Study to Demonstrate the Value of Multiple Modalities and Combining Mechanisms Using the Spectra WaveWriter™ Spinal Cord Stimulator System in the Treatment of Chronic Pain
Phase: NA
Conditions: Chronic Pain, Back Pain
Sponsor: Boston Scientific Corporation

This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distrjbute_without w_!jtten permission fro_m B<!§ton Scientific Cop_oration. 
 
Confidential 
COMBO Study Protocol 
Page 1 of66 
 
 
Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
 
COMBO Study 
Combining Mechanisms for Better Outcomes 
 
A4070 
CLINICAL INVESTIGATION PLAN 
 
NCT03689920- 
 
Sponsored By 
Boston Scientific Neuromodulation Corporation 
25155 Rye Canyon Loop 
Valencia, CA 91355 
United States of America 
 
 
 
 
 

 
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Contact Information 

■ 
 
Confid entia l  
 
Current Version: January 31, 2020 
 
Pa ge 3 of 66 
 
 
 
 
 
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Januar y 
31, 2020 

 
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2. Primary Protocol Synopsis 
 
*For subjects enrolled during protocol Versions A-C. All new subjects will be enrolled 
under the protocol in Appendix A. 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
Primary 
Objective 
To evaluate the effectiveness of Spinal Cord Stimulation (SCS) with 
multiple modalities as compared to conventional SCS in patients with 
chronic pain when using the Boston Scientific Spectra WaveWriter SCS 
System. 
Secondary 
Objectives 
To determine the impact of Spectra WaveWriter SCS System on global 
patient outcomes including quality of life, patient preference, etc. 
Indication(s) for 
Use 
The Spectra WaveWriter Spinal Cord Stimulator (SCS) System is 
indicated as an aid in the management of chronic intractable pain of the 
trunk and/or limbs, including unilateral or bilateral pain associated with 
the following: failed back surgery syndrome, Complex Regional Pain 
Syndrome (CRPS) Types I and II, intractable  low  back pain and leg 
pain. 
Commercial 
Device/System 
BSC Spectra WaveWriter™ SCS System 
Study Design 
Prospective, multi-center, parallel-group randomized controlled trial 
with an adaptive design 

 
Confidential 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
Safety 
Parameters 
Rates of occurrence of all device hardware, device stimulation and 
procedure related non-serious adverse events, all serious adverse events, 
and unanticipated adverse events through the end of the study. 
Primary 
Effectiveness 
Endpoint 
Proportion of subjects with 50% or greater reduction from Baseline Visit 
in average overall pain intensity at 3 months post-randomization, with 
no increase in baseline average daily opioid medications used to treat 
pain. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Confidentia l 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 

 
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COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriterTM Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
Follow-up 
Schedule 
Study events occur at the following time points: 
• 
Screening 
• 
Opioid Medication Lock Visit ( Up to 35 days following 
lnfonned Consent) 
• 
Baseline Period (14 days) 
• 
Baseline Visit (0 - 7 days post Baseline Period) 
• 
Implant Procedure s (up to 90 days post Baseline Visit) 
• 
Hea ling  Period (0  - 28 days) 
• 
Randomization  Visit (Day 0) 
• 
Programmin g Lock Visit (70 - 14 days post-random ization Visit) 
• 
3 Month Vis it (90 + 14 days post-randomization Visit) 
• 
6-Month Visit (180 ± 30 days post-randomi zation Visit) 
• 
9-Month Visit (270 ± 30 days post-randomization Visit) 
• 
Year   I   Visit (365 ± 30 days  post-random iz ation Visit) 
• 
Year 2 Visit (730 ± 30 days post-random iz ation Visit) 
 
Inclusion 
IC I. 
Chronic pain of the trunk and/or lim bs for at leas t 6 months with 
Criteria 
back pain greater or equa l to le g pain. 

 
Confidentia l 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
IS 
IC11. Able to i ndependently read and complete all quest io nnaires and 
assessments provided in Eng lish 
 
ICI 3. Subject signed a valid, !RB-approved in fo rmed consent for m 
(ICF) provided in Englis h 
Exclusion 
Criteria 

 
Confidentia l 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalit ies and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
 
EC7. 
 Any pain-rela te d diag nosis or medic al/ psycholog ical condition 
that, in the clinicia n' s best judgme nt,  might co nfound reporting 
of stud y outco mes (e.g. pelv ic pain, ang ina I p a in, chronic 
mig rain e, brain or spinal co rd tumor) 
 
EC15. Significa nt cog niti ve impair ment at Scree ning that, in the 
opini on of the Investigator, would reasonably be expected to 
impair the study candidate' s abilit y to partic ipate in the study 
EC16. Parti cipatin g (o r intends to partic ipate) in another drug or device 
clinical trial that may influence the data that will be co llected for this 
s tudy 
 
EC18. A female who is breastfeedin g 
EC ! 9. A female o f c hildbearing potential pl anning to get pregnant 
dm ing the co urse of the stud y or not us ing adequate 
co ntrace ptio n 

 
Confidentia l 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriterTM Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
Statistical Methods 
Primary 
Statistical 
Hypothesis 
The primary statistica l hypothes is in this study is that the proportion of 
subjects with 50% or greater reduction from Baseline Visit  in average 
daily overall pain in tensity at 3 month s post randomi zation in the 
WaveWriter group is non-in ferio r compared to the Control (i.e. 
Conventional) group 
Ho: 1t1 - 7rc :S -0.20 
H,: rr1 - rrc > -0.20 
Where 1t1 and rr c are the propo1t io n of subjects with 50 % or greater 
reduction from Baselin e in average daily ove rall pain in tensity at 3 
months post rando mizationwith no increase in baseline  average daily 
opioi d pain medica tion s using Spectra WaveWriter all moda lities and 
conventio nal se ttings, respectively. The study's non -in ferio rity margin is 
0.20. 
 
