseline ............................................................................................................21 
B.6.4.  Randomization .................................................................................................21 
B.6.5.  Test Arm:  DTMTM SCS  Trial Phase ..............................................................22 
B.6.6.  Test Arm: End of Trial Assessment .................................................................22 
B.6.7.  Test Arm: Permanent Device Implant (0-90 days from end of successful Trial 
Phase) 
23 
B.6.8.  Test Arm: Device Activation (0-14 days following Permanent Implant) ........23 
B.6.9.  Test Arm: 1 Month After Device Activation (± 15 days) ................................23 
B.6.10.  Test Arm: 3 Months After Device Activation (± 21 days) ............................24 
B.6.11.  Test Arm: 6 Months After Device Activation (± 31 days) ............................24 
B.6.12.  Test Arm: 9 Months After Device Activation (± 31 days) ............................24 
B.6.13. Test Arm: 12 Months After Device Activation (± 45 days) ...........................24 

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B.6.14.  Test Arm: 18 Months After Device Activation (± 45 days) ..........................25 
B.6.15. Test Arm: 24 Months After Device Activation (± 60 days) ...........................25 
B.6.16 Control Arm: CMM .........................................................................................26 
B.6.17.  Unscheduled Visits .........................................................................................28 
B.6.18.  Telephone Calls ..............................................................................................28 
B.6.19.  Other Assessments and Information ..............................................................28 
B.6.20.  Device Explant ...............................................................................................29 
B.6.21.  Early Subject Withdrawal ..............................................................................29 
B.6.22.  Study Completion ...........................................................................................30 
B.6.23.  Study Suspension and Termination ................................................................30 
B.7.  Study Endpoints ..............................................................................................................31 
B.7.1.  Definition of Analysis Populations ..................................................................31 
B.7.2.  Effectiveness Assessment Definitions .............................................................31 
B.7.3.  Primary Endpoint .............................................................................................31 
B.7.4.  Secondary Endpoints ........................................................................................32 
 
B.7.6.  Safety ................................................................................................................33 
B.8.  Evaluation Criteria ..........................................................................................................36 
B.8.1.  Effectiveness ....................................................................................................36 
B.8.2. Safety Measurements ........................................................................................37 
B.8.3. Health Economic Measures ...............................................................................37 
B.8.2.  Definition of Success .......................................................................................37 
B.9.  Data Collection and Analysis ..........................................................................................38 
B.9.1.  Data Collection .................................................................................................38 
B.9.2.  Statistical Analysis ...........................................................................................42 
B.9.2.1 Primary Analyses ............................................................................................42 
B.9.2.2 Secondary Analyses ........................................................................................42 
 
B.9.2.4 Handling of Missing Data ...............................................................................44 
C.  Risk Analysis ..........................................................................................................................45 
C.1.  Description and Analysis of All Increased Risks to Subjects .........................................45 
C2.  Minimization of Risks ......................................................................................................47 
D.  Description of the Device .......................................................................................................48 
D.1.  Each Important Component, Ingredient, and Property of the Device .............................48 
D.1.1.  Device System Overview .................................................................................48 
D.1.2.  Device System Details .....................................................................................48 
D.1.2.1  Major Components .........................................................................................48 
D.1.2.2.  Surgical Accessories .....................................................................................50 

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D.2.  Principle of Operation of the Device ..............................................................................50 
D.3.  Labeling ..........................................................................................................................51 
D.4.  Any Anticipated Changes in the Device .........................................................................51 
D.5.  Device Accountability.....................................................................................................51 
E. Administrative Procedures .....................................................................................................51 
E.1.  Monitoring .......................................................................................................................51 
E.1.1.  Study Clinical Monitor .....................................................................................51 
E.1.2. Monitoring Procedures ......................................................................................51 
E.2.  Data Quality Assurance ...................................................................................................52 
E.3. Study Conduct ..................................................................................................................52 
E.4.  Informed Consent Materials ............................................................................................53 
E.5 Investigators and Institutions .............................................................................................53 
E.6. Amendments and Deviations ............................................................................................53 
E.7. Additional Record and Reports ........................................................................................54 
E. 8 Publication Policy .............................................................................................................54 
F. Appendices ...............................................................................................................................55 
F. 1 Appendix I – Clinical Investigation Plan Signature Page ....................................55 
F. 2 Appendix II – List of Abbreviations .....................................................................56 
G.  References ...............................................................................................................................57 
 
 
 

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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, stable intractable peripheral vascular disease, or stable 
intractable angina pectoris.  It is designed to deliver electrical stimulation to the spinal cord 
using an array of electrodes (also called leads) placed in the dorsal epidural space.  The study 
will use the commercially available IntellisTM neurostimulator and compatible SCS system 
components from Medtronic in accordance to the approved CE mark labeling (i.e. on-label use). 
Section D of this Investigational Plan provides a detailed description of the IntellisTM 
neurostimulator. The study devices will be used in accordance with the IntellisTM Manual. 
 
A.2.  Purpose of the Investigation 
The purpose of this post-market study using the CE marked IntellisTM neurostimulator is to 
evaluate the effects of Differential Target Multiplexed SCS (DTMTM SCS) programs in subjects 
with chronic, intractable pain of the trunk with or without lower limb pain.  The  DTMTM SCS 
programming approach uses on-label SCS programming parameters
 
 
This therapy is CE-marked, commercially available and the 
related procedures (trial and permanent implant) are part of the standard practice and are not 
investigational. The pain symptoms of the study population are commonly associated with 
degenerative spine conditions such as Degenerative Disk Disease (DDD) or herniated 
intervertebral disks, which are refractory to conservative treatments,  and do not indicate the 
need for surgical interventions of the lumbar spine. This study is a post-market, open-label, 
multi-center, prospective, randomized, controlled clinical trial that evaluates the treatment 
outcomes resulting from the  DTMTM SCS programming approach with Conventional Medical 
Management (CMM) versus CMM alone. The DTMTM SCS programming approach with CMM 
will be discussed more in section B.1 of this Investigational Plan. 
 
A.3.  Study Size 
Up to 300 subjects may be enrolled at up to 15 clinical sites in Europe in order to include an 
estimated 150 subjects to the point of randomization. This would allow a minimum of 100 
subjects (50% in each treatment arm) to complete the 6-month primary endpoint. Sample size 
estimates are discussed further in section B.5.5 of this Investigational Plan.  
 
 
 
 
 

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A.4.  Duration of the Investigation 
The expected total duration of this study is approximately 44 months.  Enrollment of subjects 
is expected to last 18 months. Subjects that have received the permanent implant will be 
followed up for approximately 26 months. This consists of Baseline assessments, duration of 
trial stimulation (up to 7 to 30 days depending on the practice), implantation and activation of 
the device and 24 months of study visits for those in the CMM arm.  
 
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 (CMM), including medication and physical therapy, is 
often not adequate for treating chronic pain. Medication therapy based on opioids may also 
lead to addiction. Indeed, extensive use of opioid medications in the United States has led to 
the declaration of an epidemic crisis3. When these treatments fail to provide pain relief, 
imaging is performed to assess candidacy for back surgery4. However, surgery is only 
indicated for those patients with mechanical instability or pinched nerves5. For the many 
patients for whom imaging does not clearly show a cause of chronic back pain, or for the 
patients that have confounding medical issues precluding an invasive surgical procedure, there 
are few alternative treatment options6. Furthermore, surgical interventions have also failed to 
remediate severe cases of neuropathies and intractable back pain for many patients. Yoshihara 
et al. evaluated the surgical trends for lumbar degenerative disc disease in the US from 2000 
to 20097. They reported a 2.4-fold population-adjusted increase. Bae et al. reported an increase 
in the number of lumbar surgical fusion for spinal stenosis from 21.5% to 31.2% between 2004 
and 20098. Re-operation rate for disc herniation and spinal stenosis varied between 10 to 23%9. 
Overall, 40% of patients developed post-laminectomy syndrome or failed back surgery 
syndrome, requiring further treatment, with an estimated incidence of 80,000 cases per year10. 
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) system11,12,13,14. Taylor et al showed the cost effectiveness 
of SCS versus surgery and other interventions at $7,058 USD per quality adjusted life year15.  
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.   

