A Placebo-controlled, Double-blind Evaluation of Safety, Tolerability, and Efficacy of XT- 150 for the Treatment of Facet Joint Osteoarthritis Pain
Phase: PHASE2
Conditions: Facet Joint Pain, Back Pain, Inflammation
Sponsor: Xalud Therapeutics, Inc.



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PROTOCOL APPROVAL PAGE
A Placebo-controlled, Double-blind Evaluation of Safety, Tolerability, and Efficacy of XT-
150 for the Treatment of Facet Joint Osteoarthritis Pain
Protocol XT-150-1-0302
Version 3.0: 08 June 2022
Sponsor’s Approval
The protocol has been approved by Xalud Therapeutics, Inc.

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1. 
PROTOCOL SYNOPSIS 
Sponsor: Xalud Therapeutics, Inc. 
Protocol Number: XT-150-1-0302 
Name of Investigational Product: XT-150 
Protocol Title: A Placebo-controlled, Double-blind Evaluation of Safety, Tolerability, and Efficacy 
of XT-150 for the Treatment of Facet Joint Osteoarthritis Pain 
Study center(s): 3 
Phase: Phase 2a 
Objectives  
• 
Primary: To evaluate the safety and tolerability of a repeat bilateral intra-articular dose of 
XT-150 
• 
Secondary: To establish the analgesic efficacy of a repeat bilateral intra-articular dose of XT-
150 as a treatment for pain in participants with facet joint osteoarthritis (FJOA) 
Study Design  
This is a Phase 2a safety and efficacy study of XT-150 in adult participants experiencing back pain 
due to inflammation of the facet joint osteoarthritis (FJOA) and who are eligible for intra-articular 
glucocorticoid injection, or radiofrequency ablation of medial branches of the primary dorsal ramus of 
the exiting nerve root, which innervates the adjacent facet joints. 
Participants will provide informed consent and meet all study eligibility criteria before any study 
procedures are initiated. Baseline assessments for study eligibility will be completed on the same day 
as or within 1 day before administration of study drug.  
Study drug will be administered at Day 0 and Day 90 by bilateral intra-articular (IA) injection into the 
facet capsule, at the affected spinal level (e.g. L3-4, L4-5, or L5-S1) as determined by imaging (e.g., 
MRI, CT, X-Ray, etc.) and physical exam. Location responsible for facetogenic pain of the spine will 
be determined by clinical, radiological and diagnostic (lidocaine) intra-articular injection.  
Approximately 72 participants will be randomized to placebo or one of two dose treatment groups (24 
participants per treatment group). 
1. 150 µg XT-150 (1.0mL total delivered by two 0.5 mL injections) 
2. 450 µg XT-150 (1.0mL total delivered by two 0.5 mL injections) 
3. Placebo (Sterile saline) (1.0ml total delivered by two 0.5 mL injections) 
Following the first treatment with XT-150 or Placebo at Baseline (Day 0), participants will be 
assessed for safety and efficacy in-clinic on Days 7, 14, 30 and 60. At Day 90, all participants will 
receive a repeat injection with XT-150 or Placebo based on treatment arm assignment at the time of 
randomization. Following Day 90, participants will be assessed approximately monthly through Day 
270. 
Participants who have passed their Day 90 visit or who were enrolled prior to the implementation of 
Protocol V3.0 08Jun2022 and do not reconsent to a second dose will complete the study at Day 180. 
During this visit, all End of Study visit activities should be completed. 
The Schedule of Assessments and Procedures is presented in Table 1. Day 0 is defined as the day of 
study drug administration. Subsequent study days are defined by the number of consecutive calendar 
days after drug administration.  
Number of Participants and Treatment Groups  
Approximately 72 participants will be enrolled in one of 2 XT-150 treatment groups or placebo (24 
participants/group). 

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Inclusion Criteria 
Participants are required to meet ALL of the following inclusion criteria: 
1. Male or female, between 18 and 90 years of age, inclusive. 
2. Sufficiently severe facet arthropathy of lumbar facets as determined by imaging (e.g., MRI, 
CT, X-Ray, etc.) to establish an underlying basis of disease, as determined by usual bony and 
ligamentous signs of osteoarthritis (OA). Use of historical images permitted if obtained 
within the last 12 months.  
3. Complaint of nociceptive, mechanical pain of lumbar spine, in particular pain localized to 
paramedian axis as opposed to midline or radicular. Radicular pain as a secondary finding 
may be allowed if it is in addition to mechanical pain and can be clinically distinguished by 
subject 
4. LBP (Low Back Pain) worsened by activity or motion of region 
5. Have had a positive diagnostic facet pain block with lidocaine; admittance if subject gains 
50% relief of pain within 30 minutes of test injection 
6. Be free of local or intra-articular infection, tumor or other causes of localized LBP, for 
example, spondylolysis/pars defect, and adjacent vertebral body compression fracture based 
on imaging evaluation. 
7. Symptomatic disease because of osteoarthritis, established by imaging of facet joint and 
defined as a worst pain of at least 50 at the Screening Visit and the Baseline (Day 0) Visit 
(based on scale of 0 to 100, with 100 representing “pain as bad as you can imagine”) using 
Visual Analog Scale (VAS). 
8. Stable analgesic regimen during the 4 weeks prior to enrollment. Participants who are not 
currently on any analgesics at the time of enrollment because they have discontinued prior 
analgesic therapy due to intolerance or lack of effect may be included. New analgesics or 
changes to the pre-established regimen during the study, with the exception of rescue 
medication use, are not permitted. 
9. Inadequate pain relief with prior therapies lasting ≥3 months. 
10. In the judgment of the Investigator, acceptable general medical condition  
11. Heterosexually active participants, male and female who are not surgically sterile or post-
menopausal, must agree to use effective contraception, including abstinence, for the duration 
of the study and for 3 months after the study is completed  
12. Have suitable facet joint anatomy for intra-articular injection 
13. Willing and able to return for the follow-up (FU) visits  
14. Able to read and understand study instructions, and willing and able to comply with all study 
procedures 
Exclusion Criteria 
Participants must NOT meet any of the following exclusion criteria: 
1. Hypersensitivity, allergy, or significant reaction to lidocaine or any ingredient of the study 
drug, including double-stranded DNA, 
 
2. Facet injection with corticosteroid in the past 6 months 
3. Lumbar medial branch nerve ablation (e.g., by radiofrequency technique) within the past 12 
months 
4. Prior lumbar fusion surgery 

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5. Prior or existing medial branch nerve stimulation device (e.g., Mainstay device) 
6. Scheduled surgical procedure or nerve ablation to joint within the next 6 months; participant 
agrees not to schedule a surgical procedure, nerve ablation, or added facet injection within 6 
months of study treatment 
7. High peri-operative risks which in the judgment of the investigator preclude a safe facet joint 
injection procedure (e.g. extreme obesity putting injection accuracy at risk, etc.) 
8. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to 
>10mg/day prednisone] or other strong immunosuppressant) 
9. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months.  
10. Currently receiving systemic chemotherapy or radiation therapy for malignancy 
11. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times the 
upper limit of normal for any liver function test (e.g., aspartate aminotransferase, alanine 
aminotransferase, lactate dehydrogenase) 
12. Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion 
indicated), Grade 1 white cell counts (lymphocytes <LLN - 800/mm3; <LLN - 0.8 x 109 /L, 
neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 109 /L) 
13. Positive serology with reflex for human immunodeficiency virus, hepatitis B virus, or 
hepatitis C virus within 4 weeks of commencing the study 
14. Significant neuropsychiatric conditions, dementia, major depression, or altered mental state 
that in the opinion of the Investigator will interfere with study participation 
15. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)  
16. Current treatment with anticoagulants, other than low-dose aspirin. Patients, if medically 
feasible, can interrupt anticoagulant therapy by following local medical practice protocol for 
intra-articular injections for patients on anticoagulant, antiplatelet therapy. 
17. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year 
before the screening visit 
18. Use of any investigational drug or device within 1 month before enrollment or current 
participation in a trial that included intervention with a drug or device; or currently 
participating in an investigational drug or device study. 
19. Any condition that, in the opinion of the Principal Investigator, could compromise the safety 
of the participant, the participant’s ability to communicate with the study staff, or the quality 
of the data 
Investigational Product, Dose and Mode of Administration 
XT-150 is a plasmid DNA (
) formulated in buffered, 
 saline solution. 
Participants will be randomly enrolled into 1 of 3 treatment arms to receive either Placebo or XT-150 
(150 µg, 450 µg) on Day 0 and Day 90. Two 0.5 mL intra-articular (facet) injections (for a total dose 
of 1.0 mL) administered bilaterally will deliver placebo or study drug in a 1:1:1 ratio. 
Diagnostic injection with 0.5 mL lidocaine solution at the affected levels, as determined by imaging 
and physical exam, L3-4, L4-5, or L5-S1 (or the three lumbar cephalad to the sacrum in the case of 
patients with a 6th lumbar vertebral body). The injection will be performed with fluoroscopic 
guidance, using the ipsilateral oblique projection. A spinal needle will be placed in an intra-articular 
position, after local anesthesia of the skin and subcutaneous tissues. The patient will be observed for 1 
hour after this injection. 

