A Single-center, Randomized, Pilot Study to Assess Iovera° Lumbar Medial Branch Cryoneurolysis vs Lumbar Radiofrequency Ablation for Facet Mediated Chronic Low Back Pain
Phase: NA
Conditions: Low Back Pain, Facet Joint Pain
Sponsor: Medical Pain Management Services, PLLC



 
CONFIDENTIAL 
2 of 29 
06FEB2023 
 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
Title of Study: A single-center, randomized, pilot study to assess iovera° lumbar medial 
branch cryoneurolysis vs lumbar radiofrequency ablation for facet mediated chronic low back 
pain 
Principal Investigator(s): 
 
Study Center(s): One center in the United States (US) 
Publications (Reference): None 
Objectives:  
Primary objective: The primary objective of this study is to assess the safety and feasibility 
of iovera° lumbar medial branch cryoneurolysis vs. radiofrequency ablation (RFA) for facet 
mediated chronic low back pain (CLBP). 
Secondary objectives: The secondary objectives of this study are to: 
1. Evaluate safety outcomes (i.e., adverse device effects, serious adverse device effects, 
adverse events [AEs]) related to iovera° treatment vs. RFA; 
2. Evaluate clinical outcomes related to iovera° vs. RFA treatment including pain, functional 
disability, and concomitant medication use (including opioids and analgesics); 
3. Evaluate the treatment success and failure rate of iovera° medial branch cryoneurolysis 
vs. RFA; 
4. Evaluate subject satisfaction with pain management; 
5. Identify subgroups of patients who are most and least likely to benefit from iovera° 
medial branch cryoneurolysis for facet mediated CLBP. 
Methodology:  
This is a single-center, randomized, pilot study in adult subjects with facet mediated CLBP. 
Thirty (30) subjects are planned for initial enrollment and will be randomized 1:1 to receive 
ioveraº medial branch cryoneurolysis or radiofrequency ablation. 
 
This study is designed to determine if a full efficacy RCT can be successfully conducted 
using the procedures and protocols described in the current pilot study protocol, or if protocol 
modifications are necessary before moving forward with a full efficacy RCT. Furthermore, 
the study will assess the feasibility of the outcome measurements employed, construct a 
foundation for sample size calculation, and the acceptability/practicality of conducting the 
full efficacy RCT. 
 
Randomization to treatment groups according to the randomization assignment will be 
performed on the day of treatment. The treatment groups are: 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
3 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• Group 1: subjects will receive iovera° cryoneurolysis to the medial branch nerves of 
the lumbar spine 
• Group 2: subjects will receive RFA to the medial branch nerves of the lumbar spine 
 
Screening  
Subjects will be screened within 30 days of the scheduled ioveraº medial branch 
cryoneurolysis or RFA procedure to determine their eligibility. Subjects must provide 
informed consent – as documented in a study informed consent form (ICF) before performing 
any study related procedure that differs from the standard of care (SOC) at the study site. 
 
During the screening visit, subjects will be assessed for past or present neurologic and 
general medical conditions that in the judgment of the Investigator would preclude them from 
study participation. No procedures other than the site’s SOC will be performed before signed 
informed consent is obtained. After the ICF is signed, demographic information, medical and 
surgical history, concomitant medications/concurrent procedures information, and vital signs 
will be collected. Assessment of the intended treatment areas will be conducted. Subjects will 
assess their pain in the low back region using the Numeric Rating Scale (NRS). Subjects 
must be instructed to report any adverse device effects and adverse events (AEs) to the 
Investigator from the time the ICF is signed through Day 360 (±7 days). 
 
When screening test results are received and the subject is deemed eligible for the study, the 
subject will be notified that he or she is enrolled in the study.  
Method of Assigning Subjects to Treatment 
Randomization scheme 
This is a randomized pilot study. The study will enroll 30 total subjects 1:1 to receive ioveraº 
medial branch cryoneurolysis or radiofrequency ablation on the day of treatment.  
 
The randomization code will be computer generated.  
 
Randomization Procedures 
Once a subject is identified as being qualified for the study in accordance with the eligibility 
criteria, the Investigator or designee will obtain a randomization assignment on the day of 
treatment. The subject will be considered randomized into the study once the study treatment 
is assigned. 
 
Replacement of Subjects 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
4 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
Subjects who withdraw from the study before the study treatment procedure may be replaced. 
Once a subject number is assigned, subject numbers will not be reused; subjects enrolled to 
replace those who withdraw will be assigned a unique subject number and randomized to 
treatment according to the procedures outlined above.  
 