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The Differential Target Multiplexed SCS (DTMTM SCS) programming approach 
 
 
 
 This can be done with programming parameters that are 
currently available on the IntellisTM neurostimulator device. 
In a given program group,  DTMTM SCS will provide programs 
 
  
 
 
 
 
 
 
 
   
There is an ongoing post-market, open-label, prospective, randomized controlled study 
(NCT03606187) evaluating the  DTMTM SCS programming approach versus the Conventional 
one. The study includes more than 100 subjects randomized in 12 sites in the U.S. At the 3-
month primary endpoint, the responder rate (percentage of subjects with ≥50% pain relief) for  
DTMTM SCS programming was 80% vs 51% for the active control arm. Thus, the study met 
the primary objective for non-inferiority. A secondary objective of superiority of  DTMTM SCS 
was also met for the primary outcome. In addition, the mean percent of back pain relief relative 
compared to baseline at the 3-months follow up for  DTMTM SCS was 74% vs. 46% for 
conventional programming.   
Thus, the ongoing study has shown that  DTMTM SCS is more effective than conventional SCS 
at the 3-month primary endpoint of the study. Results also show that  DTMTM SCS shows a 
risk profile in line with that of the widely documented profile for conventional SCS. Therefore,  
DTMTM SCS programming approach offers an alternative programming approach to SCS that 
might help thousands of chronic pain sufferers make substantial improvements in pain relief, 
reduction in disabilities, and reduce the likelihood of uncomfortable paresthesia. 
A multicenter feasibility study (NCT03110601) has also been completed in which DTMTM 
SCS programming approach was evaluated during the required period for trialing SCS therapy. 
In this acute study, 20 subjects completed a trial with  DTMTM SCS and Conventional SCS 
programming approaches. In terms of back pain relief, the DTMTM SCS programming 
approach provided a mean of 68% pain relief and the Conventional SCS programming 
approach provided a mean of 43% pain relief, which translates to  DTMTM SCS achieving 25% 
greater reduction than Conventional SCS.  Notably with  DTMTM SCS, 80% of subjects 
experienced 50% or better back pain relief, and 85% of the subjects preferred therapy received 
through  the DTMTM SCS programming approach. The safety results were in line with 
expectations of previous SCS studies and the adverse events 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 trials and was not 
related to either programming approach. There were no unanticipated adverse events. 

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The current study is a post-market, open-label, prospective, randomized, controlled multi-
center study that will evaluate  DTMTM SCS programming with CMM in comparison to CMM 
alone for chronic back pain sufferers with or without leg pain.  This scientifically sound study 
will provide more information on safety, efficacy and health economic analytics for  the   
DTMTM SCS  programming approach. 
 
B.2.  Study Objectives 
The primary objective of this study is to evaluate the clinical effectiveness of  DTMTM SCS 
with CMM in reducing back pain as compared to CMM alone for the treatment of intractable 
chronic back pain. 
The secondary objectives of this study are to further document the safety, clinical effectiveness 
and health economic analytics of the  DTMTM SCS delivered through IntellisTM system when 
compared to CMM alone, for the treatment of chronic pain of the trunk and limbs.   
 
B.3.  Selection of Study Population 
 
B.3.1.  Study Population  
The intended study population are individuals suffering from chronic, intractable pain of 
the back and/or limbs who are not considered candidates for spine surgery 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)  
2. Have been diagnosed with chronic, refractory axial low back pain with or without 
lower limb pain, with a neuropathic component as assessed by the investigator, 6 
months refractory to conventional therapy and are not eligible for spine surgery 
(e.g., lumbar fusion, discectomy, laminectomy, laminotomy) at the time of 
enrollment  
3. Has an average back pain intensity ≥ 6.0 cm on the 10.0 cm Visual Analog Scale 
(VAS) at the time of enrollment 
4. 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. 
5. Be willing and capable of subjective evaluation, read and understand written 
questionnaires, and read, understand and sign the written inform consent  
6. Be 18 years of age or older at the time of enrollment 
7. Be on a stable pain medication regime, as determined by the study investigator, for 
at least 30 days prior to enrolling in this study 
8. Be willing and able to comply with study-related requirements, procedures, and 
visits 

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B.3.3.  Exclusion Criteria 
In order to participate in the study, a subject must NOT MEET ANY of the following 
exclusion criteria: 
1. Had a previous spinal surgery (e.g., lumbar fusion, discectomy, laminectomy, 
laminotomy) 
2. Has a medical, anatomical, and/or psychosocial condition that is contraindicated 
for commercially available IntellisTM SCS systems as determined by the 
Investigator 
3. Has a diagnosed back condition with inflammatory causes of back pain (e.g., 
onset of severe pain with activity), serious spinal pathology and/or neurological 
disorders as determined by the Investigator 
4. Be concurrently participating in another clinical study 
5. Has an existing active implanted device such as a pacemaker, another SCS unit, 
peripheral nerve stimulator, and/or drug delivery pump, etc. 
6. 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 
7. Has mechanical spine instability as determined by the Investigator 
8. 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  
9. Has unresolved major issues of secondary gain (e.g., social, financial, legal), as 
determined by the investigator 
10. Be involved in an injury claim under current litigation or has a pending or 
approved worker’s compensation claim 
11. 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.) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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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: 
Control treatment group: Conventional Medical Management (CMM) 
• The choice of appropriate Conventional Medical Management will be made by the 
Investigator as determined to be the best standard of care for each individual 
subject i.e. optimized individual conventional therapy. These treatments would be 
generally consistent with the American College of Physicians and the American Pain 
Society 
Guidelines 
as 
published 
in 
the 
Annals 
of 
Internal 
Medicine 
(http://annals.org/article.aspx?articleid=736814) and European/UK guidelines1,2,3. The 
CMM treatment can be modified at any moment by the investigators based on their 
clinical evaluation and local standard of care. They may also consists of one or more 
of the following treatments: 
• Medications: Over-the-counter analgesic medications, opioid medications, 
nonsterioidal anti-inflammatory drugs (NSAIDs), anticonvulsants, 
antidepressants, topical analgesics 
• Combined physical and psychological management (CPPM) 
• Physical therapy 
• Back rehabilitation program 
• Spinal manipulation and spinal mobilization 
• Traction 
• Acupuncture 
• Cognitive behavioral therapy (CBT) 
• Biofeedback 
• Nerve blocks 
• Radio frequency ablation 
• Epidural steroid injections 
• Transcutaneous electrical nerve stimulation (TENS) 
• Intradiscal electrothermal therapy (IDET) 
• Nucleoplasty, also called plasma disc decompression (PDD) or similar 
Test treatment group:  DTMTM SCS programming approach with CMM 
• Along with the appropriate CMM treatment made by the Investigator, the subject 
will be trialed and implanted with an IntellisTM neurostimulator system using  
DTMTM SCS programming parameters. 
 
 
 
1 Clinical guidelines for the management of low back pain in primary care: an international comparison; Spine. 
26(22):2504-2513, November 15th, 2001. Koes et al 
2 Clinical guidelines for the management of non-specific low back pain in primary care: an updated overview; 
European Spine Journal 27, 2791-2803(2018).Oliveira et al 
3 Low back pain and sciatica in over 16s: assessment and management. NICE guideline. Published 30 November 
2016. www.nice.org.uk/guidance/ng59 

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B.5.  Study Design 
 
B.5.1.  Overall Design 
This is a post-market, open-label, multi-center, prospective, randomized, controlled study 
to evaluate  DTMTM SCS with CMM in comparison to CMM alone, in subjects with 
chronic, intractable back pain, who have not received lumbar spine surgery and are not 
candidates for back surgery.  Data at follow-up visits will be compared between the two 
treatment groups, and compared 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 and will be performed 
by an electronic system. Regular follow-up visits and phone calls from the site personnel 
either as part of the study protocol or routine clinical practice should minimize attrition. 
 