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Scheduled Event 
Screen 
Baselinea 
and Dosing 
Follow-up 
Dosing 
Follow-Up 
EOS 
Study Day 
-30 to -1 
0 
7 
(±1) 
14 
(±1) 
30 
(±2) 
60 
(±7) 
90 
(±7) 
120 
(±7) 
150 
(±7) 
180l 
(±7) 
210 
(±7) 
240 
(±7) 
270 
(±14) 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Exam of the Back 
(injection site) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Brief Physical Examination 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record SAEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record Concomitant 
Medicationsg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
HIV, Hepatitis B and C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Chemistries 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CBC with Differential and 
Platelet Count 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test (for 
WOCBP)m 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Whole Blood for Plasmid 
DNA Biodispositionh 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Serum for IL-10 and Anti-IL-
10 Antibody Assessments 
 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
Study Drug Administration 
Enroll Participanti 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Administer Study Drugj 
 
X 
 
 
 
 
Xl 
 
 
 
 
 
 

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Key: AE= adverse event; BMI = body mass index; CBC = complete blood count; FJOA = facet joint osteoarthritis; IL-10 = interleukin 10; SAE = serious 
adverse event; SF12 = short form health survey; VAS = visual analog scale of pain intensity; WOCBP = women of childbearing potential 
a Baseline assessments are performed before injection on Day 0 OR up to one day before study drug administration. Vital signs also assessed at 1 hour after 
study drug administration. 
b Informed consent must be obtained before initiating any study procedures.  
c Obtain demographics (age, race, gender) and complete, relevant, medical, and surgical history (including currently active conditions and inactive pain 
conditions diagnosed) at the Screening visit. Update medical and surgical and pain treatment history at the baseline visit. The physical examination includes the 
injection site for infections or reactions. 
d Record prior medications, including prescription and nonprescription medications and herbal supplements. Update prior medications at the baseline visit. 
e For inclusion in the study, the patient must have sufficiently severe facet arthropathy of lumbar facets as determined by imaging (e.g., MRI, CT) to establish an 
underlying basis of disease, as determined by usual bony and ligamentous signs of OA. Use of historical images is permitted if the images were obtained within 
the last 12 months. 
f Participant global assessment will be recorded by answering the question: "Considering all the ways that facet pain, the pain that brought you into this study, 
affects you, how are you doing today?” on a scale of 1 to 5, 1 being very good (asymptomatic and no limitation of normal activities) to 5, very poor (very 
severe, intolerable symptoms and inability to carry out normal activities) 
g Pain therapy and concomitant medications are recorded
 
. 
h Whole blood for PCR analysis of DNA plasmid biodisposition will be drawn at Baseline, before study drug injection then approximately 4 hours after injection, 
then on Days 7, 14, and 30 scheduled clinic visits.  
i Verify that the participant meets all study inclusion and exclusion criteria before enrollment as close to study drug dosing as possible.  
j Participant will receive one intra-articular, 1-mL dose of study drug by intra-articular injection to the facet capsule at time zero. Participant to be monitored for 
4 hours after administration for signs of study drug reaction. 
k Participants must have a VAS score of at least 50 out of 100 at Screening and at Baseline in order to qualify for study inclusion and treatment.  
l Participants who were enrolled in the study prior to implementation of Protocol Version 3.0 08Jun2022 and either are past their Day 90 visit or do not consent to 
the Day 90 dose will complete the study at Day180. At this visit, all EOS procedures should be completed. 
m A serum pregnancy test will be performed for WOCBP at Screening and Day 270/EOS. A urine pregnancy test will be performed for WOCBP at Day 90 prior 
to study drug administration. 

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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ....................................................................................................1 
PROTOCOL APPROVAL PAGE ...................................................................................................2 
1. 
PROTOCOL SYNOPSIS .............................................................................................3 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............11 
3. 
LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS OF 
TERMS .......................................................................................................................17 
4. 
BACKGROUND AND RATIONALE .......................................................................19 
4.1. 
XT-150 ........................................................................................................................19 
4.2. 
Nonclinical Pharmacology and Toxicology ...............................................................19 
4.3. 
Clinical Experience .....................................................................................................20 
4.4. 
Summary of Known Benefits and Potential Risks .....................................................22 
4.4.1. 
Potential Benefits ........................................................................................................22 
4.4.2. 
Known Risks ...............................................................................................................22 
4.4.3. 
Potential Risks ............................................................................................................22 
4.4.3.1. 
Safety of DNA as a Therapeutic Agent ......................................................................22 
4.4.4. 
Safety of Interleukin-10 ..............................................................................................23 
4.4.5. 
Possible Anticipated Adverse Events and Clinical Monitoring .................................23 
4.4.6. 
Risk-Benefit Summary ...............................................................................................24 
4.5. 
Justification for Dosing Regimen ...............................................................................24 
4.6. 
Population to be Studied .............................................................................................25 
4.7. 
Statement of Compliance ............................................................................................25 
5. 
STUDY PURPOSE, OBJECTIVES AND ENDPOINTS ..........................................26 
5.1. 
Study Objectives .........................................................................................................26 
5.1.1. 
Primary Objective .......................................................................................................26 
5.1.2. 
Secondary Objectives .................................................................................................26 
5.2. 
Study Endpoints ..........................................................................................................26 
5.2.1. 
Safety Endpoints .........................................................................................................26 
5.2.2. 
Efficacy Endpoints ......................................................................................................26 
5.2.2.1. 
Primary Efficacy Endpoint .........................................................................................26 

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5.2.2.2. 
Secondary Efficacy Endpoints ....................................................................................26 
5.2.2.3. 
Exploratory Efficacy Endpoints .................................................................................26 
6. 
STUDY DESIGN .......................................................................................................28 
6.1. 
Description of the Study .............................................................................................28 
6.2. 
Follow Up Assessments ..............................................................................................28 
6.3. 
Number of Participants ...............................................................................................29 
6.4. 
Expected Duration of Subject Participation ...............................................................29 
6.5. 
Method of Treatment Assignment and Blinding ........................................................29 
7. 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF 
SUBJECTS .................................................................................................................30 
7.1. 
Participant Inclusion Criteria ......................................................................................30 
7.2. 
Subject Exclusion Criteria ..........................................................................................31 
7.3. 
Requalification for Entry ............................................................................................32 
7.4. 
Participant Withdrawal Criteria ..................................................................................32 
7.4.1. 
Withdrawal from Study Protocol ................................................................................32 
7.4.2. 
Early Discontinuation from Study Drug Administration ............................................32 
7.5. 
Replacement of Participants .......................................................................................33 
7.6. 
Study Termination by Sponsor and Termination Criteria ..........................................33 
8. 
STUDY DRUGS ........................................................................................................34 
8.1. 
Formulation and Preparation of Study Drug ..............................................................34 
8.1.1. 
Directions for Use .......................................................................................................34 
8.1.2. 
Instructions for Storage and Handling ........................................................................34 
8.1.3. 
Placebo Formulation ...................................................................................................34 
8.2. 
Investigational Product Administration ......................................................................35 
8.3. 
XT-150 Blinding .........................................................................................................35 
8.4. 
Compliance .................................................................................................................35 
8.5. 
Previous and Concomitant Medications and Substances ............................................35 
8.5.1. 
Prohibited Medications ...............................................................................................35 
8.5.2. 
Rescue Medication ......................................................................................................36 
 
 
8.6. 
Accountability Procedures ..........................................................................................36 
8.7. 
Study Drug Handling and Disposal ............................................................................36 
9. 
STUDY PROCEDURES ............................................................................................37 

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9.1. 
Screening ....................................................................................................................37 
9.2. 
Baseline (Day-1 or Day 0) ..........................................................................................38 
9.3. 
Day 0 ...........................................................................................................................39 
9.4. 
Day 90 (±7 days) ........................................................................................................40 
9.5. 
Between Clinic Visits .................................................................................................41 
9.6. 
Follow Up Visits – Day 7 (±1 day), Day 14 (±1 day), Day 30 (±2 Days), Day 
60 (±7 days), Day 120 (±7 days), Day 150 (±7 days), Day 180 (±7 days), 
Day 210 (±7 days) and Day 240 (±7 days) .................................................................41 
9.7. 
End of Study Visit – Day 270 (±14 days) ...................................................................42 
10. 
ASSESSMENT OF SAFETY .....................................................................................43 
10.1. 
Safety Parameters .......................................................................................................43 
10.2. 
Adverse Events ...........................................................................................................43 
10.3. 
Adverse Event Reporting ............................................................................................43 
10.4. 
Definitions ..................................................................................................................44 
10.4.1. 
Adverse Event .............................................................................................................44 
10.4.2. 
Suspected Adverse Drug Reaction .............................................................................45 
10.4.3. 
Life-Threatening AE or Life-Threatening Suspected Adverse Drug Reaction ..........45 
10.4.4. 
Serious AE or Serious Suspected Adverse Reaction ..................................................45 
10.4.4.1. 
Serious Adverse Event Definition Clarifications .......................................................45 
10.4.5. 
Unexpected AE or Unexpected Suspected Adverse Drug Reaction ..........................46 
10.5. 
Adverse Event Classification ......................................................................................46 
10.5.1. 
Relationship to Investigational Drug ..........................................................................46 
10.5.2. 
Severity .......................................................................................................................47 
10.6. 
Adverse Event Follow-up ...........................................................................................47 
10.7. 
Adverse Events of Special Interest .............................................................................47 
10.7.1. 
Adverse Events of Noted Interest in IL-10 Protein Trials ..........................................47 
10.7.2. 
Localized Signs of Infection or Inflammation at the Injection Site ............................48 
10.8. 
Toxicity Management .................................................................................................48 
10.9. 
Risks for Women of Childbearing Potential or During Pregnancy ............................48 
11. 
ASSESSMENT OF EFFICACY PARAMETERS .....................................................49 
11.1. 
Efficacy Parameters ....................................................................................................49 
11.1.1. 
VAS ............................................................................................................................49 
11.1.2. 
ODI .............................................................................................................................49 