Subjects who are randomized but are withdrawn from the study before receiving the study 
treatment procedure may be replaced. Additionally, subjects may be replaced if insufficient 
and/or incomplete data are noted on safety or clinical outcomes. 
Diagnostic Medial Branch Block (MBB) 
As part of the eligibility criteria, subjects must have undergone two successful diagnostic 
medial branch blocks consisting of two positive blocks with local anesthetic only (i.e., no 
steroids) under fluoroscopic guidance that results in at least 50% relief of primary (index) 
pain for the duration of the local anesthetic used. 
iovera° Medial Branch Block 
ioveraº Treatment 
The iovera° system consists of a reusable, portable Handpiece, along with single patient use 
sterile Smart Tips (i.e., cryoprobes) and disposable nitrous oxide (N2O) cartridges. The 
iovera° system produces the desired effect through initiation of a cooling cycle. Each cooling 
cycle is initiated by fully inserting the Smart Tip into the selected procedure site and 
activating the cryogen flow. The Smart Tip needles are made of stainless steel and have a 
closed tip, fully enclosing the cryogen. The “190” Smart Tip will be used in this study. 
Administration Technique 
iovera° is to be administered in the lumbar spine at the target medial branch nerves 
encompassing one level above and below the involved vertebral levels.  
Subjects will receive a fluoroscopic guided iovera° medial branch block. Blocks will be 
performed with the subject in the prone position under asepsis in the following manner: 
• Record start time of procedure 
• The investigator injects 1% Lidocaine at the treatment site to numb the skin and tissue 
around the facet joint 
• The iovera° Smart Tip is positioned appropriately and a fluoroscopic image is taken to 
confirm the Tip’s position 
• The iovera° Smart Tip is inserted through the skin wheal to the target medial branch 
nerve below the junction of the superior articular and transverse process 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
5 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• Using intermittent fluoroscopic screening with oblique views, the Smart Tip is 
advanced until it strikes bone as close as possible to the target nerve 
• The iovera Smart Tip is positioned, and an x-ray image is taken to confirm the Smart 
Tip’s position 
• With the desired Smart Tip position confirmed, the iovera° handpiece is secured to the 
Smart Tip. The start/stop button on the iovera° handpiece is then pressed to start the 
cycle. 
• After the cycle is complete, the Smart Tip can be removed, and the next treatment 
cycle can commence, ensuring an overlap of the ice ball (if necessary) 
• The Smart Tip is removed and bandages are applied as needed 
• Record stop time of procedure and number of nerves treated 
One freeze cycle will be applied to fully treat the nerve above and below the target joint. The 
exact process will be repeated on the opposite side of the same vertebral level, and the total 
time to place the probe should be recorded. For example, if one level is affected, four nerves 
will be treated (i.e., two nerves bilaterally), and if two levels are involved, twelve nerves will 
be treated (i.e., six nerves bilaterally). 
Note: the subject may be offered midazolam 2-4 mg IV for sedation prior to the procedure. 
 
A complete step-by step administration guide will be provided for the study. 
Radiofrequency Ablation 
The RFA system consists of a Cosman, G4 Generator. The needles used are 20-gauge, 10cm 
long with a 10mm active tip manufactured by Cosman. A grounding pad, also manufactured 
by Cosman, is placed on the upper thigh for each procedure and connected to the G4 
Generator.  
 
Radiofrequency Ablation Procedure 
Radiofrequency ablation is to be administered in the lumbar spine at the target medial branch 
nerves encompassing one level above and below the involved vertebral levels.  
Subjects will receive a fluoroscopic guided RFA medial branch block. Blocks will be 
performed with the subject in the prone position under asepsis in the following manner: 
• Record start time of procedure 
• The Right L4, L5, S1 articular pillars are identified with fluoroscopy at each level and 
the target points are located 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
6 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• A skin wheal is formed using a mixture of 5mL of 1% Lidocaine and 5mL of 0.25% 
Bupivacaine over the target site subcutaneously and deeply 
• A 20-gauge, 10cm needle with a 10mm active tip is inserted using a 15-degree 
oblique view and a 15-degree caudad angle onto the waist of each pillar at each level 
under fluoroscopic guidance 
• Anterior-posterior and oblique neuroforamen views confirm positioning to be outside 
of the neuroforamen and in correct position at each level 
• Stimulation is performed and recorded to confirm proper needle placement by the 
Cosman G4 RF Unit at 50 Hz up to 1.5 volts with no stimulation of the sensory or 
motor roots noted at each level 
• Impedance is within appropriate limits at each level 
• A mixture of 3mL of 0.25% Bupivacaine, 2mL of 1% Lidocaine and 1mL of 
40mg/mL Triamcinolone is divided and injected at each level 
• A lesion is then performed at each level at 80 degrees centigrade for 60 seconds (all 
lesions are at 80 degrees for 60 seconds) 
• The investigator should confirm that no blood is aspirated, no cerebrospinal fluid is 
aspirated, and there are no paresthesias 
• The needles are removed, and bandages applied to the puncture sites 
• The same procedure is carried out on the opposite side 
• Record stop time of procedure and number of nerves treated 
• Radiographs are saved 
 
Note: the subject may be offered midazolam 2-4 mg IV for sedation prior to the procedure.  
 
A complete step-by step administration guide will be provided for the study. 
Study Schema: 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
7 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
 
 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
8 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
Clinical Assessments  
Study assessments are presented in Table 1, Table 2, and below in the sections describing, 
Health Outcomes Assessments, and Safety Assessments.  
Post iovera° or RFA treatment, subjects will report their pain scores (using the NRS pain 
scales to assess pain in the low back region) through Day 360 (±7 days). 
 