B.5.3.  Comparison Groups 
Both groups in the study are treatment groups. Treatment outcomes from subjects in the  
DTMTM SCS with CMM group (test treatment) will be compared to those of the CMM 
alone group (control treatment).   
 
B.5.4.  Blinding 
Due to the nature of the treatment groups, comparing an implantable medical device with 
conventional medical management that may involve multiple different treatments, it is not 
feasible to blind the subjects, implanting physicians or the clinical site personnel to the 
group assignments. The assessment of treatments 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 which treatment arm 

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they are assigned to. In order to minimize potential assessment bias, the subjects will 
receive the standard instructions for completing the questionnaires. 
 
 
B.5.5.  Sample Size 
Primary Endpoint Assessment occurs at the follow up visit 6 months after Device 
Activation for subjects randomized in the  DTMTM SCS with CMM group, or 6 months 
after randomization for those in the CMM alone group.  Based on the primary endpoint 
requirement, the estimated sample size of this study is 100 total subjects (approximately 
50 subjects in the  DTMTM SCS with CMM group and approximately 50 subjects in CMM 
alone group) who have passed screening requirements and have been randomized.   
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 150 subjects to the point of randomization, up to 300 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 superiority of the test group to the control group.  
Established methods were followed in determining the superiority criteria and the 
related sample size estimate 
• Test basis: Pearson Chi-square binomial test for superiority 
• Estimated responder rate of 60% in the test group and 30% in the control 
group 
• Significance level, alpha, of 0.05 two-sided 
• Randomization:  1:1 
• A sample size of 50 subjects in each group will result in greater than 85% 
power for the study 
Based on these assumptions, a minimum of 50 randomized 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 33% 
for subjects that do not complete the Trial Phase, and subjects that exit study before 
the 6-month primary endpoint visit, approximately 150 subjects would need to be 
randomized.    

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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 300 subjects would need to be enrolled in the study. 
 
B.5.6.  Study Duration 
This study is expected to last approximately 44 months.  Enrollment of subjects is expected 
to last 18 months. Subjects who are expected to complete the study will commit to it for 
approximately 26 months. This consists of Baseline assessments, trial stimulation phase 
for those randomized to  DTMTM SCS, and 24 months of treatment following implantation 
and activation of the device or 24 months after randomization for those subjects 
randomized to CMM alone.  
 
B.5.7.  Interim Administrative Analyses  
 
In order to monitor data on patient safety and to help ensure accuracy of data collection, 
administrative analyses may be performed.  The results of the analyses will not be widely 
distributed, and access will be limited to those persons on a “need to know” basis.    
Administrative analyses 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 also prevents operational bias due to knowledge of interim results. 
 
B.6.  Enrollment, Assessments, Randomization, and Clinical Procedure 
Enrollment of subjects will occur at the clinical sites after Ethics Committee (EC) 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.  Notice of availability of the study 
may be used for recruitment purposes, upon approval of the patient recruitment materials 
by the study EC(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. Baseline assessments will include measures for pain intensity, 

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use of medication, extent of disability, health care utilization, work status and quality of 
life. 
Following completion of the baseline assessment, study subjects will be randomized in a 
1:1 ratio to either the  DTMTM SCS programming group + CMM or the CMM alone group.  
 
 Subjects randomized in the test group (DTMTM SCS with CMM) will be 
scheduled for the trial stimulation phase, lasting approximately up to 30 days based 
on typical clinical practice of the site, to determine the subject’s response to  
DTMTM SCS. Temporary or permanent leads and an external neurostimulator 
(ENS) will be used during this Trial Phase. Subjects will evaluate the therapy based 
on pain intensity under optimal DTMTM SCS parameters. Those who have a 
"successful Trial Phase" (defined as a 50% or greater pain reduction from Baseline 
in their back pain) will proceed to receive a permanent implant of leads and the 
internal neurostimulator (INS) and will undergo up to 24 months of stimulation 
delivery with assessments at 1, 3, 6, 9, 12, 18 and 24 months after the activation of 
the therapy. The implanted INS will be activated within 14 days after surgical 
procedure and DTMTM SCS therapy will be delivered for the next 24 months. 
Activation of the device marks the initial time point for effectiveness evaluation of 
the test study therapy after implantation. If needed, the investigator may attempt 
other SCS programming parameters available on IntellisTM neurostimulator to 
provide pain relief. If other parameters are effective, the parameters should be noted 
and analyzed. Assessments for pain intensity, use of medication and adverse events 
will be made at 1 month following Device Activation. At 3, 6, 9, 12, 18 and 24 
months after Device Activation, subjects will be assessed for pain intensity, adverse 
events, extent of disability, use of medication, quality of life , health care utilization, 
Patient Global Impression of Change, and subject satisfaction. In addition, work 
status will be evaluated at 6, 12 and 24 months. 
 Subjects randomized in the control group (CMM alone) will follow the best 
standard of care under CMM as prescribed by the  Investigator i.e. optimized 
individual conventional therapy (see Section B.6.16). Randomization into the 
control group marks the initial time point for evaluation of the control study 
therapy. Subjects in the control group will also undergo up to 24 months of CMM 
with the same assessments as the test group at 1, 3, 6, 9, 12, 18 and 24 months after 
randomization.  
 Crossover: Subjects randomized to either treatment group will have the possibility 
to crossover to the alternative treatment arm after the 6-month visit, if they meet all 
of the following criteria: 
• < 50% back pain relief from baseline;  
• Documented subject dissatisfaction with the treatment (“dissatisfied” or “very 
dissatisfied” on subject satisfaction measure); 
• Investigator agreement with crossover 
Crossover from  DTMTM SCS + CMM to CMM: will occur following completion 
of the 6 month follow-up visit. If the subject and investigator believe that the  
DTMTM SCS + CMM treatment has not generated sufficient pain relief to warrant 

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continued treatment, then the subject will be provided with the option to crossover 
to the CMM group. If all SCS programming attempts fail, then DTMTM SCS 
therapy will be switched off and the subject will continue with their CMM treatment 
and will visit the clinic at the 9, 12 and 18 month visits (approximately a total of 18 
months follow-up in the study i.e. 6 months  DTMTM SCS and 12 months CMM). 
The subjects will be indicated as a ‘crossover to CMM’. The subject can exit the 
study at any time to try other therapies not falling under CMM or not available in 
this study. This will be based on the investigator’s assessment and will be 
documented in the CRF and source notes. 
Crossover from CMM to  DTMTM SCS + CMM: will occur following completion 
of the 6 month follow-up visit. If the subject and investigator believe that the CMM 
treatment has not generated sufficient pain relief to warrant continued treatment, 
then the subject will be provided with the option to crossover to the  DTMTM SCS 
therapy group. The subject will be indicated as a ‘crossover to  DTMTM SCS’. The 
subject will then undergo a trial phase with  DTMTM SCS therapy. If the trial phase 
is successful (i.e. at least 50% pain relief compared to the baseline VAS score), the 
subject will proceed to a permanent device implantation. Following their device 
activation, they will attend visits starting at 1 month after device activation and 
continue the study visits until 12 months post-device activation (approximately a 
total of 18 months follow-up in the study i.e. 6 months CMM and 12 months  
DTMTM SCS). 
 
Figure 1 summarizes the sequence of study-related assessments, procedures, and visits. 
 
 

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Figure 1.  Study Flowchart 
 
 
 

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B.6.2.  Enrollment/Entry Criteria Evaluation 
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.  
The eligibility of subjects who have consented 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. Pregnancy tests will be conducted for 
participants of child bearing potential; pregnant women will not be allowed to participate 
(see also Section B.6.6 - Note).  Subjects with confirmed eligibility will proceed to Baseline 
assessment, while subjects who do not will be discontinued from the study.   
It is recommended that all above assessments are performed in 1 day; a 14 day window to 
collect the appropriate data for eligibility assessment is allowed.  
 