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11.1.3. 
IPAQ ...........................................................................................................................49 
11.1.4. 
SF-12 ...........................................................................................................................49 
11.1.5. 
Participant Global Assessment ...................................................................................49 
 
 
12. 
ASSESSMENT OF ANTI-IL-10 ANTIBODIES .......................................................50 
13. 
ASSESSMENT OF XT-150 PLASMID DNA BIODISTRIBUTION .......................51 
14. 
STATISTICAL METHODS .......................................................................................52 
14.1. 
Determination of Sample Size ....................................................................................52 
14.2. 
Analysis Populations ..................................................................................................52 
14.3. 
Analysis of Study Population and Participant Characteristics ...................................52 
14.4. 
Safety Analysis ...........................................................................................................52 
14.5. 
Efficacy Analysis ........................................................................................................53 
 
 
 
 
 
 
 
 
14.6. 
Bioanalytical Analyses ...............................................................................................54 
14.7. 
Handling of Dropouts and Missing, Unused, and Spurious Data ...............................54 
14.8. 
Termination Criteria ...................................................................................................54 
14.9. 
Deviation Reporting ....................................................................................................54 
15. 
INVESTIGATOR REQUIREMENTS .......................................................................55 
15.1. 
Protocol Adherence ....................................................................................................55 
15.1.1. 
Investigator or Designee Experience ..........................................................................55 
15.2. 
Case Report Forms .....................................................................................................55 
15.3. 
Source Document Maintenance ..................................................................................55 
15.4. 
Study Monitoring Requirements .................................................................................55 
15.5. 
Study Completion .......................................................................................................56 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................57 
17. 
PROTECTION OF HUMAN PARTICIPANTS ........................................................58 
17.1. 
Informed Consent .......................................................................................................58 
17.2. 
IRB Approval ..............................................................................................................58 
18. 
DATA HANDLING AND RECORD KEEPING ......................................................59 
18.1. 
Direct Access to Source Data/Documentation ...........................................................59 

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18.2. 
Study Drug Accountability .........................................................................................59 
18.3. 
Retention of Records ..................................................................................................59 
19. 
FINANCING AND INSURANCE .............................................................................60 
20. 
PUBLICATION POLICY ..........................................................................................61 
21. 
REFERENCES ...........................................................................................................62 
APPENDIX 1. CLINICAL LABORATORY TESTS ................................................................64 
APPENDIX 2. PROTOCOL SIGNATURE PAGE ....................................................................65 
 

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LIST OF TABLES 
Table 1: 
Schedule of Assessments and Procedures ....................................................................8 
Table 2: 
Abbreviations ..............................................................................................................17 
Table 3: 
Human Clinical Trials in Osteoarthritis with XT-150 ................................................20 
Table 4: 
Final Drug Product Quantitative Composition Per Vial .............................................34 
Table 5: 
Guidelines for Assessing Relationship of Event to Study Drug .................................47 
Table 6: 
Guidelines for Severity Assessments ..........................................................................47 
 

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3. 
LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS 
OF TERMS 
Table 2: 
Abbreviations  
Abbreviation  
Explanation 
AE 
Adverse event 
BMI 
Body mass index 
CBC 
Complete blood count 
COVID-19 
Coronavirus Disease of 2019 
CTCAE 
Common Terminology Criteria for Adverse Events (V5.0) 
CRF 
Case report form 
CRO 
Contract Research Organization 
CT 
Computed Tomography  
DNA 
Deoxyribonucleic acid  
ePRO 
Electronic Patient Reported Outcome 
FDA 
Food and Drug Administration 
FJOA 
Facet Joint Osteoarthritis 
FU 
Follow-up 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HIV 
Human Immunodeficiency Virus 
IA 
Intra-articular 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IL-10 
Interleukin-10 
IPAQ 
International Physical Activity Questionnaire 
IRB 
Institutional Review Board 
IT 
Intrathecal  
ITT 
Intent-to-treat 
LBP 
Lower back pain 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed Model Repeated-Measures 

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4.4. 
Summary of Known Benefits and Potential Risks 
4.4.1. 
Potential Benefits 
Participants will receive active investigational product or phosphate-buffered saline injection 
(placebo). The effects of XT-150 for FJOA have not been previously explored, however 
potential therapeutic benefits of XT-150 for the treatment of FJOA pain are: 
• Increased mobility for many weeks following a single dose of XT-150 
• Reduction in requirement for pain medications and therapies 
• Reduction in pain symptoms for many weeks following a single dose of XT-150. 
4.4.2. 
Known Risks 
Intra-articular injection in the knee with XT-150 has been well tolerated in clinical trials of OA 
pain. Based on multiple animal studies and 4 clinical trials in osteoarthritis, XT-150-related 
adverse events are most commonly minor injection site reactions. 
4.4.3. 
Potential Risks 
Nonclinical studies and clinical studies with XT-150 are described in the IB. XT-150 posed 
minimal risk in these studies. General risks associated with IA injection are injection site 
reactions and infection, which will be explicitly captured in follow-up safety assessments. 
4.4.3.1. 
Safety of DNA as a Therapeutic Agent 
DNA as a therapeutic agent has been well tolerated. The main theoretical safety concerns 
regarding the clinical use of DNA are that they might integrate with the host/patient DNA, or 
that injection of foreign DNA might stimulate anti-DNA antibodies or an autoimmune reaction 
(Prazeres 2014).  
With both DNA vaccines and DNA plasmids, the risk of integration was repeatedly found to be 
low with years of research into the possibility (FDA 2007; Prazeres 2014). With plasmids, the 
potential for integration has been removed by excluding any sequences that might drive 
homologous recombination and integration into the genome. In fact, excluding these elements 
lowers the risk of plasmid integration to less than the rate of naturally occurring mutations 
(Prazeres 2014). XT-150 has been designed to transiently express a variant of human IL-10 
without integrating into the genome. 
Immunogenicity of DNA appears to be low (Ferraro 2011), and correlates to the lack of success 
of DNA agents (even pathogenic bacterial sequences) as vaccines. No link has been found 
between plasmid DNA injections and any clinical markers of autoimmunity (Prazeres 2014). In 
addition, DNA plasmids have been used in research and development for 25 years. Synthetic 
vectors share the non-infectious properties of viral vectors and elicit low immunogenicity and 
lower toxicity compared to viral vectors (Xu 2011; Gôrecki 2006). 

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4.4.4. 
Safety of Interleukin-10 
Published studies in the literature have reported IL-10 protein therapy to be safe in humans. The 
safety of IL-10 protein injections was studied in healthy volunteers at doses up to 100 μg/kg. 
Details of these studies can be found in the IB. 
After injection in healthy volunteers at doses up to 100 μg/kg, wild-type human IL-10 protein 
was found to be rapidly degraded with a half-life of 2.0 to 4.5 hours (Chernoff 1995; Huhn 1996; 
Huhn 1997; Milligan, 2005). In the Huhn, 1997 study, after intravenous administration of high 
doses of IL-10 protein (100 µg/kg), 42% (15/36) of the volunteers experienced flu-like adverse 
effects, the most common of which were headache (11/36 participants, 31%), fever (5/36, 14%), 
and back pain (3/36, 8%). Pharmacodynamic effects from intravenous IL-10 treatment included 
transient increases in neutrophils and monocytes, and decreases in lymphocytes, which peaked 
around 6 hours after injection (Chernoff, 1995). When given intravenously, IL-10 was also found 
to inhibit production of the cytokines IL-1β and tumor necrosis factor-alpha (TNF-α), and reduce 
T-lymphocyte stimulation. 
Recombinant human IL-10 has been clinically tested as a therapy in humans in a number of 
indications without serious or irreversible side effects. In these trials, IL-10 injections of up to 25 
µg/kg were reported to be well tolerated. With chronic intravenous and high doses, statistically 
significant hematological changes were observed, as well as fever. Adverse events of 
neutrophilia, headache, injection site pain, anemia, and nausea were observed with daily dosages 
in patients with Crohn’s Disease. 
As an anti-inflammatory agent, the biological activity of IL-10 is different than that of other 
interleukins. Exogenous IL-10 is the only interleukin shown to be well tolerated. However, the 
anti-inflammatory activity of IL-10 treatment could mask latent infections (Moore, 2001). Since 
IL-10 has been theorized to mask latent infections, any participant who has a current 
autoimmune condition or documented immunodeficiency, has a history of immunosuppression, 
or is currently receiving treatment with immunosuppressive agents is excluded from this study.  
Note that XT-150 is a sterile aqueous formulation of a plasmid designed to transiently express a 
proprietary variant of IL-10. XT-150 expression of the variant IL-10 is expected to be safer than 
systemic injection of active IL-10 protein as therapy for the following reasons:  
• Rather than injections of IL-10 protein, XT-150 treatment will result in IL-10v levels that 
exist transiently and at a much lower concentration.  
• The IL-10v levels from XT-150 expression will be localized in the intra-articular joint 
space. Low systemic levels of IL-10 from XT-150 treatment may be present for short 
periods of time and if present are unlikely to lead to adverse effects, 
 