At the Day 30 follow up visit, the subject may undergo additional clinical assessments, at 
which point, it may be determined that the subject will need to under other interventional 
procedures (including injections). For the purposes of this study, the subject may only 
undergo major joint and bursa injections, and injections to other regions of the spine not part 
of the lumbosacral spine (i.e., the subject will not be allowed to have injections in the lumbar 
spine and sacrum). 
Number of Subjects (Planned):  
A total of 30 subjects are planned for this pilot study. 
Eligibility Criteria: 
Inclusion Criteria: 
Subjects must meet all of the following inclusion criteria to be eligible for participation: 
1. Male or female volunteers, at least 18 years of age at screening 
2. Primary complaint of axial low-back pain suggestive of unilateral or bilateral facet joint 
involvement (i.e., facet mediated CLBP) 
3. Low back pain is chronic (i.e., > 3 months' duration) 
4. Low back pain score of ≥ 4 (i.e., moderate pain) on the 0 to 10 NRS or functional 
impairment at screening 
5. Successful trial of two diagnostic medial branch blocks consisting of two positive blocks 
with local anesthetic only (i.e., no steroids) that results in at least 50% relief of primary 
(index) pain for the duration of the local anesthetic used or history of a positive response to 
prior radiofrequency treatment (i.e., ≥ 6 months prior to enrollment) 
6. Failure of at least three months of conservative non-operative therapy (e.g., physical 
therapy, chiropractic care, spinal injections, NSAIDs or other appropriate analgesics), 
7. Able to provide informed consent, adhere to the study visit schedule, and complete all study 
assessments 
Exclusion Criteria: 
Subjects who meet any of the following exclusion criteria will not be eligible for 
participation in this study: 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
9 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
1. Active workers’ compensation, personal injury, Social Security disability insurance 
(SSDI), or other litigation/compensation related to the spine 
2. Serious spinal disorders (verified on magnetic resonance imaging (MRI)) that may impact 
outcomes, including any of the following: 
a. Suspected cauda equina syndrome (e.g., bowel/bladder dysfunction) 
b. Infection 
c. Tumor 
d. Traumatic fracture 
e. Systemic inflammatory spondyloarthropathy 
f. Lumbar radiculopathy/radiculitis (i.e., root irritation and deficit) 
g. Neurogenic claudication 
3. Prior lumbar spinal fusion surgery 
4. Comorbidity that, in the judgment of the Investigator, may affect the subject’s ability to 
participate in the study including lumbar radiculopathy and neuropathic pain disorder 
5. Currently pregnant, nursing, or planning to become pregnant during the study 
6. Known contraindication to study devices, including any of the following: 
a. Cryoglobulinemia 
b. Paroxysmal cold hemoglobinuria 
c. Cold urticaria 
d. Raynaud’s disease 
e. Open and/or infected wounds at or near the treatment site 
f. Coagulopathy 
7. 3.5-inch needle cannot be used in the low back region because of habitus 
8. Severe chronic pain disorder that in the opinion of the investigator may impact 
postsurgical outcomes  
9. Presence of any of the following: 
a. Spinal neurostimulator 
b. Intrathecal analgesic drug pump 
10. Current manifestation of poorly controlled mental illness that in the opinion of the 
investigator may meaningfully impact treatment outcomes, including any of the 
following: 
a. Mood disorder (e.g., major depression, bipolar) 
b. Psychotic disorder (e.g., schizophrenia) 
11. Subject received other spine intervention/therapies in the 30 days prior to block 
administration (e.g., spinal injections, minimally invasive therapies, surgical therapies) 
12. Subject received radiofrequency ablation in the low back region ≤ 6 months before study 
enrollment 
13. History, suspicion, or clinical manifestation of: 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
10 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
a. Alcohol abuse or dependence 
b. Illicit drug use 
c. Opioid abuse or dependence (≥40 mg MED PO/day in past 30 days) 
Given the COVID-19 pandemic, the subject must be medically fit/cleared for treatment by 
the investigator. If there is a concern about a subject's recent or potential exposure to 
COVID-19, or if the subject is not medically fit/cleared for treatment due to suspected 
COVID-19 illness/symptoms (or other serious illness), the subject must be excluded per 
Exclusion criterion #4. 
Study Device: 
Name: iovera° System  
Duration of Subject Participation in Study: 
Participation will begin at the signing of the study ICF. No more than 30 days should pass 
between signing of the ICF and the ioveraº or RFA treatment procedure. Subjects will be 
followed up for  360 days (± 7 days) after ioveraº or RFA treatment. Therefore, subjects may 
participate in the study for up to 392 days. 
Study Stopping Rules 
The study may be terminated if the Investigator, or officials from regulatory authorities 
identify conditions during the study that indicate so. 
 
The Investigator will review all serious adverse device effects and serious adverse events 
(SAEs) reported from the clinical study on an ongoing basis and in real time (i.e., as the 
events are reported). The Investigator will be responsible for temporarily halting the study if 
the type, frequency, or seriousness/severity of such events suggests a potential threat to the 
safety of the study participants. If such action is taken, a thorough review of all available data 
will be conducted. Based on the results of this review and discussions with the Investigator 
and/or regulatory authorities as warranted, the study may be restarted or permanently 
terminated. 
 
 
 
 
 
 
 
 
 
In addition, any death will be thoroughly reviewed, and appropriate action taken. 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
11 of 29 
06FEB2023 
 
Removal of Subjects from Therapy or Assessment 
Every reasonable effort will be made to maintain subject compliance and participation in the 
study. Reasons for discontinuation of any subject from the study will be recorded. 
 
If any clinically significant event or condition is uncovered during the study period that might 
render the subject medically unstable or compromise the subject’s post-treatment course, the 
subject will be withdrawn from the study and the event or condition will be reported as an 
AE or SAE. 
 
If a subject withdraws from the study and has an ongoing AE, every effort will be made to 
follow up on such events until satisfactory resolution is obtained or further follow-up is 
otherwise no longer warranted. 
 