 
 
 
 
 
 
 
 
 
 

 
Confidential 
 
COMBO Study 
A Study to Demonstrate the Value of Multiple Modalities and Combining 
Mechanisms using the Spectra WaveWriter™ Spinal Cord Stimulator 
System in the Treatment of Chronic Pain 
 
 

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3. Table of Contents 
 
1. 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Co nfide ntia l 

 
 
 
 
 
 
 
 
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3.1. Table of Figures 
 
 
 
3.2. Table of Tables 
 
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4. Introduction 
 
4.1. Chronic Intractable Pain 
 
Chronic intractable pain is often defined as pain persisting for at least 6 months which has 
not responded to conservative treatment(s). The pain may be due to current or past nerve 
injury and causes significant disability, reduced work productivity, reduced quality of life, 
and significant cost burden. 
 
The complexity of chronic pain and the diverse population it affects have resulted in varying 
results between the various treatment approaches including medications, physical therapy, 
stimulation etc. Early treatments for chronic pain typically include over the counter and 
prescription medications. Later treatments like physical therapy and interventional pain 
procedures (e.g. intraspinal injections, vertebroplasty, pulsed radiofrequency (RF) are 
attempted, sometimes followed by chronic high dose opioids and back surgery, if indicated. 
If back surgery is unsuccessful in relieving the chronic pain, the patient can be labeled as 
having failed back surgery syndrome (FBSS). Spinal cord stimulation (SCS) is an option in 
well-selected patients with chronic low back and/or leg pain. 
 
4.2. Spinal Cord Stimulation 
 
SCS is effective for chronic intractable pain associated with a variety of conditions, 
including, but not limited to, FBSS ((Carter et al., 2004, Taylor et al., 2004), complex 
regional pain syndrome (Sears et al., 2011), and low back pain and leg pain (Cameron et al., 
2004). Spinal cord stimulation (SCS) is a less invasive treatment option for FBSS but has 
generally been reserved for patients who have failed multiple, and indeed all possible, repeat 
operations. With SCS, an implanted pulse generator (IPG) delivers electrical current to 
electrode(s) implanted in the epidural space. This current stimulates nerves and can be 
programmed to direct stimulation to the nerves innervating the painful location, resulting in a 
reduction of the intensity of that pain (Kumar et al., 2006). Before an SCS system is 
implanted, a patient often undergoes a screening trial with an electrode that is connected to 
an external stimulator that the patient wears outside of the body. The results of the screening 
trial can predict the patient's outcome with an implanted system (Kumar et al., 2006). 
 
In SCS pain relief is realized when the nerves that innervate the painful region(s) are 
electrically stimulated (North et al., 1990). To increase the chance of success, the electrode 
contacts are programmed based on the patient feedback to various combinations of contact 
polarities (anodes and cathodes), pulse rate (or frequency), pulse amplitude (or current), and 
pulse width. 
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Traditionally, Spinal Cord Stimulation (SCS) has relied on the understanding that to achieve 
pain relief, dorsal column stimulation-induced paresthesia has to be generated around the 
area of pain in order to successfully treat pain (North et al. 1991). However, recent studies 
indicate that effective pain relief may be obtained by employing stimulation without 
paresthesia (Van Buyten et al., 2012, De Ridder et al., 2010, Kapural et al 2015). 
 
 
 
5. Commercial  Device Description  (part of Standard of Care) 
 
The Spectra WaveWriter™ Spinal Cord Stimulator (SCS) System is indicated as an aid in the 
management of chronic intractable pain of the trunk and/or limbs, including unilateral or 
bilateral pain associated with the following: failed back surgery syndrome, Complex 
Regional Pain Syndrome (CRPS) Types I and II, intractable low back pain and leg pain. 
The System includes an Implantable Pulse Generator (IPG), External Trial Stimulator {ETS), 
Remote Control (RC), External Charger, and Clinician's Programmer (CP) and a portfolio of 
lead options. The IPG is rechargeable and is recharged transcutaneously by a charging unit. 
The System is capable of providing multiple waveforms. 
 
The Spectra WaveWriter™ SCS System is approved by the Food and Drug Administration 
(FDA) and will be used per approved Directions for Use (DFU) in this study. 
 
 
6. Study Objectives and Endpoints 
 
6.1. Primary Objective 
 
The primary objective of this study is to evaluate the effectiveness of Spinal Cord 
Stimulation (SCS) with multiple modalities as compared to conventional SCS in patients 
with chronic pain when using the Boston Scientific Spectra WaveWriter SCS System. 
 
 
6.2. Secondary Objective 
 
The secondary objective of this study is to determine the impact of Spectra WaveWriter SCS 
System on global patient outcomes including quality of life, patient preference, etc. 
 
 
6.3. Primary Endpoint 
 
The primary endpoint is the proportion of subjects with 50% or greater reduction from the 
Baseline Visit in average overall pain intensity at 3 months post randomization, with no 
increase in baseline average daily opioid medications used to treat pain.