. 
4.4.5. 
Possible Anticipated Adverse Events and Clinical Monitoring 
Anticipated AEs for which there will be specific safety monitoring in humans will be based on 
the preclinical studies 
 as well as the published reports of studies of 
IL-10 protein injections to healthy volunteers. In a publication of the incidence and 
characteristics of intra-articular facet joint injection by Kim, 2020, the incidence of major 
procedure-related complications, such as local injections site infection, was demonstrated to be 

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4.6. 
Population to be Studied 
About 72 adult participants with a diagnosis of moderate to severe pain due to facet osteoarthritis 
will be enrolled in this study. 
4.7. 
Statement of Compliance 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), the 
ethical principles of the Declaration of Helsinki, and applicable regulatory and Institutional 
Review Board (IRB) requirements. 

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6. 
STUDY DESIGN 
6.1. 
Description of the Study 
This is a Phase 2a, safety and efficacy study of XT-150 in adult participants experiencing back 
pain due to inflammation of the facet joint (Facet Joint Osteoarthritis [FJOA]) and who are 
eligible for intra-articular glucocorticoid injection, or radiofrequency ablation of medial branches 
of the primary dorsal ramus of the exiting nerve root, which innervates the adjacent facet joints. 
Participants will provide informed consent and meet all study eligibility criteria before any study 
procedures are initiated. Baseline assessments for study eligibility will be completed on the same 
day as or within 1 day before administration of study drug.  
Study drug will be administered at Day 0 and Day 90 by intra-articular (IA) injection into the 
facet capsules, bilaterally at the affected spinal level (e.g. L4-5 and L5-S1). Location responsible 
for facetogenic pain of the spine will be determined by clinical, radiological and diagnostic 
(lidocaine) intra-articular injection. 
Up to 72 participants will be randomized to one of two dose treatment groups or to placebo (24 
participants per treatment group).  
1. 150 µg XT-150 (1.0 mL total delivered by two 0.5 mL injections) 
2. 450 µg XT-150 (1.0 mL total delivered by two 0.5 mL injections) 
3. Placebo (Sterile phosphate-buffered saline for injection, PBS) (1.0 mL total delivered by 
two 0.5 mL injections).  
Following the first treatment with XT-150 or Placebo at Baseline (Day 0), participants will be 
assessed for safety and efficacy in-clinic on Days 7, 14, 30 and 60. At Day 90, all participants 
will receive a repeat injection with XT-150 or Placebo based on treatment arm assignment at the 
time of randomization. Following Day 90, participants will be assessed approximately monthly 
through Day 270. 
Participants who have passed their Day 90 visit or who were enrolled prior to the implementation 
of Protocol V3.0 08Jun2022 and do not reconsent to a second dose will complete the study at 
Day 180. During this visit, all End of Study visit activities should be completed. 
The Schedule of Assessments and Procedures is presented in Table 1. Day 0 is defined as the day 
of study drug administration. Subsequent study days are defined by the number of consecutive 
calendar days after drug administration.  
6.2. 
Follow Up Assessments 
All participants will be assessed for physical examination findings and vital signs following 
signing of the informed consent form (ICF) and for AEs and SAEs, throughout the study for each 
treatment group.  
Serum samples will be collected from all participants to test for the presence of anti-IL-10 
antibodies and IL-10 protein. Samples will be analyzed using a validated assay by an 
independent, central bioanalytical laboratory. Procedures for collection, storage, and shipping of 
immunogenicity samples are described in the study Lab Manual.  

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Whole blood samples will be collected from all participants to test for the presence of XT-150 
plasmid. Samples will be analyzed using a validated assay by an independent, central 
bioanalytical laboratory. Procedures for collection, storage, and shipping of immunogenicity 
samples are described in the study Lab Manual. 
Efficacy assessments will be performed at Baseline, on Day 7, Day 14, Day 30, and 
approximately monthly thereafter for up to 9 months. Efficacy endpoints will be evaluated at 
each study visit and overall. 
A telephone call documenting safety and efficacy assessments may be used for participants 
unable to physically attend follow up visits due to COVID-19 infection or SARS-CoV-2 
exposure concerns. Home services may be employed for blood collections. 
6.3. 
Number of Participants 
Up to 72 participants will receive study drug administration and evaluated. 
6.4. 
Expected Duration of Subject Participation  
Subject participation will require a commitment of approximately 9 months of safety, 
tolerability, and efficacy evaluation. In addition, a screening visit will occur up to 30 days before 
enrollment.  
Baseline assessments for study eligibility will be completed within one day before study drug 
administration. Day 0 is defined as the day of study drug administration. Subsequent study days 
are defined by the number of consecutive calendar days thereafter. 
Follow-up visits will occur on Study Day 7, Study Day 14, Study Day 30, and approximately 
monthly thereafter. 
6.5. 
Method of Treatment Assignment and Blinding 
After informed consent has been obtained, participants will be screened for study eligibility 
before enrollment.  
Participants will be randomly enrolled into one of 3 groups, two XT-150 treatment groups (150 
μg or 450 μg) or placebo.  
Instructions for study drug preparation and dosing are given in Section 8. 

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7. 
SELECTION, DISCONTINUATION, AND WITHDRAWAL OF 
SUBJECTS 
To be enrolled in this study, all participants must meet all of the following inclusion criteria and 
none of the exclusion criteria. 
7.1. 
Participant Inclusion Criteria 
Participants are required to meet ALL of the following inclusion criteria: 
1. Male or female, between 18 and 90 years of age, inclusive.  
2. Sufficiently severe facet arthropathy of lumbar facets as determined by imaging (e.g., 
MRI, CT, X-Ray, etc.) to establish an underlying basis of disease, as determined by usual 
bony and ligamentous signs of osteoarthritis (OA). Use of historical images permitted if 
obtained within the last 12 months. 
3. Complaint of nociceptive, mechanical pain of lumbar spine, in particular pain localized to 
paramedian axis as opposed to midline or radicular. Radicular pain as a secondary finding 
may be allowed if it is in addition to mechanical pain and can be clinically distinguished 
by subject 
4. LBP (Low Back Pain) worsened by activity or motion of region 
5. Have had a positive diagnostic facet pain block with lidocaine; admittance if subject 
gains 50% relief of pain within 30 minutes of test injection 
6. Be free of local or intra-articular infection, tumor or other causes of localized LBP, for 
example, spondylolysis/pars defect, and adjacent vertebral body compression fracture 
based on imaging evaluation. 
7. Symptomatic disease because of osteoarthritis, established by imaging of facet joint and 
defined as a worst pain of at least 50 at the Screening Visit and the Baseline (Day 0) Visit 
(based on scale of 0 to 100, with 100 representing “pain as bad as you can imagine”) 
using Visual Analog Scale (VAS). 
8. Stable analgesic regimen during the 4 weeks prior to enrollment. Participants who are not 
currently on any analgesics at the time of enrollment because they have discontinued 
prior analgesic therapy due to intolerance or lack of effect may be included. New 
analgesics or changes to the pre-established regimen during the study, with the exception 
of rescue medication use, are not permitted. 
9. Inadequate pain relief with prior therapies lasting ≥3 months. 
10. In the judgment of the Investigator, acceptable general medical condition  
11. Heterosexually active participants, male and female who are not surgically sterile or post-
menopausal, must agree to use effective contraception, including abstinence, for the 
duration of the study and for 3 months after the study is completed  
12. Have suitable facet joint anatomy for intra-articular injection 
13. Willing and able to return for the follow-up (FU) visits  

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14. Able to read and understand study instructions, and willing and able to comply with all 
study procedures 
7.2. 
Subject Exclusion Criteria 
Participants must NOT meet any of the following exclusion criteria: 
1. Hypersensitivity, allergy, or significant reaction to lidocaine or any ingredient of the 
study drug, including double-stranded DNA, 
 
2. Facet injection with glucocorticoid/corticosteroid in the past 6 months 
3. Lumbar medial branch nerve ablation (e.g., by radiofrequency technique) within the past 
12 months 
4. Prior lumbar fusion surgery 
5. Prior or existing medial branch nerve stimulation device (e.g. Mainstay device) 
6. Scheduled surgical procedure or nerve ablation to joint within the next 6 months; 
participant agrees not to schedule a surgical procedure, nerve ablation, or added facet 
injection within 6 months of study treatment 
7. High peri-operative risks which in the judgment of the investigator preclude a safe facet 
joint injection procedure (e.g. extreme obesity putting injection accuracy at risk, etc.) 
8. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent 
to >10mg/day prednisone] or other strong immunosuppressant) 
9. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 
months.  
10. Currently receiving systemic chemotherapy or radiation therapy for malignancy 
11. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times 
the upper limit of normal for any liver function test (e.g., aspartate aminotransferase, 
alanine aminotransferase, lactate dehydrogenase) 
12. Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion 
indicated), Grade 1 white cell counts (lymphocytes <LLN - 800/mm3; <LLN - 0.8 x 109 
/L, neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 109 /L) 
13. Positive serology with reflex for human immunodeficiency virus, hepatitis B virus, or 
hepatitis C virus within 4 weeks of commencing the study 
14. Significant neuropsychiatric conditions, dementia, major depression, or altered mental 
state that in the opinion of the Investigator will interfere with study participation 
15. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical 
treatments)  
16. Current treatment with anticoagulants, other than low-dose aspirin. Patients, if medically 
feasible, can interrupt anticoagulant therapy by following local medical practice protocol 
for intra-articular injections for patients on anticoagulant, antiplatelet therapy. 