Withdrawal Secondary to Adverse Events 
If a subject, experiences an AE that renders the subject incapable of continuing with the 
remaining assessments, the subject will be discontinued from further participation in the 
study. A final evaluation, including the early termination assessments will be performed so 
that the subject’s study participation can be terminated in a safe and orderly manner. 
 
Any subject who discontinues because of an AE will be instructed to notify the study 
personnel of any abnormal symptoms and to visit the study site if medical evaluation is 
needed and the urgency of the situation permits. Any subject exhibiting AEs will receive 
appropriate treatment at the discretion of the Investigator until resolution of the AE. 
 
This study involves a single treatment (i.e., iovera° or RFA); therefore, subjects will not be 
terminated from the ongoing study assessments as long as they are willing and able to 
continue with the follow-up schedule according to the protocol. For emergencies and other 
unscheduled visits to a medical facility other than the study site, medical records will be 
obtained by the Investigator and appropriate information captured in the subject’s case report 
form (CRF). After termination from the study, the subject may be followed for safety 
including monitoring of AEs through Day 360. 
 
Voluntary or Study Investigator Withdrawal 
Subjects are free to discontinue from the study at any time, without prejudice to future 
treatment. A subject may be discontinued from the study if the subject refuses study 
treatment or refuses to comply with study procedures. Subjects will be encouraged to 
complete the study safety assessments. Reasons for discontinuation from the study will be 
recorded. 
 
Early Termination Assessments 
In case of early termination, the following assessments shall be performed: 
• Record date, time, and reason of withdrawal 
• Review adverse events; any ongoing AEs/SAEs will need to be followed to resolution 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
12 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• Record responses to pain assessment: 
o Pain intensity scores on the NRS as “How much pain are you experiencing in 
your low back right now?” 
o Pain intensity scores on the NRS as “What was your worst pain in the past 24 
hours in your low back?” 
o Pain intensity scores on the NRS as “What was your average pain in the past 
24 hours in your low back?” 
Clinical Assessments: 
The following measurements will be assessed at the times specified:  
• Pain intensity scores in the low back region using an NRS measured as follows:  
- 
Current pain intensity (i.e., pain “right now” in the low back region) in the low 
back region at Screening, day of iovera° or RFA  treatment (pretreatment), 
once daily (at 6 pm ±4 hours) from prior to iovera° or RFA treatment to Days 
1-6, at Day 7 (± 2 days), Day 15 (± 2 days), Day 30 (± 5 days), Day 60 (± 5 
days), Day 90 (± 5 days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 
5 days), Day 210 (± 7 days), Day 240 (± 7 days), Day 270 (± 7 days), Day 300 
(± 7 days), Day 330 (± 7 days), Day 360 (± 7 days). 
- 
Daily pain intensity (i.e., average / worst pain over the past 24 hours in the 
low back region) at Screening, once daily (at 6 pm ± 4 hours) from Days 1-6 
after ioveraº treatment, at Day 7 (± 2 days), Day 15 (± 2 days), Day 30 (± 5 
days), Day 60 (± 5 days), Day 90 (± 5 days), Day 120 (± 5 days), Day 150 (± 
5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 days), Day 270 
(± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days).  
• Concomitant medication use (including opioids and analgesics) at Screening, from 
Days 1-6 after ioveraº or RFA treatment, at Day 7 (± 2 days), Day 15 (± 2 days), Day 
30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 days), Day 120 (± 5 days), Day 150 (± 
5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 days), Day 270 (± 7 
days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days). 
• Functional disability at Screening, Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 
days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 
days), Day 240 (± 7 days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 
days), Day 360 (± 7 days). 
• Patient global impression of change at Day 30 (± 5 days), Day 60 (± 5 days), Day 90 
(± 5 days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 
days), Day 240 (± 7 days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 
days), Day 360 (± 7 days). 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
13 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• Patient satisfaction with pain management at Day 30 (± 5 days), Day 60 (± 5 days), 
Day 90 (± 5 days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 
210 (± 7 days), Day 240 (± 7 days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 
(± 7 days), Day 360 (± 7 days). 
 
 
 
 
 
 
 
 
 
Feasibility Endpoints: 
The results of this pilot study will show if the study as designed is feasible. One of the 
following outcomes will be adopted at the conclusion of the trial: 
 
 
 
 
 
 
 
 
Health Outcomes Assessments: 
Health outcome assessments will include: 
• Subject satisfaction with pain management 
• Oswestry Disability Index (ODI) 
• Patient Global Impression of Change (PGIC) 
Safety Assessments:  
Adverse device effects, serious adverse device effects, AEs (including neurologic adverse 
events), and SAEs will be recorded from the time the study ICF is signed through Day 360 (± 
7 days). Any concomitant medications used to treat AEs through Day 360 (± 7 days) will also 
be recorded. 
 
Any other adverse events reported during the study follow-up will also be assessed as safety 
outcomes. 
 
The concepts of AEs and SAEs represent regulatory instruments used to evaluate and 
monitor the safety of clinical study subjects. Therefore, these terms only apply in light of 
their regulatory definition. The term serious, in a regulatory sense, does not necessarily mean 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
14 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
severe. The SAE concept is used primarily to identify, during the conduct of the study, those 
SAEs that may require expedited reporting to regulatory authorities. 
 