B.6.3.  Baseline 
Before a subject is randomized, a subject will be requested to fill out standard 
questionnaires that will assess 
 use of medications, healthcare 
utilization, 
  The medical and surgical history of the subject 
will be collected.  
Only applicable for the DTMTM SCS arm: Pre-operative assessments will follow the 
standard of care for SCS therapy and be determined by the site Investigator.  
Note: the enrollment, entry criteria evaluation and baseline visit might be combined in one 
visit, if all enrollment and entry criteria fulfilled at time of the baseline visit.  
 
B.6.4.  Randomization 
Subsequent to completing Baseline assessments, qualifying subjects will be randomly 
assigned to either one of the two study treatment groups:  DTMTM SCS programming with 
CMM or CMM alone. Randomization will be stratified by gender and whether the subject 
has leg pain or no leg pain at Baseline. Randomization will be done at each study site by 
randomly permuted blocks. Randomization assignments will be computer-generated and 
allocated via the Electronic Data Capturing (EDC) system. 
 
 
 
 

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B.6.5.  Test Arm:  DTMTM SCS  Trial Phase 
Subjects will undergo a Trial Phase with  DTMTM SCS programming. The Trial Phase will 
last up to 30 days depending on the typical clinical practice of the site. As part of the 
standard SCS practice, 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. Stimulation will be delivered from an external neurostimulator 
(ENS).   
As per standard SCS practice 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. 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
*Note: Depending on the standard of care for SCS practice at the participating site and if 
the time window is ≥28 days between criteria evaluation and trial implant, for participants 
of child bearing potential a pregnancy test will be repeated at the pre-assessment for the 
trial implant.  
 
B.6.6.  Test Arm: 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 will  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 50% or greater pain reduction 
from Baseline in their back pain) will proceed to permanent implantation of the SCS system 
to evaluate  DTMTM SCS therapy, and permanent implantation of the IntellisTM SCS system 
will be scheduled. A threshold of 50% 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).  

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Data from subjects who did not achieve 50% or greater pain reduction in back pain will 
not receive permanent implantation and will be carried forward toward the primary 
endpoint. These subjects will have the leads explanted and will exit the study. Following 
this exit, 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. 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.6.7.  Test Arm: Permanent Device Implant (0-90 days from end of successful Trial 
Phase) 
As described in section B.6.6, subjects who underwent a successful trial of DTMTM SCS 
programming and who agreed to continue into the next stage of the study will proceed to 
permanent implantation stage.  
As per standard SCS practice, 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. As per standard practice anterior-posterior (AP) and lateral X-ray imaging will 
be obtained.  Standard practice of the 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.6.8.  Test Arm: 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 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.6.9.  Test Arm: 1 Month After Device Activation (± 15 days) 
Subjects will visit the study site where they will be assessed for pain intensity.  
Programming adjustments may be made, as needed. As per standard practice, anterior-
posterior (AP) and lateral X-ray imaging may be done if significant lead migration is 
suspected. Subjects will be assessed for adverse events, healthcare utilization and 
medication usage.  
 
 
 

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B.6.10.  Test Arm: 3 Months After Device Activation (± 21 days) 
Subjects will visit the study site where they will be assessed for pain intensity,
 
 
Programming adjustments may be made, as needed. As per standard practice, 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, healthcare utilization 
and medication usage.  
 
B.6.11.  Test Arm: 6 Months After Device Activation (± 31 days) 
Subjects will visit the study site where they will be assessed for pain, 
 
  
 
 Programming adjustments may be made, as 
needed. As per standard practice, 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, healthcare utilization, 
 and medication usage.  
Each subject and the Investigator will evaluate whether or not there has been sufficient 
pain relief to continue stimulation. If the subject and Investigator agree that pain relief has 
been sufficient to continue therapy, the  DTMTM SCS  system will remain active. If the 
subject and Investigator believe that the treatment has not generated sufficient pain relief 
to warrant continued treatment, then the device will be given the option to switch the device 
off and remain in the study. Those subjects will be followed up for an additional 12 months 
using CMM only and continue the study follow-up until the 18 month visit. They will be 
indicated as ‘crossover to CMM’. See Section B.6.1 – Crossover.  
 
B.6.12.  Test Arm: 9 Months After Device Activation (± 31 days) 
Subjects will visit the study site where they will be assessed for pain, 
 
 Programming 
adjustments may be made, as needed. As per standard practice, 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, healthcare utilization and medication usage.  
 
B.6.13. Test Arm: 12 Months After Device Activation (± 45 days) 
Subjects will visit the study site where they will be assessed for pain, 
 
 
 Programming adjustments may be made, as 
needed. As per standard practice, 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, healthcare utilization, 
 and medication usage.  
 
 

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B.6.14.  Test Arm: 18 Months After Device Activation (± 45 days) 
Subjects will visit the study site where they will be assessed for pain, 
 
 Programming 
adjustments may be made, as needed. As per standard practice, 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, healthcare utilization, and medication usage.  
 
B.6.15. Test Arm: 24 Months After Device Activation (± 60 days) 
The follow-up visit 24 Months after Device activaction is the final scheduled study visit. 
Subjects will visit the study site where they will be assessed for pain, 
 
 
 Programming adjustments may be made, as 
needed. As per standard practice, 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, healthcare utilization, 
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 it is determinated that the subject’s 
condition is stable, at which point the Study Completion Clinical Research Form (eCRF) 
should be completed. 
Beyond the 24 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 monitoring of the subject 
will be the responsibility of the subject’s personal physician, as dictated by reasonable 
medical care. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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B.6.16 Control Arm: CMM 
The choice of appropriate Conventional Medical Management will be made by the 
Investigator as determined to be the best standard of care for each individual subject 
i.e. optimized individual conventional therapy. These treatments would be generally 
consistent with the American College of Physicians and the American Pain Society 
Guidelines 
as 
published 
in 
the 
Annals 
of 
Internal 
Medicine 
(http://annals.org/article.aspx?articleid=736814) and European/UK guidelines4,5,6. The 
CMM treatment can be modified at any moment by the investigators based on their clinical 
evaluation and local standard of care. They may also consists of one or more of the 
following treatments: 
• Medications: Over-the-counter Analgesic medications, opioid medications, 
Nonsterioidal anti-inflammatory drugs (NSAIDs), Anticonvulsants, 
Antidepressants, topical analgesics 
• Combined physical and psychological management (CPPM) 
• Physical therapy 
• Back rehabilitation program 
• Spinal manipulation and spinal mobilization 
• Traction 
• Acupuncture 
• Cognitive behavioral therapy (CBT) 
• Biofeedback 
• Nerve blocks 
• Radio frequency ablation 
• Epidural steroid injections 
• Transcutaneous electrical nerve stimulation (TENS) 
• Intradiscal electrothermal therapy (IDET) 
• Nucleoplasty, also called plasma disc decompression (PDD) or similar 
Subjects will continue under CMM therapy until the 24 month visit.  No interventions 
(e.g., facet joint blocks) shall be performed during the 4 weeks leading up to a follow-up 
visit.  
Note: except for the 1 month follow-up visit this is not applicable as the time interval 
between Randomization and 1 month visit may be too short due to organizational 
inconvenience. We recommend however to complete the CMM intervention after the 
Randomization or short after the Randomization and make use of the available time 
windows at the 1 month visit (i.e. 15 days) to make sure this intervention can be 
completed within the proposed time window.     
 
4 Clinical guidelines for the management of low back pain in primary care: an international comparison; Spine. 
26(22):2504-2513, November 15th, 2001. Koes et al 
5 Clinical guidelines for the management of non-specific low back pain in primary care: an updated overview; 
European Spine Journal 27, 2791-2803(2018).Oliveira et al 
6 Low back pain and sciatica in over 16s: assessment and management. NICE guideline. Published 30 November 
2016. www.nice.org.uk/guidance/ng59 

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At the 1 month (±15 days) follow up visit, subjects will be assessed for pain and for 
adverse events, medication usage, healthcare utilization and treatment usage.  
 