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17. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 
year before the screening visit 
18. Use of any investigational drug or device within 1 month before enrollment or current 
participation in a trial that included intervention with a drug or device; or currently 
participating in an investigational drug or device study. 
19. Any condition that, in the opinion of the Principal Investigator (PI), could compromise 
the safety of the participant, the participant’s ability to communicate with the study staff, 
or the quality of the data 
7.3. 
Requalification for Entry 
Participants not fulfilling the entry criteria and not treated may be rescreened for participation if 
their eligibility characteristics have changed. The screening lidocaine facet injection procedure 
may be repeated one time to identify the joint that is causing pain. 
7.4. 
Participant Withdrawal Criteria 
7.4.1. 
Withdrawal from Study Protocol 
Participants who wish to withdraw completely from this clinical study should be encouraged to 
complete the assessments for Day 270/Termination. However, participants may withdraw 
consent to participate in this study at any time without penalty or loss of benefits to which the 
participant is otherwise entitled. Every reasonable effort should be made to determine the reason 
a participant withdraws prematurely, and this information should be recorded on the appropriate 
page(s) of the case report form (CRF). Participants may be withdrawn from the study for any of 
the following reasons: 
• Participant unable or unwilling to continue 
• Participant’s perceived lack of benefit 
• Participant elects to withdraw informed consent 
• Due to an adverse event 
• Protocol non-compliance 
• Participant is lost to follow up 
• The PI considers that it is in the participant’s best interest not to continue 
participation in the study 
7.4.2. 
Early Discontinuation from Study Drug Administration 
If a participant needs to discontinue study drug, the reason (i.e. due to an SAE, need for an 
excluded medication, etc.) should be documented in the eCRF.  
NOTE: The Medical Monitor should be contacted to discuss whether to continue with planned 
XT-150 dosing in the event that the participant situation changes significantly in the 24 hours 
prior to XT-150 injection such that participant safety is at risk. 

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7.5. 
Replacement of Participants 
After randomization, withdrawn participants will not be replaced. 
7.6. 
Study Termination by Sponsor and Termination Criteria 
The Sponsor reserves the right to terminate an investigational site or this clinical study at any 
time. Reasons for termination may include, but are not limited to, the following: 
• The incidence or severity of AEs in this or other studies of XT-150 indicate a 
potential health hazard to participants 
• Serious or persistent noncompliance by the Investigator with the protocol, clinical 
research agreement, or applicable regulatory guidelines in conducting the study 
• IRB decision to terminate or suspend approval for the investigation or the Investigator 
• Investigator request to withdraw from participation 
• Participant enrollment is unsatisfactory 

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Data from pilot studies in animals showed that saline solutions produce no efficacious benefit in 
a wide variety of pain models. PBS has not demonstrated clinical benefit for pain and is therefore 
suitable for use as a placebo. 
8.2. 
Investigational Product Administration 
Investigational product (XT-150 or placebo) will be administered as two bolus, bilateral intra-
articular injections into the facet joint. The injection will be performed with fluoroscopic 
guidance. 
8.3. 
XT-150 Blinding 
The Investigator, study staff, and participants will be blinded to the treatment administration. The 
unblinded pharmacy will provide ready-to-use syringes, coded by participant number to the 
clinical staff. The Pharmacy will maintain a log in a secure location with the participant number 
and the assigned lot number of the investigational product. Lot numbers are unique to dosage 
strengths. 
8.4. 
Compliance 
Treatment compliance for intra-articular study drugs will be documented in the CRF by 
recording the date, injection time, and whether the dose of study drug was completely injected. 
8.5. 
Previous and Concomitant Medications and Substances 
All pain therapy (both medications and treatments) and all prescription and over-the-counter 
medications and supplements administered within the last month prior to enrollment will be 
documented in the CRF. 
8.5.1. 
Prohibited Medications 
See exclusion criteria (Section 7.2).  
The following treatments are prohibited prior to study drug administration at Day 0 and Day 90: 
• Current treatment with antibiotics or antiviral agents (exception: topical treatments) 
• Current treatment with immunosuppressive agents 
• Current use of systemic steroids (equivalent to >10 mg/day prednisone) 
• Current treatment with anticoagulants, other than low-dose aspirin. Patients, if medically 
feasible, can interrupt anticoagulant therapy by following local medical practice protocol 
for intra-articular injections for patients on anticoagulant, antiplatelet therapy. 
Concomitant medications for pain will be allowed at doses and frequencies prescribed prior to 
the study treatment. In the event a participant requires additional analgesic treatment during 
study participation, he/she should take the protocol-specified rescue medication. Introduction of 
new medications to treat FJOA pain during the study period is prohibited and considered a 
protocol deviation.  

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9. 
STUDY PROCEDURES 
Study procedures should be completed within the windows provided in the Schedule of 
Assessments and Procedures located in Table 1.  
A telephone call documenting safety and efficacy assessments may be used for participants 
unable to physically attend follow up visits due to COVID-19 infection or coronavirus exposure 
concerns. Home services may be employed for blood collections.  
Any nonscheduled procedures required for urgent evaluation of safety concerns take precedence 
over all routine scheduled procedures. 
9.1. 
Screening 
Unless otherwise indicated, screening assessments should be performed within 30 days of 
enrollment. 
• Obtain signed informed consent prior to initiating any study-related assessments or 
procedures 
• Obtain a complete medical history and risk factors (e.g., active malignancy, diabetes 
mellitus, immunosuppression, transplant recipient, trauma, dialysis) and Intensive 
Care Unit admission and discharge (if applicable) 
• Obtain demographics (age, race, gender) 
• Obtain history of all pain medications (prescription and non-prescription) and 
therapies (e.g., physical therapy, acupuncture) and all other medications and 
supplements (prescription and over-the-counter [OTC]) administered within the last 
month prior to enrollment 
• Confirm severe facet arthropathy of lumbar facets as determined by imaging (e.g., 
MRI, CT, X-Ray, etc.) to establish an underlying basis of disease, as determined by 
usual bony and ligamentous signs of osteoarthritis (OA). Use of historical images 
permitted if obtained within the last 12 months. 
• Clinical assessments 
− Conduct complete physical examination, including height and weight (calculate 
body mass index [BMI]) and examination of the injection site 
− Measure vital signs (temperature and the site collected [oral, rectal, temporal, or 
tympanic], heart rate, blood pressure, and respiratory rate) 
− Verify VAS ≥50 prior to lidocaine injection to verify eligibility (see Inclusion 
Criterion #7). A second VAS should be completed post-lidocaine injection to 
verify participant’s reduction in pain is ≥50% (see Inclusion Criterion #5). 
• Laboratory Assessments 
− Obtain blood samples for: 
− Hematology tests (complete blood count [CBC] with differential and platelets 
count),  

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− HIV, Hepatitis B and C serology with reflex 
− Serum pregnancy test for women of child-bearing potential 
− Serum chemistry tests (21) 
• Lidocaine testing for target facet joint for study drug injection: 
− Diagnostic unilateral injection with approximately 0.5 mL lidocaine solution at 
the affected level, as determined by imaging (e.g., MRI, CT, X-Ray, etc.) and 
physical exam, L3-4, L4-5, or L5-S1 (or the three lumbar cephalad to the sacrum 
in the case of patients with a 6th lumbar vertebral body). The injection will be 
performed with fluoroscopic guidance, using the ipsilateral oblique projection. A 
spinal needle will be placed in an intra-articular position, after local anesthesia of 
the skin and subcutaneous tissues. The patient will be observed for 1 hour after 
this injection.  
− Retesting may be performed once at the same level or a different level. If retesting 
is performed on the same day as the initial test, the retest should be separated 
from the initial test by at least 1 hour. 
• Confirm participant qualification by inclusion/exclusion 
9.2. 
Baseline (Day-1 or Day 0) 
Baseline assessments may be completed the day before or day of study drug administration, 
before the XT-150 injection.  
 