Definitions 
Adverse Device Effect: Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) associated with the use of a 
device in subjects, whether or not considered related to the device. This also includes adverse 
device effects related to the use of a device resulting from failure, insufficient or inadequate 
instructions for use, improper or inadequate design, deployment, implantation, installation, or 
operation, or any malfunction of the device, as well as any event resulting from user error (or 
use error) or from intentional misuse of the device. 
Medical Device Report (MDR) Reportable Event: A report of a death, serious injury, or 
malfunction which reasonably suggests that the device:  
• May have caused or contributed to a death or serious injury, or  
• Malfunctioned and the malfunction of the device would be likely to cause or 
contribute to a death or serious injury if the malfunction were to recur. It is presumed 
that once a malfunction has occurred, it will recur. 
 
Serious adverse device effect: An adverse device effect which results in any of the 
consequences characteristic of a serious adverse event: 
• Results in death 
• Is immediately life-threatening (i.e., an event in which the subject was at risk of death 
at the time of the event. It does not refer to an event, which hypothetically may have 
caused death, if it were more severe) 
• Results in permanent impairment of a body function or permanent damage to a body 
structure; or 
• Requires in-patient or prolonged hospitalization 
• Necessitates medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure 
• Results in fetal distress, fetal death, or is a congenital anomaly or birth defect 
“Permanent” means irreversible impairment or damage to a body structure or function, 
excluding impairment or damage that is reversible. A life-threatening injury meets the 
definition of serious injury, regardless of whether the threat was temporary. 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
15 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
Malfunction: Failure of a device to meet its performance specifications or otherwise perform 
as intended. Performance specifications include all claims made in the labeling for the 
device. 
 
Unanticipated Adverse Device Effect: Any serious adverse effect on health or safety, any 
life-threatening problem or death caused by, or associated with a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the investigational plan, application (including a supplementary plan or application), or 
approved labeling, or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
Adverse Drug Event Definitions 
Adverse Event (AE): Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE (also referred to as an adverse 
experience) can be any unfavorable and unintended sign (e.g., abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, without any judgment 
about causality. An AE can arise from any use of the drug (e.g., off-label use in combination 
with another drug) and from any route of administration, formulation, or dose, including an 
overdose. 
 
An AE can be any unfavorable and unintended change in a body structure or body function. 
Adverse events include any clinically significant deterioration of a subject’s medical status. 
The AE may involve any organ or system and can be represented by the new onset or 
deterioration of a disease, a syndrome, a symptom, a physical sign, as well as by findings and 
results of instrumental examinations and laboratory tests. Any medically relevant and 
untoward change after the subject signs the ICF, including frequency or pattern changes for a 
fluctuating condition (e.g., migraine) is considered an AE. 
 
Serious Adverse Event (SAE): An untoward medical occurrence with a drug that at any dose: 
• Results in death 
• Is immediately life-threatening (i.e., an event in which the subject was at risk of death 
at the time of the event. It does not refer to an event, which hypothetically may have 
caused death, if it were more severe) 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity (i.e., a substantial 
disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly or birth defect 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
16 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• Is an important medical event where medical and scientific judgment should be 
exercised in deciding whether SAE reporting is appropriate, such as events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in above definition. Examples of such events include 
intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse 
 
Unexpected Adverse Event: An adverse event in which the nature, severity, or frequency of 
the event is not consistent with the safety information described in the Reference Safety 
Information of the Investigator Brochure or approved product labeling. 
 
Collection and Assessment of Adverse Device Events and Adverse Drug Events 
All adverse events (adverse device events, serious adverse device events, device 
malfunctions, AEs, SAEs) will be collected from the signing of the ICF until Day 360 (± 7 
days), regardless of whether or not they are considered related to the study device, surgical 
treatment, and/or drugs used as part of the treatment regimen. For the study device, 
malfunctions will also be collected. 
 
Any medical condition noted before the subject signs the ICF will be recorded as Medical 
History and is considered a pre-existing condition. Planned hospitalization for a pre-existing 
condition or a procedure described in the protocol, without a deterioration of health, is not 
considered a serious adverse device event or SAE. If a pre-existing condition changes (i.e., 
becomes more severe or more frequent) at any time after the ICF is signed, or after study 
treatment, it is considered an adverse device event and/or AE. 
 
Investigators are not obligated to actively seek safety information after conclusion of the 
study participation. However, if the Investigator learns of any serious adverse device event or 
SAE, including a death, after Day 360 (or at any time after the subject has been discharged 
from the study), and he/she considers the event to be reasonably related to the study 
intervention or study participation, the Investigator must promptly notify the appropriate 
regulatory body. 
 
Severity of Adverse Device Effects and Adverse Drug Events 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
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06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
The severity (or intensity) of an adverse device event or AE should be categorized using the 
following guidelines: 
• Mild: An adverse device event or AE that is easily tolerated by the subject, causing 
minimal discomfort and not interfering with everyday activities. 
• Moderate: An adverse device event or AE that is discomforting and interferes with 
normal everyday activities. 
• Severe: An adverse device event or AE that prevents normal everyday activities. 
The term "severe" is often used to describe the intensity (severity) of a specific event (as in 
mild, moderate, or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as 
"serious," which is based on subject/event outcome or action criteria usually associated with 
events that pose a threat to a subject's life or functioning. Seriousness (not severity) serves as 
a guide for defining regulatory reporting obligations. 
 