At the 3 month (±21 days) follow up, subjects will visit the study site where they will be 
assessed for pain,
 
Subjects will also be assessed for possible adverse events, 
medication usage, healthcare utilization and treatment usage. 
At the 6 month (±31 days) follow up visit, subjects will visit the study site where they 
will be assessed for pain, 
 
 Subjects will also be assessed for possible adverse events, 
medication usage, healthcare utilization, 
 and treatment usage. Subjects will 
have the option to crossover to the test treatment arm if the subject is not receiving 
sufficient pain relief from CMM alone and desires to try the other treatment arm. They will 
be indicated as ‘crossover to DTMTM SCS’.  See Section B.6.1 – Crossover.   
Those subjects that switch to the test arm will be considered a failure in the control arm.  
Subjects that crossover to the test arm will follow the steps described in Sections B.6.5. to 
B.6.13, and the subjects will be followed for another 12 month which includes 1, 3, 6, 9 
and 12 months visits post-device activation.    
 
For those subjects that decide to crossover to the  DTMTM SCS + CMM arm, there will be 
no additional scheduled follow-up visits in the study beyond the 12 month post-device 
activation visit.  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. 
Subjects that continue with CMM and do not cross over, will visit the study site at the 9 
month (±31 days), 12 month (±31 days), and 18 month (±31 days) post-randomization 
for follow up visits, where they will be assessed for pain, 
 
  Subjects will also be 
assessed for possible adverse events, medication usage, healthcare utilization, 
 
 and treatment usage. 
At the 24 months (±60 days) follow up visit (the final scheduled study visit), subjects will 
visit the study site where they will be assessed for pain, 
 
 Subjects will also be 
assessed for possible adverse events, medication usage, healthcare utilization, 
 
and treatment 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.  
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) 

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should be completed. 
 
 
B.6.17.  Unscheduled Visits 
Unscheduled visits may occur at any time during the study for the assessment of possible 
adverse events, changes in pain medication, and therapy adjustments. Each unscheduled 
visit will be documented and recorded on an eCRF. 
 
B.6.18.  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 study site may also call the subject 
periodically to answer subject questions and to check on their health. Participants may also 
be contacted by a representative of SGX to see if they are having problems with the 
equipment and answer questions related to the use of the device. The telephone calls should 
be made two to three weeks before every scheduled visit. 
 
B.6.19.  Other Assessments and Information 
At any time during the study, for those subjects implanted with SCS, 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. 
As per the IntellisTM neurostimulator’s instructions for use: 
- 
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 when allocated to the  DTMTM SCS arm and 
crossover subjects (from CMM to DTMTM SCS): 
• It is recommended that the investigator  instructs all subjects to take the Baseline 
doses of pain medication until the 6 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. The investigator will instruct all subjects to maintain 
stable dosing of medication for at least two weeks prior to scheduled follow-
up visits. 
• For the trial and permanent implants, the clinical site’s standard practice for 
prophylactic pre-surgery antibiotics and post-surgery pain medications will be 

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followed. Investigators will instruct subjects not to change usage of any other 
concomitant pain medications. 
Additional information on Medication Usage when allocated to the CMM arm and 
crossover subjects (from DTMTM SCS to CMM): 
• Subjects should follow the investigator’s instructions. The investigator will instruct 
all subjects to maintain stable dosing of medication for at least two weeks prior to 
scheduled follow-up visits. 
 
B.6.20.  Device Explant 
At any time during the study, a subject with an implanted SCS device system may elect to 
withdraw from the study and have the SCS device system explanted.  Additionally, an 
Investigator may elect to explant the device due to an adverse event. 
The Investigator must follow the appropriate guidelines set forth by the manufacturer (i.e. 
Medtronic) for returning the explanted device and/or lead(s) as well as the accessories 
(charger, patient remote control). 
 
B.6.21.  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. 
 
 
 

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B.6.22.  Study Completion 
All subjects enrolled in the study are expected to complete all scheduled visits through the 
follow up visit 24 months after Device Activation for the test arm or 24 months after they 
are randomized to the control arm. If a control arm (CMM) subject crosses over to the test 
arm (DTMTM SCS), the subject will be followed for 12 months after device activation. If a 
test arm (DTMTM SCS) subject crosses over to the control arm (CMM), the subject will be 
followed until the 18 month follow-up visit. A Study Completion eCRF should be 
completed at the end of this visit. If 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 (i.e. AE is stable). 
 
B.6.23.  Study Suspension and Termination 
Test subjects will be considered to have completed all study requirements following the 
completion of the follow up visit 24 Months after Device Activation and control subjects 
will be considered to have completed all study requirements following the completion of 
the 24 month follow up visit after randomization.  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 EC. 
The Sponsor, the Investigators, or the EC(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 
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.  
In the event of suspension or termination of the study, subjects may be explanted according 
to Device Explant procedures. Subjects may choose to retain the implant and receive 
ongoing stimulation. Subsequent follow-up of the subjects after study completion will be 
the responsibility of the subject’s personal physician.   
The Sponsor 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.  The 
Sponsor will notify Investigators and ECs in writing in the event of study termination.   
The Sponsor 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 24 hours of knowledge of the event 
and to reviewing EC in accordance with its policies 
• Repeated failure to comply with clearance of queries generated during monitoring 
of the study 

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• Inactivity 
 
B.7.  Study Endpoints 
 
B.7.1.  Definition of Analysis Populations  
• Modified Intent to Treat (mITT): All randomized subjects to the test arms who 
successfully complete the Trial Phase and all successfully randomized subjects to 
the control arm. 
• Intent-to-Treat (ITT): All successfully randomized subjects who met all the 
enrollment criteria. 
• Per-Protocol (PP): All test subjects who received a permanent device implant and 
all control subjects who contributed their data to the primary and secondary 
endpoint 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 mITT population. Supportive analyses will be performed for the Intent-to-Treat 
and Per-Protocol population.  
For secondary endpoint analyses incorporating crossover data (i.e. data gathered in 
the post 6-month periods), sensitivity analyses will be performed to examine the 
impact of crossover.  
 
B.7.2.  Effectiveness Assessment Definitions 
• Primary Effectiveness Assessment:  For test subjects who have a successful Trial 
Phase and receive a permanent implant, the Primary Efficacy Assessment occurs at 
the follow up visit 6 months after Device Activation.  For subjects who do not have 
a successful Trial Phase (based on subject’s pain score) or subjects who do not want 
a permanent device implant due to insufficient pain relief (based on subject’s 
discontinuation reason), the Primary Efficacy Assessment occurs at the end of the 
Trial Phase. For control arm subjects, the Primary Efficacy Assessment occurs at 
the 6 months follow up visit post-randomization. 
 
B.7.3.  Primary Endpoint 
Pain rating on the 10 cm Visual Analog Scale (VAS) 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 6 months Post-Permanent Device Activation (Test group) or 6 
months post-randomization (Control group) as compared with 
Baseline.  

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Overall Study Success: The percentage of Individual Responders in the test 
group is shown to be statistically superior to the percentage of Individual 
Responders 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 over time. In addition, data will be 
summarized at the individual time points at 1 month, 3 months, 6 months, 9 months, 
12 months, 18 months, and 24 months.   
• Comparison of change from Baseline in VAS back pain score between test and 
control in statistical tests of non-inferiority and superiority at 1 month, 3 months, 6 
months, 9 months, 12 months, 18 months, and 24 months .  This is calculated as: 
Change from Baseline in Back Pain VAS = Follow-up 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.  
Analysis of results through 6 months will be based on the mITT population. Sensitivity 
analysis of both secondary endpoints will also be performed to assess the impact of 
crossover.  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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B.7.6.  Safety 
Safety will be assessed by characterizing clinically meaningful change in adverse events at 
all study visits. 
Definitions 
An Adverse Event (AE) is any untoward medical occurrence defined as an unintended 
disease or injury or untoward clinical signs (including abnormal laboratory findings 
deemed clinically significant as determined by the investigator) in a subject whether or not 
related to the investigational or commercial medical device. This definition includes events 
related to the study medical devices and events related to the study procedures. An AE is 
also any event related to any underlying medical condition, present at Baseline, which 
increases in severity 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 
severity, treatment/intervention provided, relationship to the device/procedure, and 
resolution. 
As the primary efficacy measure in this study is pain, back or leg pain 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 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 

