Follow on Extension of XT-150-1-0201

Study Overview
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Brief Summary
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XT-150 safety and efficacy in severe osteoarthritic pain.

Detailed Description
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XT-150-1-0201 Extension: Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain. Participants in this study will have been enrolled in the 0201 study and qualify for an intra-articular injection of XT-150 into the osteoarthritic knee. The study will assess XT-150 safety, tolerability, and efficacy in participants who received placebo in the 0201 study, or have a second qualifying knee, or a second injection into the same knee that was treated in 0201.

Official Title
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XT-150-1-0201 Extension: Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: XT-150


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Qualified and participated in clinical study XT-150-1-0201. Participant was assigned to placebo, or Participant elects to have XT-150 administered to the XT-150-untreated knee that qualified under XT-150-1-0201 criteria, or Participant had inadequate pain relief and elects to receive a second injection to the same knee treated on clinical study XT-150-1-0201 Sufficiently severe OA of knee to require/have recommended 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. Symptomatic disease because of osteoarthritis, defined as a Verbal Numerical Rating Scale (VNRS) scores of 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). Stable analgesic regimen during the 4 weeks prior to enrollment. Inadequate pain relief (minimum ≥ 5 mean on Brief Pain Inventory-Severity Scale) lasting more than 3 months. In the judgment of the Investigator, acceptable general medical condition Life expectancy >6 months 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. Have suitable knee joint anatomy for intra-articular injection Willing and able to return for the follow-up (FU) visits Able to reliably provide pain assessment 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 Scheduled knee replacement within 4 months; participant agrees not to schedule a knee replacement appointment within 4 months of study treatment History of rheumatoid arthritis of the knee or gout. 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]) Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/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 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 <LLN - 800/mm3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 109 /L) 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. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit Women of child-bearing potential Use of any investigational drug, other than XT-150, 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

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose from study XT-150-1-0201<br>Open label administration of the highest dose in the earlier study, in which all doses were well tolerated | Biological: XT-150<br>* IL-10 transgene DNA plasmid injected into the knee synovial capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Clinical Pathology, adverse events | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal Numeric Rating Score | Pain scale from 1 to 10, 10 being worst possible | 6 months | 
| KOOS | Osteoarthritis pain, symptoms, impact on daily living, and quality of life. Subset scores are calculated such that 100% is normal function | 6 months | 
| Brief Pain Inventory | Pain and interference on daily living functions. Scales ranges from 0 to 10, with 10 being the worst | 6 months | 
| Clinical Global Improvement | 0 - 7 Scale, 4 and below indicate no change or improvement. Over 4 indicates degrees of worsening | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokines, Anti-inflammatory, Pain, Inflammation