  
• Brief physical exam, including examination of the injection site. 
• Obtain any changes from the complete medical history.  
• Record any changes or updates in medications, including pain medications 
(prescription and non-prescription) and therapies (e.g., physical therapy, acupuncture) 
administered since Screening visit. 
• Efficacy assessments 
− VAS score. Verify VAS ≥50. 
− Oswestry Disability Index 
− International Physical Activity Questionnaire (IPAQ) short form 
− SF12 
− Record participant’s response to the OA question: “Considering all the ways that 
facet pain, the pain that brought you into this study, affects you, how are you 
doing today?” on a scale of 1 to 5, 1 being very good (asymptomatic and no 
limitation of normal activities) to 5, very poor (very severe, intolerable symptoms 
and inability to carry out normal activities) 
• Clinical assessments 

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− Measure vital signs (temperature and the site collected [oral, rectal, temporal, or 
tympanic], heart rate, blood pressure, and respiratory rate) 
• Laboratory assessments 
− Obtain serum for analysis of IL-10 protein and anti-IL-10 antibodies 
− Obtain whole blood for plasmid DNA analysis 
• Confirm participant qualification by inclusion/exclusion criteria. Enroll participant 
prior to dosing 
9.3. 
Day 0 
• Before administration of study drug: 
− Confirm that all study criteria are met (inclusion and exclusion) 
− Brief physical exam 
− Injection site examination 
− Record any ongoing medical observations that occurred since Screening visit 
− Record any new AEs since Screening 
− Record any concomitant medications since Screening including prescription, OTC 
and herbal medications. Ensure no excluded medications. 
• Administer study drug (see Section 8 for details on preparation) 
− Aseptic techniques will be used in the preparation and administration of XT-150 
− Injections will be guided by ultrasound, fluoroscopy or equivalent visualization 
− All injections of study drug must be performed by a specialist who is qualified, 
trained, and experienced to perform intra-articular injections to the Facet joint. 
− Examine injection site for infections or reactions 
• Clinical assessments 
− Monitor Participant for approximately for 4 hours for signs of study drug reaction. 
− Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
at least once about 1 hour after injection 
• Laboratory assessments 
− Approximately 4 hours after administration, obtain whole blood for XT-150 
plasmid analysis 
 
 
 
 

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9.7. 
End of Study Visit – Day 270 (±14 days) 
• Clinical assessments 
− Brief physical exam, including height and weight (calculate body mass index 
[BMI]) and examination of the injection site for infections or inflammation  
− Measure vital signs (temperature, heart rate, blood pressure, and respiratory rate) 
• Efficacy assessments 
− VAS score 
− Oswestry Disability Index 
− IPAQ short form 
− SF12 
− Record participant’s response to the question: “Considering all the ways that 
Facet pain, the pain that brought you into this study, affects you, how are you 
doing today?” on a scale of 1 to 5, 1 being very good (asymptomatic and no 
limitation of normal activities) to 5, very poor (very severe, intolerable symptoms 
and inability to carry out normal activities)  
− Record changes in drug regimens or pain therapy 
• Laboratory assessments 
− Obtain blood sample for serum pregnancy test for women of child-bearing 
potential 
− Obtain serum for analysis of anti-IL-10 antibodies 
• Assess, identify, and record any AEs since last visit 
• Record any changes in concomitant medications since screening visit including 
prescription, OTC, and herbal medications. 
 
 

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10. 
ASSESSMENT OF SAFETY 
10.1. 
Safety Parameters 
Safety will be assessed through the evaluation of AEs, vital signs, and serum laboratory data 
according to the Schedules of Assessments and Procedures presented in Table 1 and assessment 
of anti-IL-10 antibodies as described in Section 12. 
10.2. 
Adverse Events 
Medical history will be collected for all participants at the time of informed consent. After 
consent, all adverse events (AEs)/serious adverse events (SAEs) will be collected through the 
last study visit on Day 270. All AEs/SAEs that occur during or after the time of study drug 
treatment will be considered treatment-emergent AEs (TEAEs). The Investigator will assess all 
AEs and SAEs and will record the following information on the appropriate CRF page and SAE 
Report Form (as applicable): 
• Event term 
• Date of onset  
• Date of resolution or stabilization 
• Severity 
• Relationship to study drug  
• Action taken with study medication 
Medically indicated laboratory tests (emergency or unscheduled tests) should be conducted at the 
local laboratory. The Investigator should employ best medical judgment in determining how to 
manage AEs and SAEs. Any questions regarding AE or SAE management should be directed to 
the Medical Monitor. 
10.3. 
Adverse Event Reporting 
The Sponsor has obligations for expedited reporting of SAEs meeting specific criteria to 
worldwide regulatory authorities. Therefore, the Sponsor must be notified immediately regarding 
any SAE that occurs after informed consent.  
All SAEs must be reported to the Medical Monitor or Contract Research Organization (CRO) 
Drug Safety Team within 24 hours of the investigational site’s knowledge of the event. 
All SAEs and discontinuations due to AEs will be reported to the IRB based on the IRB’s 
reporting requirements. 
The study site will transmit a SAE report to the CRO Drug Safety Team by email or facsimile 
(email is preferred method) within 24 hours. Contact details will be provided to all sites. An 
initial report can be made via telephone, but a completed SAE report must still be emailed or 
faxed within 24 hours of the site’s knowledge of the event. The study sites will be provided with 
SAE report forms wherein the following information is requested. 
• Participant identification, Investigator name, and site number 

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• SAE information: event term, onset date, severity, and causal relationship 
• The outcome(s) attributable to the event (i.e., death, a life-threatening AE, inpatient 
hospitalization, prolongation of existing hospitalization, a persistent or significant 
disability or incapacity, or other important medical event[s]) 
• A summary of relevant test results, pertinent laboratory data, and any other relevant 
medical history 
• The first and last dates of study drug administration. NOTE: as this is a double-blind 
study, SAE reports should not indicate specific study drug assignments 
• Indicate if the study drug was discontinued or the study drug administration schedule 
was modified 
• Supplemental information may include the following hospital records: laboratory 
results, radiology reports, progress notes, admission and emergency room notes, 
holding and observation notes, discharge summaries, autopsy reports, and death 
certificates 
In addition, relevant CRF pages should be appended to communicate relevant study drug and 
participant outcome information. The SAE report should be emailed or faxed within 24 hours 
with as much of the above information as available at the time. The following minimum 
information is required for reporting an SAE: participant identification, reporting source, the 
event, and the causality assessed by the Investigator (or medically qualified designee). 
Supplemental information may be transmitted using a follow-up SAE report and should not 
delay the initial report. The Sponsor or designee may contact the investigational site to solicit 
additional information or follow up on the event.  
The Investigator must take all therapeutic measures necessary for resolution of the SAE. Any 
medications or procedures necessary for treatment of the SAE must be recorded on the 
appropriate pages of the participant’s CRF. 
10.4. 
Definitions 
10.4.1. 
Adverse Event 
An AE means 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., a clinically significant abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, and does not imply any 
judgment about causality. An AE can arise with any use of the drug and with any route of 
administration, formulation, or dose, including an overdose. 
Facet Joint Osteoarthritis-related events should not be considered or recorded as AEs or SAEs.  
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated with 
clinical signs or symptoms, or require medical intervention. However, each laboratory 
abnormality (e.g., clinically significant changes detected on hematology, or lab chemistries) 
independent from any underlying medical condition that requires medical or surgical 
intervention, or that leads to interruption of study drug infusion or discontinuation, must be 

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recorded as an AE, or SAE if applicable. If the laboratory abnormality is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than as the 
individual laboratory abnormality. In addition, laboratory abnormalities or other abnormal test 
assessments that are associated with signs or symptoms must be recorded as AEs or SAEs if they 
meet the definition of an AE (or SAE) as described above or in Section 10.4.4. 
10.4.2. 
Suspected Adverse Drug Reaction 
A suspected adverse drug reaction is any AE for which there is a reasonable possibility that the 
drug caused the AE. For the purposes of Investigational New Drug safety reporting, ‘‘reasonable 
possibility’’ means there is evidence to suggest a causal relationship between the drug and the 
AE. Suspected adverse drug reaction implies a lesser degree of certainty about causality than 
adverse reaction, which means any AE caused by a drug. 
10.4.3. 
Life-Threatening AE or Life-Threatening Suspected Adverse Drug Reaction 
An AE or suspected adverse drug reaction is considered ‘‘life threatening’’ if, in the view of 
either the Investigator or Sponsor, its occurrence places the patient or participant at immediate 
risk of death. It does not include an AE or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. 
10.4.4. 
Serious AE or Serious Suspected Adverse Reaction 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening AE – see definition above  
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly/birth defect in the offspring of a participant who received study 
drug 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or participant and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias, or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
10.4.4.1. Serious Adverse Event Definition Clarifications 
• Death is an outcome of an AE, and not an AE in itself 
• All deaths during study drug administration or up to the follow-up (FU) visit on Day 
180, regardless of cause or relationship, must be reported 

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• “Occurring at any dose” does not imply that the participant is actively receiving study 
drug at the time of the event 
• “Life-threatening” means that the participant was at immediate risk of death from the 
event as it occurred. This does not include an event that might have led to death, had 
it occurred with greater severity. 
• Complications that occur during hospitalizations are AEs. If an AE prolongs 
hospitalization, it is a SAE. 
• “Inpatient hospitalization” means the participant has been formally admitted to a 
hospital for medical reasons, for any length of time. This may or may not be 
overnight. It does not include presentation and care within an emergency department 
(although an emergency department visit may define a medically important event, 
which is also considered a SAE). 
• The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms, and other clinical information. In such cases, the diagnosis should be 
documented as the AE or SAE, rather than as the individual signs or symptoms. 
10.4.5. 
Unexpected AE or Unexpected Suspected Adverse Drug Reaction 
An AE or suspected adverse drug reaction is considered “unexpected” if:  
• It is not listed in the Investigator’s Brochure or is not listed at the specificity or 
severity that has been observed  
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if an Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis. 
Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater specificity) if an Investigator’s Brochure listed only cerebral vascular accidents.  
‘‘Unexpected,’’ as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the Investigator’s Brochure as occurring with a class of drugs or as anticipated 
from the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation. 
10.5. 
Adverse Event Classification 
10.5.1. 
Relationship to Investigational Drug 
The Investigator’s assessment of causality must be provided for all AEs (serious and non-
serious) (Table 5). An Investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE. 

