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

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.

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