Relationship of Adverse Device Effects to Study Device and Adverse Events to Drugs 
The Investigator is required to assess the relationship of the adverse device event, 
malfunction, and/or AE to study device and/or medication received for each occurrence after 
careful medical consideration on a case-by-case basis. The determination of the causal 
relationship to the study device and/or drug(s) will be made using the definitions below: 
• Unrelated: A causal relationship can be easily ruled out (e.g., based on the temporal 
sequence, absence of a reasonable pathophysiological mechanism, or direct evidence 
of actual cause). 
• Unlikely: A clinical event with a temporal relationship to study device and/or drug(s) 
administration which makes a causal relationship improbable and in which other 
drugs, chemicals, or underlying disease provide a plausible explanation; 
• Possible: A clinical event with a reasonable time sequence to administration of the 
study device and/or drug(s) but which could also be explained by a concurrent disease 
or other drugs or chemicals; 
• Probable: A clinical event with a reasonable time sequence to administration of the 
study device and/or drug(s) unlikely to be attributed to a concurrent disease or other 
drugs or chemicals and which follows a clinically reasonable response on withdrawal 
(dechallenge); or 
• Definite: For the study device, it is clear that it caused or contributed to the adverse 
device event and there is no indication of other causes. For drug(s), the 
pharmacological properties of the study drug(s) or of the substance class, and the 
course of the AE after dechallenge and, if applicable, after rechallenge, and/or 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
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06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
specific test indicate involvement of the study drug(s) in the occurrence/worsening of 
the AE, and no indication of other causes exists. 
An additional causality assessment is required for malfunction reports. 
 
Likely to Cause or 
Contribute to a 
serious adverse 
device event 
 
For device malfunctions that have not already been associated with a 
serious adverse device event, there is a reasonable possibility that 
death or serious injury may occur if the malfunction were to recur. 
 
 
Outcome of Adverse Events 
The Investigator will assess the outcome of the adverse device event and/or AE after careful 
medical consideration, on a case-by-case basis. General guidelines are provided below: 
 
Recovered/Resolved: 
 
The event resolved and the subject recovered from the AE. 
Recovered/Resolved 
with Sequelae: 
 
The initial event resolved but has a continuing abnormal 
condition as a result of the AE. 
Not Recovered/ 
Not Resolved: 
 
At the time of last assessment, the event was ongoing, with an 
undetermined outcome. Note: ongoing AEs are not to be 
considered resolved as a result of death 
Recovering/Resolving: 
 
At the time of last assessment, the event was decreasing in 
frequency, severity, etc., and a resolution was expected. 
 
Fatal: 
 
The AE directly caused death. 
Unknown: 
 
There was an inability to access the subject or the subject’s 
records to determine the outcome (e.g., subject withdrew 
consent or was lost to follow-up). 
 
Action Taken with Subject due to an Adverse Device Effect or Adverse Drug Event 
The Investigator will provide any actions taken regarding the subject (e.g., treatment, 
diagnostic tests, laboratory tests, or therapy) for each reported adverse device event and AE. 

 
 
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Clinical Study Protocol 
 
 
 
 
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06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
• None. 
• Medication. 
• Non-pharmaceutical therapy (the specific therapy used must be recorded in the CRF). 
• Discontinued from study. 
• Other (the specific action taken must be recorded). 
 
 
 
 
Reporting of Serious Adverse Device Events and SAEs 
All serious adverse device events, malfunctions, and SAEs will be captured in the subject’s 
case report form within 24 hours of the site becoming aware of the event. Serious adverse 
device event/SAE or malfunction forms will be reported in accordance with local regulations.  
 
The serious adverse device event /SAE report will provide as much of the required 
information as is available at the time. The following minimum information is required for 
reporting a serious adverse device event /SAE: subject identifier, reporting source, event, 
causality assessment, and event outcome. 
 
During the time period between treatment and study discharge, subjects will be instructed to 
contact a designated member of the research team if they experience any adverse device 
effects or AEs during this period. The Investigator and qualified designees will enter the 
information in the electronic data capture (EDC) system as instructed. 
 
Follow-up of Serious Adverse Device Events and SAEs 
Investigators will not wait to receive additional information to fully document the event 
before notifying the appropriate body of the serious adverse device event, malfunction, or 
SAE. The initial report should be followed by a full written summary in the EDC detailing 
relevant aspects of the SAE in question. Where applicable, the investigator will report any 
information relevant to the serious adverse device event malfunction, or SAE from treatment 
records, diagnostic reports, or any other source documents. If information from any relevant 
source documents is not available at the time of the serious adverse device event /SAE report, 
the relevant information will need to be added to the EDC as soon as possible. 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
20 of 29 
06FEB2023 
 
Name of Sponsor/Company: 
The Albany & Saratoga Centers 
For Pain Management  
 
 
 
 
Name of Device: 
iovera° System 
The Investigator will follow all serious adverse device events and SAEs until resolved or the 
condition stabilizes, and further follow-up is not warranted. 
 
If the Investigator is made aware of any serious adverse device event or SAEs after Day 180 
that are believed to be causally related to the study device or drug treatment, these should 
also be reported in the EDC. The event will be followed until resolution, or until adequate 
stabilization is met. 
Safety Endpoints: 
Incidence of treatment-emergent AEs (TEAEs), including adverse device effects, serious 
adverse device effects, AEs, and SAEs through Day 360 (± 7 days) will collected. 
 
