Efficacy and Safety of XT-150 in Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This is a Phase 2 safety and efficacy study of XT-150 in adult participants experiencing moderate to severe pain due to osteoarthritis of the knee.

Detailed Description
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In this Phase 2 study, Baseline (Day 0) confirmation of study eligibility will be completed the day before or day of study drug administration. Study drug will be administered by intra-articular (IA) injection into the joint space of the index knee (knee selected for treatment). Up to 270 participants will be randomly enrolled into 1 of 6 treatment sequences (45 participants/ group). Treatment Groups: 0.15 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL) 0.15 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL) 0.45 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL) 0.45 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL) Placebo (1mL), 0.15 mg/mL XT-150 (1mL) Placebo (1mL), 0.45 mg/mL XT-150 (1mL) The study will be conducted in 2 stages, A and B. Participants will be randomized at Day 0 to a treatment regimen, one treatment assignment for Stage A and one treatment assignment for Stage B: Stage A (Up to Day 180): Participants will receive placebo, 0.15 mg/mL XT-150 or 0.45 mg/mL XT-150 to the index knee at Day 0. Stage B (Day 180 to Day 360): Participants will have the option to receive a pre-randomized dose (XT-150 0.15 mg/mL or 0.45 mg/mL) to the index knee anytime between Day 180 and Day 330. Final assessments will be 12 months after the first IA dose.

Official Title
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A Double-Blind, Placebo-Controlled Assessment of the Tolerability and Efficacy of XT-150 for the Treatment of Moderate to Severe Pain Due to Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic disease due to osteoarthritis, defined as a WOMAC Pain score ≥ 8 (worst possible = 20) Focused Analgesia Selection Test will be used to determine whether patients can report pain with sufficient consistency to enter the clinical trial Males and females between 45 and 85 years of age, inclusive Kellgren-Lawrence grading of 2 or 3 within the last 6 months Stable analgesic regimen during the 4 weeks prior to enrollment In the judgment of the Investigator, acceptable general medical condition Life expectancy >6 months 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 Have suitable knee 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: Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose Previously received XT-150 injection(s) Scheduled partial or complete knee replacement within 6 months; participant agrees not to schedule a knee replacement during Stage A of the study History of knee arthroplasty on the Index Knee, i.e., selected for study injection(s) History of rheumatoid arthritis or other inflammatory disease History of immunosuppressive therapy; systemic steroids in the last 3 months Received knee injection with hyaluronic acid or stem-cells in the last 6 months Knee injection of glucocorticoid in the last 3 months Current treatment with systemic immunosuppressive (systemic corticosteroid therapy or other strong immunosuppressant) 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) 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/mm^3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm^3; <LLN - 1.5 x 109 /L), LLN=Lower Limit Normal Range Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus 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 anticoagulant or anti-platelet treatment (e.g., warfarin, heparins, factor X inhibitors, clopidogrel, prasugrel, ticagrelor, or dipyridamole). Low-dose (≤ 325 mg/day) aspirin is permitted 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 3 months 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 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: 45 Years
Maximum Age: 85 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: Stage A: 0.15 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150<br>Low dose active in Stage A and Stage B | Biological: XT-150<br>* plasmid DNA<br>|
| Experimental: Stage A: 0.15 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150<br>Low dose active in Stage A, high dose active in Stage B | Biological: XT-150<br>* plasmid DNA<br>|
| Experimental: Stage A: 0.45 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150<br>High dose active in Stage A, low dose active in Stage B | Biological: XT-150<br>* plasmid DNA<br>|
| Experimental: Stage A: 0.45 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150<br>High dose active in Stage A and Stage B | Biological: XT-150<br>* plasmid DNA<br>|
| Placebo Comparator: Stage A: Placebo, Stage B: 0.15 mg/mL XT-150<br>Inactive comparator in Stage A, low dose active in Stage B | Biological: XT-150<br>* plasmid DNA<br>Drug: Placebo<br>* Placebo is a sterile phosphate-buffered saline<br>|
| Placebo Comparator: Stage A: Placebo, Stage B: 0.45 mg/mL XT-150<br>Inactive comparator in Stage A, high dose active in Stage B | Biological: XT-150<br>* plasmid DNA<br>Drug: Placebo<br>* Placebo is a sterile phosphate-buffered saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage A: Number of participants achieving 30% improvement from Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) pain score | WOMAC pain score will be obtained from Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value. | Up to Day 180 | 
| Stage A: Change from Baseline in WOMAC Pain Score at Day 180 |  | At Day 180 | 
| Stage A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) |  | Up to Day 180 | 
| Stage B: Number of participants with AEs and SAEs |  | Up to Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage B: Change from Baseline in WOMAC Pain Score at Day 360 |  | At Day 360 | 
| Stage A and Stage B: Change from Baseline in WOMAC function score | WOMAC function score will be obtained from KOOS questionnaire which is a is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The function dimension category asks about the degree of difficulty in doing 17 activities. The score ranges from 0 (normal function) to 170 (severely limited function); higher score indicates worse outcomes. Baseline is defined as the Day 0 value. | Up to Day 360 | 
| Stage A and Stage B: Change from Baseline in Brief Pain Inventory (BPI) of Interference score | The BPI is a self-administered questionnaire for participants to rate the degree to which their pain interferes with common dimensions of feeling and function. The 7 pain interference items will be rated on 0-10 scale. Total interference score ranges from 0 (does not interfere) to 10 (completely interferes); higher score indicates worse outcomes. | Up to Day 360 | 
| Stage A and Stage B: Change from Baseline in Patients Overall Assessment (POA) | The POA is a self-administered questionnaire that records participants' responses to the question Considering all the ways the OA in your knee 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). Higher score indicates worse symptoms. | Up to Day 360 | 
| Stage A and B: Number of participants with presence of anti-interleukin (IL)-10 antibody |  | Up to Day 360 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Pain, Interleukin, Gene Therapy, plasmid DNA