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attributed to natural history. 
A Serious Adverse Event (SAE) is an adverse event that  
• 
Led to death 
• 
Led to serious deterioration in the health of the subject, that either resulted 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, 
• 
Led 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 
Risk Analysis Section C. 
A Serious Adverse Device Effect (SADE) is an adverse device effect that has resulted in 
any of the consequences characteristic of a serious adverse event. 
An Unanticipated Serious Adverse Device Effect (USADE) is a serious adverse device 
effect which by its nature, incidence, severity or outcome has not been identified in the 
current version of the risk analysis report. Additionally, an Anticipated Serious Adverse 
Device Effect (ASADE) is an effect which by its nature, incidence, severity or outcome 
has been identified in the risk analysis report. 
Those known adverse events related to the device, procedure or therapy are listed in the 
Risk Analysis Section C. 
An anticipated serious adverse device effect (ASADE) is a serious adverse device effect 
which by its nature, incidence, severity or outcome has been previously identified in the 
risk analysis report. Untoward medical occurrences that are not unanticipated, i.e. are 
unsurprising, are identified in the Physician Manual or Protocol and ICF. 
Those known adverse events related to the device, procedure or therapy are listed in Section 
C. 
Device deficiencies will be handled under the post-market surveillance/vigilance system 
from the manufacturer (i.e. Medtronic) as the Intellis system is a CE marked device which 
meets vigilance reporting criteria. 
 
 
 
 
 
 
 

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Reporting 
All device or procedure-related adverse events will be captured from enrollment through 
the completion of the study on the Adverse Event Case Report Form (CRF). However, in 
accordance with ISO 14155 latest version when using commercial medical devices, device 
deficiencies, SAEs, SADEs and USADEs must be reported per the post-market 
surveillance/vigilance system of the manufacturer as specified in the manufacturer's 
labeling/manuals. 
All AEs, Device Deficiencies, SAEs, SADEs and USADEs (see list in section C) reported 
during the study will document severity, treatment/intervention provided, relationship to 
the device/procedure, and resolution. Any USADEs and/or deaths occurring during the 
study procedures will also be evaluated to determine whether the SCS system might have 
malfunctioned, or caused or contributed to the event. 
All SAEs/SADEs/USADEs will be documented and reported to SGX as soon as possible, 
but no later than 24 hours after becoming aware of the SAE. 
 
The SGX contact information for these events is or reporting through eCRF: 
 
 
 
The Investigator or site staff may report an event to the sponsor by email, telephone or fax 
initially, but must follow-up by completing an Adverse Event CRF. The monitored CRF 
should be sent to SGX and, if possible, be accompanied by copies of source documentation 
regarding the event (e.g., physician / nurse notes or summaries / hospitalizations records). 
The Investigator must also report the SAE to the EC according to their local regulations. 
An attempt must be made by the Investigator/site staff to schedule a subject visit as soon 
as feasible following the report of the SAE. In the event of a subject death, all available 
information (e.g. autopsy or other post-mortem findings) should be provided on the CRF. 
An Investigator shall submit a report to the sponsor of any USADE occurring during the 
study as soon as possible, but in no event later than 10 working days after the Investigator 
first learns of the effect. SGX will conduct an evaluation of the event to determine whether 
the event is an anticipated event based on labeling and risk analysis. The Investigator must 
also report the event to the EC if it is determined to be unanticipated. 
All AEs will be followed until the event is resolved (with or without sequelae). If a device-
related event is ongoing at the time of study completion or termination, the subject will be 
followed until resolution or the Investigator determines that the subject’s condition is 
stable. 
 
 
 
 
 
 
 
E-mail: sae@sgx-international.com 

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B.8.  Evaluation Criteria 
Study personnel will be appropriately trained for administration of each test.  
 
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  The 10 cm visual analog scale (VAS) is a well validated and 
widely used scaled psychometric instrument to report pain severity. Subjects will 
score the severity of pain on a 10 cm line, with 0 indicating no pain and 10 
indicating the worst pain imaginable. Subjects will complete a chronic back pain 
VAS in the clinic during scheduled study visits. Subjects will serve as their own 
control for the pain relief endpoint. Each subject’s baseline pain score will be 
compared to the score at follow-up visits. Mean changes from baseline will be 
calculated for the entire cohort. The percentage of subjects who achieved ≥ 50% 
(back) pain relief will also be calculated based on VAS changes from baseline. VAS 
scores collected during the study visits will be used for the primary endpoint. 
 
• 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 

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• 
 
 
 
• 
 
 
 
 
 
 
• 
 
 
 
B.8.2. Safety Measurements 
Adverse Events: Subjects will be assessed for adverse events starting at enrollment and 
continuing through to study completion. If an adverse event occurs, an adverse event CRF 
will be completed. The event will be followed until resolution or determination that the 
subject’s condition is stable.  
The Investigators shall categorize all adverse events for seriousness, severity, and 
relationship. All determinations of severity, device relation, and resolution are made by the 
Investigator and not by the Sponsor.  
For purposes of consistent adverse event reporting and analysis, adverse events will 
categorized using the Medical Dictionary for Regulatory Activities (MedDRA®) 
terminology, consistent with the MedDRA® Term Selection: Points to Consider document. 
Events are grouped by System Organ Classification (SOC) and Preferred Term (PT), 
according to diagnosis and/or event description as provided by the Investigator on the case 
report form.  
 
B.8.3. Health Economic Measures 
Costs and health outcomes (in terms of life-years and quality-adjusted life-years [QALYs]) 
associated will be captured from healthcare utilization data
 
 
 
 
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 superiority test for the primary effectiveness endpoint 
is statistically significant.  

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There are no additional pre-specified subject or study-level success criteria for secondary 
and tertiary endpoints.  
B.9.  Data Collection and Analysis 
 
B.9.1.  Data Collection 
Study data will be collected using a secure Electronic Data Capture (EDC) system. Each 
data field completed via the EDC system is expected to have a verifiable source document.  
The clinical site will enter the data from the source document directly into the EDC system. 
Subject confidentiality will be maintained, and each subject will be identified only by the 
assigned study subject number. Subject names will not be collected. 
Data collection is summarized in Table 1a (DTMTM SCS test arm) & 1b (CMM control 
arm). 
The study data collection from the subjects (which are European citizens) will be processed 
in accordance with the provisions of Regulation 2016/679 of the European Parliament and 
the Council of April 27, 2016 on the protection of natural persons in regarding the 
processing of personal data. 
 
 
Exceptional procedure - in case of exceptional circumstances (e.g. Covid-19 pandemic) 
Remote data collection from the subjects is allowed. This should be evaluated on a case by 
case basis, pending Investigator’s approval based on safety and clinical condition, follow-
up visits may be temporarily completed by alternative means. 
• Visit windows remain in place as described by the Clinical Investigation Plan (CIP) 
and should be maintained as much as possible. Subjects should be contacted via 
phone to confirm AEs, medications and concurrent procedures. All questionnaires 
required at a visit should be obtained via phone, email or via mail based on site 
and/or subject preference. 
• If by phone: site staff will read each question to the subject and record their 
answers. The site staff should initial and date the bottom of each form and indicate 
that this was completed via phone. 
• If by email: the site staff should send the provided pdf questionnaires and 
certification statement to the subjects to complete and return. Subjects can either 
print and manually complete or complete the forms electronically. 
o If manually completed (printed): the subject will be instructed to initial and 
date each page and scan and email or mail the responses back to the sites. 
o If the forms are completed electronically: the subject will be instructed to 
complete the questionnaires and certification statement and return the 
responses to the site. Ideally, questionnaires will be completed and returned 
to the site within 3 business days. 
• If the questionnaires are sent in hard copy by mail: the subjects should be instructed 
to complete the questionnaires and initial and date each page after completion and 
return to site as soon as possible. Ideally, within 3 business days of receipt. 
 
Source documentation should clearly describe the process utilized for each subject at 
each visit when these alternative methods are utilized. 

