Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain - Dose escalation

Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain.

Subjects for whom replacement knee surgery is recommended will be enrolled in the study. A single injection of a DNA plasmid with a variant Interleukin-10 (IL-10) transgene will be injected into the synovial capsule of the knee.

This is a first in human, dose-range, safety and efficacy study.

Inclusion Criteria:

1. Male or female, between 18 and 90 years of age, inclusive. Women who are not of child-bearing potential in the same age range.

2. Sufficiently severe OA of knee to require/have recommended knee replacement surgery or be unsuitable for knee replacement surgery or be unsuitable for knee replacement surgery based on co-morbidities or orthopedic considerations; be free of local or intra-articular infection.

3. Symptomatic disease because of osteoarthritis, defined as one or more of the following Verbal Numerical Rating Scale (VNRS) scores:

   1. a worst pain of at least 7 at any time during the preceding week (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine").
   2. a worst stiffness of at least 7 at any time during the preceding week (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine").

4. Stable analgesic regimen during the 4 weeks prior to enrollment.

5. Inadequate pain relief (mean >5 mean on Brief Pain Inventory-Severity Scale) from prior therapies lasting 3 months.

6. In the judgment of the Investigator, acceptable general medical condition

7. Life expectancy >6 months

8. Male participants who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study and for 3 months after the study is completed.

9. Have suitable knee joint anatomy for intra-articular injection

10. Willing and able to return for the follow-up (FU) visits

11. Able to reliably provide pain assessment

12. Able to read and understand study instructions, and willing and able to comply with all study procedures

Exclusion Criteria:

1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose
2. Scheduled knee replacement within 4 months; participant agrees not to schedule a knee replacement appointment within 4 months of study treatment
3. History of rheumatoid arthritis of the knee
4. High peri-operative risks which in the judgment of the investigator preclude a safe knee injection procedure (e.g., poorly controlled diabetes, cardiac inadequacy such as NYHA class > II, G4 glomerular filtration rate [eGFR < 30 mL/min by Cockcroft-Gault])
5. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/day prednisone] or other strong immunosuppressant)
6. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months.
7. Currently receiving systemic chemotherapy or radiation therapy for malignancy
8. 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)
9. Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion indicated), uncontrolled coagulopathy (Grade 1, prolonged activated partial prothrombin time (aPTT) > upper limit of normal (ULN) to 1.5xULN), or bleeding diathesis, Grade 1 white cell counts (lymphocytes \

All data will be de-identified in a clinical trial database

Unblinded pharmacy provides injection preparation for blinded administration