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Table 5: 
Guidelines for Assessing Relationship of Event to Study Drug 
Unrelated 
There is little or no chance that the Investigational Product caused the AE; other 
conditions, including concurrent illnesses, progression or expression of the disease 
state, or a reaction to a concomitant medication best explain the event 
Related 
The association of the AE with the Investigational Product is unknown, however, the 
AE is not clearly due to another condition, or a reasonable temporal association exists 
between the AE and treatment administration and, based on the Investigator's clinical 
experience, the association of the AE with the Investigational Product seems likely 
10.5.2. 
Severity 
All AEs will be graded for severity to describe the maximum intensity of the AE based on 
Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) (National Cancer 
Institute, 2017). For purposes of consistency, these intensity grades are defined in Table 6 . 
Table 6: 
Guidelines for Severity Assessments 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
Grade 2 
Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (e.g., preparing meals, shopping for 
groceries or clothes, using the telephone, managing money) 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care activities of 
daily living (bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden) 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to adverse event 
These criteria, in addition to good clinical judgment, should be used as a guide for determining 
the causal assessment. If the event is believed to be unrelated to study drug administration, then 
an alternative explanation should be provided. 
10.6. 
Adverse Event Follow-up 
All unresolved SAEs (“ongoing” at discharge) will be followed by the study staff until resolution 
or deemed stable. 
10.7. 
Adverse Events of Special Interest 
10.7.1. 
Adverse Events of Noted Interest in IL-10 Protein Trials 
Safety will include the following reported IL-10 protein-associated toxicities as defined by 
CTCAE (v5.0). Systemic levels of XT 150 produced IL-10 protein are expected to be more than 
1000-fold lower than when given as a protein solution (Huhn, 1997); and XT-150 will be 
predominately localized to the facet joint space. 
• Grade 1 (unexplained) fever – 38.6°C to 39°C 

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• Grade 2 allergic, cytokine release, or infusion-related reactions - Therapy or infusion 
interruption indicated but responds promptly to symptomatic treatment (e.g., 
antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for 
≤24 hours 
• Grade 2 injection site reaction - Pain; lipodystrophy; edema; phlebitis 
• Grade 2 neutropenia - <1500 to 1000/mm3; <1.5 to 1.0 x109/L 
10.7.2. 
Localized Signs of Infection or Inflammation at the Injection Site 
Events that, in the opinion of the Investigator, may represent localized signs of infection or 
inflammation at the XT-150 injection site (e.g., pain, erythema, swelling, pruritus, warmth, 
hematoma, induration) must be recorded as AEs on the CRF. In general, these events will be 
temporally related to the injection. 
10.8. 
Toxicity Management 
The Investigator should employ best medical judgment in determining how to manage AEs. Any 
questions regarding AE management should be directed to the Medical Monitor. 
10.9. 
Risks for Women of Childbearing Potential or During Pregnancy 
The risks of XT-150 administration during pregnancy have not been evaluated. Male and female 
participants who are heterosexually active and not surgically sterile must agree to use effective 
contraception, including abstinence, for the duration of the study. 
During the study, participants should be instructed to contact the Investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual cycle). The Investigator must 
immediately notify the Medical Monitor or CRO Drug Safety Team of any female participant or 
female partner of any male participant that becomes pregnant at any time during study 
participation. All pregnancies must be reported to the Medical Monitor or CRO Drug Safety 
Team using the Pregnancy Report Form within 24 hours of the investigational site’s knowledge 
of the event. The Medical Monitor/CRO will ask the site to obtain a separate consent from the 
female participant (or female partner of a male participant) using an IRB-approved template in 
order to follow-up periodically during the pregnancy for ongoing health and safety information 
through the end of the pregnancy, as applicable.  
Any anomalies, complications, abnormal outcomes, or birth defect(s) observed in the child must 
be reported as a SAE using the SAE Report Form within 24 hours of the investigator or study 
personnel’s first knowledge. While elective and uncomplicated induced abortion not required for 
medical reasons does not constitute an AE or SAE (even if the patient or patient’s partner is 
hospitalized to undergo abortion), spontaneous abortion is considered a fatal event and must be 
reported as an AE and SAE, as appropriate. 
All pregnancies will be reported to the IRB based on the IRB’s reporting requirements. 

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12. 
ASSESSMENT OF ANTI-IL-10 ANTIBODIES 
Presence of anti-IL-10 antibodies in serum will be assessed. Whole blood for detection of anti-
IL-10 antibodies will be drawn at Baseline, then on Days 7, 14, 30, 60, 90, 180, and 270 then 
processed to serum. Testing will be conducted following completion of the study. 
Procedures for collection, storage, and shipping of immunogenicity samples are described in the 
study Laboratory Manual. 

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13. 
ASSESSMENT OF XT-150 PLASMID DNA BIODISTRIBUTION 
Presence of plasmid DNA in whole blood will be assessed. Whole blood for detection of plasmid 
DNA will be drawn at Baseline, Day 0 + 4 hours, then on Days 7, 14, and 30. Testing will be 
conducted following completion of the study. 
Procedures for collection, storage, and shipping of plasmid DNA samples are described in the 
study Laboratory Manual. 

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15. 
INVESTIGATOR REQUIREMENTS 
15.1. 
Protocol Adherence  
The Investigator must adhere to the protocol as detailed in this document and agree that the 
Sponsor must approve any change to the protocol before seeking approval from the IRB. The 
Investigator will be responsible for enrolling only those participants who have met the protocol 
inclusion and exclusion criteria. 
15.1.1. 
Investigator or Designee Experience 
The Investigator or Investigator’s designee is required to be qualified, trained, and experienced 
in the administration of study drug by intra-articular injection. 
15.2. 
Case Report Forms 
The CRF will be supplied by the Sponsor or designee for the recording of all information and 
study data as specified by this protocol. All CRFs must be completed by trained study personnel. 
The Investigator is responsible for ensuring that the CRF data are entered and completed in a 
timely manner. 
Once all data queries and issues have been resolved for each participant, the Investigator will 
electronically sign each participant’s CRF to attest to the accuracy of the data. 
15.3. 
Source Document Maintenance 
Source documents are defined as documentation related to original observations and activities of 
a clinical investigation. Source documents may include, but are not limited to, study progress 
notes, study- or participant-specific e-mail correspondence, computer printouts, laboratory data, 
and recorded data from automated instruments. All source documents produced in this study will 
be maintained by the Investigator and made available for inspections by the Sponsor and by 
regulatory authorities. The original signed ICF (and any updates, if appropriate) for each 
participating participant shall be filed with records kept by the Investigator, and a copy shall be 
given to the participant. 
A telephone call documenting safety and efficacy assessments may be used for participants 
unable to physically attend follow up visits due to COVID-19 infection or corona virus exposure 
concerns. Participant responses will be captured in source documents, including circumstances 
for use of telephone follow up. 
15.4. 
Study Monitoring Requirements 
An authorized Sponsor representative will conduct site visits to inspect study data, participants’ 
medical records, and CRFs in accordance with International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, GCPs, and the 
foreign regulations and guidelines, as applicable. A study monitor will be utilized for monitoring 
ongoing drug accountability and adherence to protocol procedures. 
The Investigator will allow representatives of the Sponsor and regulatory authorities to inspect 
facilities and records relevant to this study. 