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Enrolment/Entry criteria visits, procedural visits (trial and IPG) and any unscheduled 
visits required for adverse events obviously should continue to be performed in office 
when possible. If feasible, remote programming ( DTMTM SCS arm) and/or remote 
treatment consultation (CMM arm) can be performed. 
The preferred method of data collection for this study is an in-office visit, however; 
until such a time as deemed safe to return to normal operations, we do not want to place 
the patients and study partners at undue risk. 
 
 

 
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                                          CONFIDENTIAL 
Table 1a - Schedule of Study Activities for the Test arm (DTMTM SCS) 
Assessment 
Pre-Trial 
Trial Phase 
Permanent Implant Phase 
Visit 
Enrollment
/Entry 
Criteria 
Baseline  
Trial 
Implant 
End of 
Trial 
(EoT) 
Permanent 
Implant 
 
Device 
Activation 
(DA) 
Phone Call 
1 Month 
Visit 
Phone Call 
3 Month 
Visit 
Phone Call 
6 Month  
Visit 
Phone Call 
9 Month  
Visit 
Phone Call 
12 Month 
Visit 
Phone Call 
18 Month 
Visit 
Phone Call 
24 Month 
Visit 
Window 
Might be 
combined into 
one visit, if all 
enrollment and 
entry criteria are 
fulfilled at time 
of baseline 
assessment 
- 
0-30 d 
from Trial 
Implant 
0-90 d 
from 
EoT 
0-14 d 
from 
Perm 
Implant 
 
± 15 d 
from 
DA 
 
± 21 d 
from 
DA 
 
± 31 d 
from 
DA 
 
± 31 d 
from 
DA 
 
± 45 d 
from 
DA 
 
 
 
± 45 d 
from 
DA 
 
± 60 d 
from 
DA 
Informed Consent* 
X 
 
 
 
 
 
2-3 Weeks before 1 Month Visit 
 
2-3 Weeks before 3 Month Visit 
 
2-3 Weeks before 6 Month Visit 
 
2-3 Weeks before 9 Month Visit 
 
2-3 Weeks before 12 Month Visit 
 
2-3 Weeks before 18 Month Visit 
 
2-3 Weeks before 24 Month Visit 
 
Medication Usage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pain Intensity (VAS) 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
[X] 
 
[X] 
 
 
 
 
 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
AP/Lateral X-Rays 
 
 
X 
X 
X 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Healthcare Utilization 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Programming§  
 
 
X 
 
 
X 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
Cross over 
 
 
 
 
 
 
 
 
[X] 
 
 
 
 
Study Completion 
 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
X 
[X] Optional activity. 
*For subjects consented prior to the EC approval of the revised consent, they may be reconsented at any study visit. 
§As per the IntellisTM neurostimulator instructions for use. This may also include paresthesia testing. 
Unscheduled visit: VAS, Adverse Event monitoring and medication to be collected 
 
 
 
 
 
 
 

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Table 1b - Schedule of Study Activities for the Control arm (CMM) 
Assessment 
Evaluation phase 
CMM Phase 
Visit 
Enrollment
/Entry 
Criteria 
Baseline  
Phone Call 
1 Month 
Visit 
Phone Call 
3 Month 
Visit 
Phone Call 
6 Month  
Visit 
Phone Call 
9 Month  
Visit 
Phone Call 
12 Month 
Visit 
Phone Call 
18 Month 
Visit 
Phone Call 
24 Month 
Visit 
Window 
Might be combined 
into one visit, if all 
enrollment and 
entry criteria are 
fulfilled at time of 
baseline assessment 
± 15 d 
from 
Baseline 
± 21 d 
from 
Baseline 
± 31 d 
from 
Baseline 
± 31 d 
from 
Baseline 
± 45 d 
from 
Baseline 
 
± 45 d 
from 
Baseline 
± 60 d 
from 
Baseline 
Informed Consent* 
X 
 
2-3 Weeks before 1 Month Visit 
 
2-3 Weeks before 3 Month Visit 
 
2-3 Weeks before 6 Month Visit 
 
2-3 Weeks before 9 Month Visit 
 
2-3 Weeks before 12 Month Visit 
 
2-3 Weeks before 18 Month Visit 
 
2-3 Weeks before 24 Month Visit 
 
Medication Usage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pain Intensity (VAS) 
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 
[X] 
 
 
 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Healthcare Utilization 
 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cross over 
 
 
 
 
[X] 
 
 
 
 
Study Completion 
 
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
X 
[X] Optional activity. 
*For subjects consented prior to the EC approval of the revised consent, they may be reconsented at any study visit. 
Unscheduled visit: VAS, Adverse Event monitoring and medication to be collected 
 
 

 
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                                          CONFIDENTIAL 
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 Pearson Chi-square binomial 
test for superiority at the two-sided 0.05 alpha level. 
H0: The percentage of subjects (P) who achieve a 50% improvement in their back 
VAS pain score at 6 months in the Test group is the same as in the Control 
group. 
PTest  =  PControl  
H1: The percentage of subjects (P) who achieve a 50% improvement in their back 
VAS pain score at 6 months in the Test group is superior to that in the Control 
group. 
PTest  ≠  PControl  
 
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 superior 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 1, 3, 9, 12, 18 or 24 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 two-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 1, 3, 9, 12, 18, or 24 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  
• Change in mean VAS will be evaluated with two-sample t-test of non-
inferiority in means with a 0.65 cm non-inferiority margin at 6 months. 

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H0: The change (C) in subject’s VAS pain intensity score relative to baseline at 
the Primary Efficacy Assessment in the Test group is worse than that of 
subjects in the Control group by more than 0.65 cm. 
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 no more than 0.65 cm 
worse than the mean change from baseline in the control group. 
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 SCS16. 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 cm.  If the null hypothesis is successfully rejected for the 
non-inferiority test, a test for superiority of treatment to control will be performed 
based on a two-sided 0.05 alpha level.  
The following secondary endpoints do not have an associated hypothesis, and no 
significance level will be assigned to statistical tests that may be performed.  
Analysis of results through 6 months will be based on the mITT population. For 
time points after 6 months where crossover is allowed, crossover subjects will be 
counted as failures (i.e. non-responders) for endpoints defined in terms of 
responders, carrying forward the baseline (pre-treatment). Sensitivity analysis of 
both secondary endpoints will also be performed to where crossover subjects are 
censored at the point of crossover. 
 
• 
Comparison of Back Pain Treatment Success (responder rate), measured as 
subjects with at least a 50% reduction in Back Pain VAS, between test and 
control 
• 
Comparison of mean change from Baseline in Back Pain VAS, between test 
and control 
o Repeated measures models will be used to produce estimates for these two 
secondary endpoints, with graphical presentation of the responder rates and 
mean changes from baseline. 
 
 
 
 
 
 
 

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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 in the  DTMTM SCS arm 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. In 
case of missing data Mixed Model for Repeated Measures (MMRM) will be used 
to produce estimates. 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 these analyses will be provided in a separate statistical analysis plan.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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C.  Risk Analysis 
C.1.  Description and Analysis of All Increased Risks to Subjects 
Spinal Cord Stimulation (SCS) Risks: 
 The DTMTM SCS programming approach will be used with commercially available, US FDA 
approved, CE marked 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 
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) 

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• 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 
 
System Revision Risk 
The IntellisTM 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 other 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 

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• 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 
Neurostimulation therapies, such as SCS, are used as an aid in the management of chronic, 
intractable pain that cannot be effectively managed with medications and/or other conservative 
treatments alone. Patients considered for neurostimulation therapy have typically had pain of 
long duration and have failed multiple therapeutic paths.  
Medtronic has carefully designed and tested the IntellisTM Neurostimulation Systems to ensure 
the safety and performance for the treatment of chronic, intractable pain. Medtronic has 
completed an extensive risk analysis to ensure the identification of potential hazards and 
subsequent mitigation of these hazards to eliminate them entirely or reduce them to an 
acceptable level.   
The risks associated with the surgical implantation of the device, device use, and device failures 
are the same as those observed for commercially available SCS devices. With an existing pre-
market application approval for the commercially available IntellisTM  Neurostimulation 
Systems, an established safety profile of probable benefit outweighing risk already exists for 
SCS Therapy for chronic back and/or leg pain. In most cases implantation of SCS is a reversible 
procedure and the system can be turned off or removed. Moreover, stimulation parameters are 
adjustable to minimize or reverse complications and maximize therapeutic effects. System 
output and programming parameters used with the proposed stimulation parameters are within 
the range of the commercially available IntellisTM Neurostimulation Systems. The anticipated 
benefits of the clinical outcomes of SCS therapy per the study design outweigh the overall risk. 
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.  All Investigators and study personnel must provide evidence of training 
in Good Clinical Practice (GCP) in the conduct of clinical trials with human participants.  
 