The total duration of study follow-up will be 12 months after the iovera° or RFA procedure. 
Adverse device effects, serious adverse device effects, adverse events (AEs), and serious 
adverse events (SAEs) will be recorded from the time the study ICF is signed through Day 
360 (± 7 days). Any concomitant medications used to treat AEs through Day 360 (± 7 days) 
will also be recorded. 
Statistical Methods:  
As the aim of this pilot study is not to assess effectiveness or efficacy, formal hypothesis 
testing will not be determined, and sample size will not be calculated based on desired 
statistical power to detect a treatment effect.  
 
A total of 30 subjects are planned for this pilot study, with 15 randomized to each of the 2 
study groups. 
 
Descriptive statistics (number of subjects, mean, SD, median, minimum, and maximum) will 
be provided for continuous data. Tabulations (number and percentage of subjects) by 
category will be provided for categorical data. Safety data will be summarized descriptively 
by treatment groups and overall, and no statistical testing for comparison of treatment groups 
will be performed for safety variables. 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
CONFIDENTIAL 
21 of 29 
06FEB2023 
 
Table 1: Time and Events Schedule of Study Procedures (Day 1 - Day 180) 
 
Abbreviations: AE = adverse event; d = day; h = hours; ICF = informed consent form; min = minutes; NRS = numeric rating scale; PGIC = Patient Global Impression of Change; RFA 
= radiofrequency ablation; SSDI = Social Security disability insurance 
 
1 
Vital signs will be measured after the subject has rested in a seated position for at least 5 minutes.  
2 
Administer pain intensity NRS prior to iovera/RFA. 
 
 
 
 
 
Screen Visit 
ioveraº 
/RFA 
treatment 
24h to 
144h 
post-block 
Call 
Day 7 
Call 
Day 15 
Call 
Day 
30 
Visit 
Day 60 
Call 
Day 90 
Call 
Day 120 
Call 
Day 
150 
Call 
Day 180 
Visit 
Time 
Window 
≤30 days pre-
block 
Day 1 
±4h 
±2d 
±3d 
±5d 
±5d 
±5d 
±5d 
±5d 
±5d 
Obtain signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
Assess/confirm eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
Record demographics and baseline characteristics 
X 
 
 
 
 
 
 
 
 
 
 
Record/update medical and surgical history 
X 
X 
 
 
 
 
 
 
 
 
 
Record/update prior/concurrent medications and therapies 
X 
X 
 
 
 
 
 
 
 
 
 
Measure vital signs1 
X 
X 
 
 
 
 
 
 
 
 
 
Perform physical examination per standard of care 
X 
 
 
 
 
 
 
 
 
 
 
Perform neurological examination per standard of care 
X 
 
 
 
 
 
 
 
 
 
 
Record NRS pain intensity scores (pain “right now”)2 
 
 
 
 
 
 
 
 
 
 
 
Record history of workers’ compensation, personal injury, 
SSDI, or other litigation related to the spine 
X 
 
 
 
 
 
 
 
 
 
 
Record NRS pain intensity scores (worst / average pain over 
24h) 
X 
 
 
 
 
 
 
 
 
 
 
 Administer the Oswestry Disability Index  
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
 Administer the PGIC 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 Administer ioveraº/RFA treatment, record start & stop times 
of procedure 
 
X 
 
 
 
 
 
 
 
 
 
Capture radiographic images 
 
X 
 
 
 
 
 
 
 
 
 
Record concomitant medications (including opioids and 
analgesics) 
 
 
 
 
 
 
 
 
 
 
 
Record subject satisfaction with pain management 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Record AEs and adverse device effects (beginning at the 
time ICF is signed) 
 
 
 
 
 
 
 
 
 
 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
CONFIDENTIAL 
22 of 29 
06FEB2023 
 
Table 2: Time and Events Schedule of Study Procedures (Day 210 - 360) 
Abbreviations: AE = adverse event; d = day; h = hours; NRS = numeric rating scale; PGIC = Patient Global Impression of Change 
 
 
 
 
Day 210 
Call 
Day 240 
Call 
Day 270 
Call 
Day 300 
Call 
Day 330 
Call 
Day 30 
Visit 
Day 360 
Call 
Time 
Window 
±7d 
±7d 
±7d 
±7d 
±7d 
±7d 
±7d 
Record NRS pain intensity scores (pain “right now”) 
X 
X 
X 
X 
X 
X 
X 
Record NRS pain intensity scores (worst / average pain over 24h) 
X 
X 
X 
X 
X 
X 
X 
 Administer the Oswestry Disability Index  
X 
X 
X 
X 
X 
X 
X 
 Administer the PGIC 
X 
X 
X 
X 
X 
X 
X 
Record concomitant medications (including opioids and analgesics) 
X 
X 
X 
X 
X 
X 
X 
Record subject satisfaction with pain management 
X 
X 
X 
X 
X 
X 
X 
Record AEs and adverse device effects (beginning at the time ICF is signed) 
 
 
 
 
 
 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
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06FEB2023 
 
