Safety and Efficacy of XT-150 for Facet Joint Osteoarthritis Pain

Study Overview
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Brief Summary
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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, also known as 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. 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. Lumbar [L]3-4, L4-5, or L5-Sacrum [S]1) as determined by imaging (e.g., Magnetic resonance imaging [MRI], Computed tomography [CT]), X-ray, etc.) and physical exam. Up to 72 participants will be randomized to placebo or one of two dose treatment groups (24 participants per treatment group). 0.15 mg XT-150 (1.0 milliliter [mL] total delivered by two 0.5 mL injections) 0.45 mg XT-150 (1.0 mL total delivered by two 0.5 mL injections) Placebo (Sterile saline) (1.0 mL total delivered by two 0.5 mL injections)

Official Title
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A Placebo-controlled, Double-blind Evaluation of Safety, Tolerability, and Efficacy of XT- 150 for the Treatment of Facet Joint Osteoarthritis Pain

Conditions
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Back Pain, Facet Joint Pain, Inflammation

Intervention / Treatment
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* Biological: XT-150
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are required to meet ALL of the following inclusion criteria: Male or female, between 18 and 90 years of age, inclusive. 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. 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 participant. LBP (Low Back Pain) worsened by activity or motion of region Have had a positive diagnostic facet pain block with lidocaine; admittance if participant gains 50% relief of pain within 30 minutes of test injection 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. 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). 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. Inadequate pain relief with prior therapies lasting 3 months or more. In the judgment of the Investigator, acceptable general medical condition 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 Have suitable facet joint anatomy for intra-articular injection Willing and able to return for the follow-up (FU) visits 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: Hypersensitivity, allergy, or significant reaction to lidocaine or any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose Facet injection with corticosteroid in the past 6 months Lumbar medial branch nerve ablation (e.g., by radiofrequency technique) within the past 12 months Prior lumbar fusion surgery Prior or existing medial branch nerve stimulation device (e.g., Mainstay device) 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 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.) Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10 milligrams per day {mg/day} prednisone] or other strong immunosuppressant) History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months. Currently receiving systemic chemotherapy or radiation therapy for malignancy 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) Severe anemia (Grade 3; hemoglobin <8.0 grams per deciliter [g/dL], <4.9 millimoles per liter [mmol/L], <80 g/L; transfusion indicated), Grade 1 white cell counts (lymphocytes <Lower limit of normal [LLN] - 800/cubic millimeters [mm^3]; <LLN - 0.8 x 10^9/L, neutrophils <LLN - 1500/mm^3; <LLN - 1.5 x 10^9/L) Positive serology with reflex for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus within 4 weeks of commencing the study Significant neuropsychiatric conditions, dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments) Current treatment with anticoagulants, other than low-dose aspirin. Participants, if medically feasible, can interrupt anticoagulant therapy by following local medical practice protocol for intra-articular injections for participants on anticoagulant, antiplatelet therapy. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.15mg XT-150<br>0.15mg XT-150 administered in 1.0 mL total delivered by two 0.5 mL injections on Day 0 and Day 90. | Biological: XT-150<br>* XT-150 is a plasmid Deoxyribonucleic acid (DNA) formulated in buffered, D mannose saline solution.<br>|
| Experimental: 0.45mg XT-150<br>0.45mg XT-150 administered in 1.0 mL total delivered by two 0.5 mL injections on Day 0 and Day 90. | Biological: XT-150<br>* XT-150 is a plasmid Deoxyribonucleic acid (DNA) formulated in buffered, D mannose saline solution.<br>|
| Placebo Comparator: Placebo<br>Placebo administered in 1.0 mL total delivered by two 0.5 mL injections on Day 0 and Day 90. | Biological: Placebo<br>* Phosphate-buffered saline for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting serious adverse events (SAEs) and non-SAEs |  | Up to Day 284 | 
| Number of participants reporting abnormal hematology and chemistry parameters, physical examination, and vital signs |  | Up to Day 284 | 
| Change from Baseline in pain intensity using 0-100 Visual Analog Scale (VAS) | The VAS is 0-100 scale which will be administered to participants via Electronic Patient Reported Outcome (ePRO) at each study visit. The participant will record his/her facet pain level on a scale from 0 (no pain) to 100 (worst pain). Higher scores indicate worse pain intensity. | Baseline and at Day 270 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a >30%, >50% or >75% reduction in pain parameters from Baseline |  | Up to Day 284 | 
| Change from baseline in Oswestry Disability Index (ODI) scores | The Oswestry Disability Index (ODI) is a 10-item questionnaire to quantify disability for acute or chronic low back pain. Each question is scored on a scale of 0 (least amount of disability) to 5 (most severe disability). Higher scores indicate severe disability. | Baseline and up to Day 284 | 
| Change from baseline in Patient Global Assessment (PGA) scores | PGA is used to assess the current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). Higher score indicates worse symptoms. | Baseline and Up to Day 284 | 
| Change from baseline in International Physical Activity Questionnaire (IPAQ short form) scores | The globally standardized and validated IPAQ - short form is used to measure self-reported physical activity levels. Four metabolic equivalent tasks (MET) - vigorous, moderate, walking and sitting were included to obtain the physical activity levels from the participants. A higher MET value indicates a higher physical activity level. | Baseline and Up to Day 284 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FJOA, Facetogenic Pain, Intra-articular Injection