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15.5. 
Study Completion 
The Sponsor requires the following data and materials before a study can be considered complete 
or terminated: 
• Laboratory findings, clinical data, and study test results from Screening throughout 
the study through Day 270 
• CRFs (including data queries) properly completed by appropriate study personnel and 
signed and dated by the Investigator 
• Copies of complete drug accountability records (drug inventory log and an inventory 
of returned or destroyed clinical material) 
• Copies of protocol amendments and IRB/ approval and notification, if appropriate 
• A summary of the study prepared by the Investigator (an IRB summary letter is 
acceptable) 

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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Written standard operating procedures (SOPs) will be followed to ensure that the study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable regulatory requirements. Quality control will be applied to 
each stage of data handling. Regular monitoring, as defined in ICH GCP, Section 1.8, “The act 
of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and 
reported in accordance with the protocol, SOPs, GCP, and the applicable regulatory 
requirement(s)”, will be conducted throughout the conduct of the study. 
The purpose of monitoring is to verify that: 
• Rights and well-being of the human participants are protected 
• The reported study data are accurate, complete, and verifiable from source documents 
• The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirements 
• Monitoring is an integral role in the quality control of a clinical trial and is designed 
to ensure and verify the quality of the study 
To fulfill the Quality Assurance requirements of GCP, audits will be conducted to assess and 
assure the reliability and integrity of a study’s quality control systems and recognized standards. 
The purpose of an audit is to: 
• Ensure participant safety 
• Assure compliance to study protocol procedures, regulatory requirements, and SOPs 
• Assure data quality 

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17. 
PROTECTION OF HUMAN PARTICIPANTS 
This study will be conducted in compliance with the ICH Technical Requirements for 
Registration of Pharmaceuticals for Human Use E6 GCP: Consolidated Guidelines, the ethical 
principles of the Declaration of Helsinki, Food and Drug Administration (FDA) GCP guidelines, 
and any additional national or IRB-required procedures, particularly those related to the Corona 
Virus Disease 2019 (COVID-19) pandemic. 
17.1. 
Informed Consent 
This study will be conducted in compliance with ICH E6 GCP: Consolidated Guidelines 
pertaining to informed consent. Participants will give written consent to participate in the study 
at the first visit, prior to initiation of any study-related procedures, after having been informed 
about the nature and purpose of the study, participation and termination conditions, risks, and 
benefits. If a participant is unable to provide written informed consent, the participant’s legally 
acceptable representative may provide written consent, as approved according to institution-
specific guidelines. The ICF must be signed and dated by the participant, or the participant’s 
legally authorized representative, prior to study participation. A copy of the ICF must be 
provided to the participant or the participant’s legally authorized representative. If applicable, it 
will be provided in certified translation for non-English-speaking participants. Signed consent 
forms must remain in the participant’s study file and be available for verification by Sponsor at 
any time. 
17.2. 
IRB Approval 
This protocol, the ICF, and all relevant supporting data must be submitted to the IRB for 
approval. The protocol, ICF, and any advertisement used to recruit study participants must be 
approved by the IRB. Approval by the IRB of the protocol and ICF must be obtained before the 
study may be initiated. 
The Investigator is responsible for informing the IRB of any changes made to the protocol, and 
to advise them, at least once a year, about the progress of the study. The Investigator is also 
responsible for notifying the IRB of any significant AEs or other important events that occur 
during the study based on the IRB’s reporting requirements. 

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18. 
DATA HANDLING AND RECORD KEEPING 
Training sessions, regular monitoring of Investigators by Sponsor-designated personnel, 
instruction manuals, data verification, crosschecking, and data audits will be performed to ensure 
the quality of all study data. Investigator meetings will be performed to train Investigators and 
other study personnel in the appropriate collection of study data. The Sponsor or designee will 
review and validate study data according to standard procedures. 
It will be the responsibility of the Investigator to ensure that the essential documents are 
available at the Investigator or institutional site. Any or all of these documents may be 
participant to, and should be available for, monitoring by the Sponsor or inspection by the 
regulatory authorities as defined in the monitoring plan. 
18.1. 
Direct Access to Source Data/Documentation 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission to national or international registration. If required, these authorities will be provided 
with the name of the Investigator and his or her address, qualifications, and extent of 
involvement. It is understood that the Investigator is required to provide Sponsor with all study 
data, complete reports, and access to all study records. 
Data generated by this study must be available for inspection by any regulatory authorities, by 
Sponsor, and by the IRB as appropriate. At a participant’s request, medical information may be 
given to his or her personal physician or other appropriate medical personnel responsible for his 
or her welfare. Medical information obtained from participants during the course of this study is 
confidential and disclosure to third parties other than those noted above is prohibited. 
18.2. 
Study Drug Accountability 
All supplies of XT-150 study drug required for completion of this study will be provided by the 
Sponsor. It is the responsibility of the Investigator and study staff to ensure that a current record 
of drug inventory and drug accountability is maintained. Inventory and accountability records 
must be readily available for inspection and are open to inspection at any time by applicable 
regulatory authorities. 
18.3. 
Retention of Records 
Essential clinical documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the investigational product and shipment and delivery of the drug for 
investigational use is discontinued. These documents should be retained for a longer period, 
however, if required by the applicable regulatory requirements of specific ICH- and non-ICH 
countries, or by an agreement with the Sponsor. The Sponsor will inform the 
Investigator/institution as to when these documents no longer need to be retained. 

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19. 
FINANCING AND INSURANCE 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 

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20. 
PUBLICATION POLICY 
The data generated in this clinical study are the exclusive property of the Sponsor and are 
confidential. Authorship on any publication of the results from this study will be based on  

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21. 
REFERENCES 
References available upon request 
Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical 
practice. Psychiatry (Edgmont). 2007 Jul;4(7):28-37. 
Chernoff AE, Granowitz EV, Shapiro L, Vannier E, Lonnemann G, Angel JB, Kennedy JS, 
Rabson AR, Wolff SM, Dinarello CA. A randomized, controlled trial of IL-10 in humans. 
Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995 May 
15;154(10):5492-9. 
FDA, Guidance for Industry: Considerations for Plasmid DNA Vaccines for Infectious Disease 
Indications. 2007.  
Ferraro B, Morrow, MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. Clinical applications of 
DNA vaccines: current progress. Clin Infect Dis. 2011 Aug 1;53(3):296-302. 
Gôrecki DC. "Dressed-up" naked plasmids: emerging vectors for non-viral gene therapy. Discov 
Med. 2006 Oct;6(35):191-7.  
Huhn RD, Radwanski E, Gallo J, Affrime MB, Sabo R, Gonyo G, Monge A, Cutler DL. 
Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers. 
Clin Pharmacol Ther. 1997 Aug;62(2):171-80. 
Huhn RD, Radwanski E, O'Connell SM, Sturgill MG, Clarke L, Cody RP, Affrime MB, Cutler 
DL. Pharmacokinetics and immunomodulatory properties of intravenously administered 
recombinant human interleukin-10 in healthy volunteers. Blood. 1996 Jan 15;87(2):699-705. 
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 
Dec;16(4):494-502. 
Kim, B.R., Lee, J.W., Lee, E. et al. Intra-articular facet joint steroid injection–related adverse 
events encountered during 11,980 procedures. Eur Radiol 30, 1507–1516 (2020). 
Kohn MD, Sassoon, AA, Fernando ND. Classifications in Brief: Kellgren-Lawrence 
Classification of Osteoarthritis. Clin Orthop Relat Res. 2016 Aug ;474 (8):1886-93. 
Milligan, ED, Sloane EM, Langer SJ, Cruz PE, Chacur M, Spataro L, Wieseler-Frank J, 
Hammack SE, Maier SF, Flotte TR, Forsayeth JR, Leinwand LA, Chavez R, Watkins LR. 
Controlling neuropathic pain by adeno-associated virus driven production of the anti-
inflammatory cytokine, interleukin-10. Mol Pain. 2005 Feb 25;1:9. 
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 
receptor. Annu Rev Immunol. 2001;19:683-765. 
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) (version 
5.0). 2017. 
Prazeres DMF, Monteiro GA. Plasmid Biopharmaceuticals. Microbiol Spectr. 2014 Dec;2(6). 
doi: 10.1128/microbiolspec.PLAS-0022-2014. 
Sawada M, Suzumura A, Hosoya H, Marunouchi T & Nagatsu T. Interleukin-10 inhibits both 
production of cytokines and expression of cytokine receptors in microglia. J Neurochem 1999 
Apr;72(4):1466-71. 

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van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-
refractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology. 1997 
Aug;113(2):383-9. 
Xu L, Anchordoquy T. Drug delivery trends in clinical trials and translational medicine: 
challenges and opportunities in the delivery of nucleic acid-based therapeutics. J Pharm Sci. 
2011 Jan;100(1):38-52. 

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APPENDIX 1. CLINICAL LABORATORY TESTS 
Hematology 
• Hemoglobin 
• hematocrit  
• total and differential leukocyte count 
• red blood cell count 
• platelet count 
Serum Chemistry 
• bilirubin (total and direct) 
• alkaline phosphatase (ALP) 
• aspartate aminotransferase (AST) 
• alanine aminotransferase (ALT) 

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APPENDIX 2. PROTOCOL SIGNATURE PAGE 
I have read and understand the current version of protocol XT-150-1-0302 and the current 
Investigator’s Brochure. I agree to the following: 
1. To conduct the trial in compliance with GCP, with applicable regulatory requirement(s), 
with the protocol agreed to by the Sponsor and given approval/favorable opinion by the 
IRB. 
2. To comply with procedures for data recording and reporting 
3. To permit monitoring, auditing, and inspection by the Sponsor, its designated 
representatives, and regulatory authorities  
4. To retain the essential documents in the Investigator/institution files until the Sponsor 
informs the Investigator or institution that these documents are no longer needed 
 
INVESTIGATOR SIGNATURE: 
 
 
_____________________________________/___________________________ 
Investigator Signature  
 
 
 
 
 
 
Date 
 
 
_____________________________________  
Investigator Name 
 
 
_____________________________________  
Site Name  
 
 
_____________________________________  
Site Address