LIST OF ACRONYMS/ABBREVIATIONS 
 
AE 
Adverse event 
CLBP 
Chronic low back pain 
cm 
Centimeter 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
d 
Day 
DO 
Doctor of Osteopathic Medicine 
EDC 
Electronic data capture 
h 
Hours 
Hz 
Hertz 
ICF 
Informed consent form 
IV 
Intravenous 
L 
Lumbar 
MBB 
Medial branch block 
MDR 
Medical device report 
MED 
Morphine equivalent dose 
mL 
Milliliter 
MRI 
Magnetic resonance imaging 
N2O 
Nitrous oxide 
NRS 
Numeric rating scale 
NSAIDs 
Non-steroidal anti-inflammatory drugs 
ODI 
Oswestry Disability Index 
PGIC 
Patient Global Impression of Change 
RCT 
Randomized controlled trial 
RF 
Radiofrequency 
RFA 
Radiofrequency ablation 
S 
Sacral 
SAE 
Serious adverse event 
SD 
Standard deviation 
SOC 
Standard of care 
SSDI 
Social Security disability insurance 
TEAEs 
Treatment-emergent adverse events 
US 
United States 
 
 
 
 
 
 
 

 
 
CRS-107 (iovera° CLBP) 
Clinical Study Protocol 
 
 
 
 
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06FEB2023 
 
Appendix 1: Subject’s Reported Pain (Numeric Rating Scale)  
Subjects will evaluate their pain in the low back region using an 11-point Numeric Rating Scale 
(NRS), where 0=no pain and 10=worst possible pain. 
The timepoints and assessments are as follows: 
 
Current Pain  
(Pain “right now”) 
Daily Pain  
(Worst/Average pain  
over 24 hours) 
At screening 
Day of iovera° or RFA treatment (pretreatment), 
once daily Days 1-6 (at 6 pm ±4 hours) after 
treatment, at Day 7 (± 2 days), Day 15 (± 2 days), 
Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 
days), Day 120 (± 5 days), Day 150 (± 5 days), Day 
180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 
days), Day 270 (± 7 days), Day 300 (± 7 days), Day 
330 (± 7 days), Day 360 (± 7 days) 
At screening 
Once daily Days 1-6 (at 6 pm ±4 hours) after 
treatment, at Day 7 (± 2 days), Day 15 (± 2 
days), Day 30 (± 5 days), Day 60 (± 5 days), 
Day 90 (± 5 days), Day 120 (± 5 days), Day 
150 (± 5 days), Day 180 (± 5 days), Day 210 
(± 7 days), Day 240 (± 7 days), Day 270 (± 7 
days), Day 300 (± 7 days), Day 330 (± 7 
days), Day 360 (± 7 days) 
 
 
 
Current Pain: Subjects will evaluate how much pain they are currently experiencing (i.e., “How 
much pain are you experiencing in your low back right now?”) at Screening, day of iovera° treatment 
(pretreatment), once daily (at 6 pm ±4 hours) from prior to iovera° treatment to Days 1-6, at Day 
7 (± 2 days), Day 15 (± 2 days), Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 days), Day 
120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 days), 
Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days):  
Pain Intensity Scale (Current Pain) 
 
On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, circle the number that best 
describes your answer to the question “How much pain are you experiencing in your low back right 
now?” (Circle one number only.) 
 
0 
     1      2      3      4      5      6      7      8      9      10 
No pain                                                           Worst possible pain 
Daily Pain: Subjects will evaluate their worst and average level of pain over the past 24 hours 
at Screening, once daily (at 6 pm ±4 hours) from prior to iovera° treatment to Day Days 1-6, at 
Day 7 (± 2 days), Day 15 (± 2 days), Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 days), 
Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 
days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days): 

 
 
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Clinical Study Protocol 
 
 
 
 
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06FEB2023 
 
 
Pain Intensity Scale (Daily Pain) 
 
On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, circle the number that best 
describes your answer to the question “What was your worst pain in the past 24 hours in your low 
back?” (Circle one number only.) 
 
0     1      2      3      4      5      6      7      8      9      10 
No pain                                                           Worst possible pain 
 
On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, circle the number that best 
describes your answer to the question “What was your average pain in the last 24 hours in your low 
back?” (Circle one number only.) 
 
0 
     1      2      3      4      5      6      7      8      9      10 
No pain                                                           Worst possible pain 
 
 

 
 
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Appendix 2: Subject Satisfaction Assessments (Likert Scale) 
Subject satisfaction with pain management will be assessed using Likert scales. 
 
Subject Satisfaction with Pain Management 
The subject's satisfaction with pain management will be conducted at Day 30 (± 5 days), Day 60 
(± 5 days), Day 90 (± 5 days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 
210 (± 7 days), Day 240 (± 7 days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), 
Day 360 (± 7 days).  
 
Subject Satisfaction with Pain Management 
Please circle the number below that best describes your overall satisfaction with your pain 
management. (Select one number only)  
1. Extremely dissatisfied 
2. Dissatisfied 
3. Neither satisfied nor dissatisfied 
4. Satisfied  
5. Extremely satisfied  
 
 

 
 
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Appendix 3: Oswestry Disability Index (ODI) 
Subjects will complete the ODI at Screening, Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 
days), Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 
(± 7 days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days): 
 
 
 

 
 
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Appendix 4: Patients’ Global Impression of Change (PGIC) 
Subjects will complete the PGIC at Day 30 (± 5 days), Day 60 (± 5 days), Day 90 (± 5 days), 
Day 120 (± 5 days), Day 150 (± 5 days), Day 180 (± 5 days), Day 210 (± 7 days), Day 240 (± 7 
days), Day 270 (± 7 days), Day 300 (± 7 days), Day 330 (± 7 days), Day 360 (± 7 days).