 
 

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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 as an aid in the management of chronic intractable pain of the trunk and/or 
limbs, stable intractable peripheral vascular disease, or stable intractable angina pectoris. 
The system has been approved by the US FDA, has CE mark certification, and is available 
for commercial use. 
The IntellisTM 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 30 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 US FDA approved, CE mark certified commercially available components will be 
used for the study and used in a maner that is consistent with the approved labeling. 
 
D.1.2.1  Major Components 
Implantable Neurostimulator: IntellisTM 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 
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 

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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 
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.  
 
 
 
 
 
 
 

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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 
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.  
 
 

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D.3.  Labeling 
Instructions for Use:  The study devices will be used in accordance with IntellisTM Manual. 
Labeling: For this study, the IntellisTM System labeling will be consistent with CE marked 
labeling for commercial distribution in Europe. 
 
D.4.  Any Anticipated Changes in the Device 
There are no anticipated changes at this time. 
 
D.5.  Device Accountability 
No device accountability log will be used as this is a commercially available product. 
 
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 
The Sponsor 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 (per latest ISO 141155 version), 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 
study-related 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 the Sponsor’s 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. Paper copies 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 study-related adverse 
events.  Data discrepancies will be addressed by written communication or by telephone with 
the clinical site and/or during clinical site monitoring visits. The Sponsor 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 ISO 14155 latest version, and the recommendations 
guiding physicians in biomedical research involving humans adopted by the 18th World Medical 
Assembly, Helsinki, Finland (1964 and later versions). The Investigator will conduct all aspects 

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of the study in accordance with all national, European Union 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 (or more if 
required) to their EC as per EC guidelines. The Investigator and/or Sponsor, as required by local 
regulations, are required to report in writing to the EC, 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 EC immediately.  
The Investigator is also responsible for recording and assessing the relationship to the study and 
the seriousness of Adverse Events. Investigators must report any severe adverse event (SAE) 
to the sponsor immediately of knowledge of the event and to the EC 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 EC 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 EC. 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 the Declaration of Helsinki 
and ISO 14155 latest version.  
Subjects may be reimbursed for their participation in this study as referenced in the informed 
consent form (ICF) as per the applicable local regulations.  
 
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 the Sponsor or at the request of an 

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Investigator.  A formal change to this study under this investigational plan cannot be initiated 
by Investigator or clinical site personnel without the Sponsor’s approval, EC 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 the Sponsor 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 EC no later than 24 hours following the emergency. 
Deviations from the investigational plan and study requirements (including GCP guidelines) 
will be reviewed by the Sponsor 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 publicly registered in an ICMJE accredited register. Sponsor/Investigator 
Records and Reports will be maintained and provided in accordance to ISO 14155 latest 
version.  No additional records or reports will be maintained. 
 
E. 8 Publication Policy 
See site’s clinical trial agreement (CTA) for the agreed publication policies.  
 
 
 

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F. Appendices 
 
F. 1 Appendix I – Clinical Investigation Plan Signature Page 
 
Signature Page  
 
Comparison of DTMTM SCS Therapy Combined with CMM to CMM Alone in the Treatment 
of Intractable Back Pain Subjects without previous history of Lumbar Spine Surgery 
DTM INT-2020PM2 
Principal Investigator Signature 
I have read this clinical investigation plan and agree to participate in the clinical investigation 
sponsored by SGX International. I agree to conduct this investigation according to the 
requirements of the clinical investigation plan and in accordance with the Declaration of Helsinki, 
ISO 14155 latest version, European and/or local regulations and conditions imposed by the 
reviewing Ethics Committee. I agree to supervise all Sub-Investigators at my site as well as the 
use of all of the devices at my institution and to ensure appropriate informed consent is obtained 
from all subjects prior to inclusion in this study.  
Signature 
Date 
Principal Investigator 
Printed name 
Title 
 
Sponsor Signature 
Confidentiality Statement 
All information concerning the study device supplied by SGX International in connection with this 
study, and not previously published, is considered confidential and proprietary information. This 
information includes the clinical investigation plan, subject informed consent and case report 
forms. This confidential information shall remain the sole property of SGX International, shall not 
be disclosed to others without prior written consent from SGX International and shall not be used 
except in the performance of this study. 
The information developed during the conduct of this clinical study is also considered confidential 
and will be used by SGX International in connection with the development of the study device. 
This information may be disclosed as deemed necessary by SGX International. 
The below-named individuals are authorized to sign this clinical investigation plan and its 
amendments. 
Signature 
Date 
Vice President, Clinical 
Printed name 
Title 
 

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F. 2 Appendix II – List of Abbreviations 
 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASADE 
Anticipated Serious Adverse Device Effect 
CA 
Competent Authorities  
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
DD 
Device Deficiency 
DMP 
Data Management Plan 
DTM 
Differential Target Multiplexed 
EC 
Ethics Committee  
EQ-5D-5L 
European Quality of Life-5 Dimensions 
ICF 
Informed Consent Form 
ID 
Identification 
ISO 
International Organization for Standardization  
MMRM 
Mixed Model Repeated Measures 
MP 
Monitoring Plan 
ODI 
Oswestry Disability Index 
PGIC 
Patient Global Impression of Change 
PI 
Principal Investigator 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SCS 
Spinal Cord Stimulation or Spinal Cord Stimulator 
SD 
Standard Deviation 
SF-12 
Short-Form Health Survey 
USADE 
Unanticipated Serious Adverse Device Effect 
VAS 
Visual Analog Scale 
WMA 
World Medical Association 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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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 Weinstein, J.N., et al., Surgical versus nonoperative treatment for lumbar spinal stenosis four-
year results of the Spine Patient Outcomes Research Trial. Spine (Phila Pa 1976), 2010. 35(14): 
p. 1329-38. 
5 Chen, E., K.B. Tong, and M. Laouri, Surgical treatment patterns among Medicare beneficiaries 
newly diagnosed with lumbar spinal stenosis. Spine J, 2010. 10(7): p. 588-94. 
6 Ragab, A. and R.D. Deshazo, Management of back pain in patients with previous back surgery. 
Am J Med, 2008. 121(4): p. 272-8 
7 Yoshihara H, Yoneoka D. National trends in the surgical treatment for lumbar degenerative 
disc disease: United States, 2000-2009. Spine J 2015;15:265-271. 
8 Bae HW, Rajaee SS, Kanin LE. Nation-wide trends in the surgical management  of lumbar 
spinal stenosis. Spine (Phil Pa 1976). 2013;38:916-926. 
9 Lad SP, Babu R, Ugiliweneza B, Patil CG, Boakye M. Surgery for spinal stenosis: Long-term 
reoperation rates, health case cost, and impact of instrumentation. Spine (Phila Pa 1976) 
2014;39:978-987. 
10 Amirdelfan K, Webster L, Poree L, Sukul V, McRoberts P. Treatment options for fail back 
surgery syndrome patients with refractory chronic pain. An evidence based approach. Spine 
(Phila Pa 1976)2017;42:S41-S52. 
11 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.   
12 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. 
13 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. 
14 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. 
 

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15 Taylor RS, Ryan J, O’Donell R, Eldabe S, Kumar K, North RB. The cost-effectiveness of 
spinal cord stimulation in the treatment of fail back surgery syndrome. Clin J Pain 2010;26:463-
469. 
16 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.