Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren/Lawrence Grade 2 or 3 OA of the Knee

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, multi-center, phase 3 study to determine the efficacy and safety of TG-C in subjects with Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee, Osteoarthritis Research Society International (OARSI) medial joint space narrowing (JSN) Grade 1 or 2 of the knee joint. TG-C is to be administered by a single intra-articular injection to the damaged joint area via ultrasound guidance. Patients will be followed for 24 months for safety and efficacy.

Detailed Description
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This protocol is designed to assess the safety and efficacy of TG-C in treating symptoms of osteoarthritis of the knee and determining disease modifying effects of TG-C. This study is intended for the treatment of patients with K&L Grade 2 and 3 osteoarthritis and OARSI JSN Grade 1 and 2. Assessments will be made on both the symptomatic effects of pain (VAS), function (WOMAC), and Quality of Life (SF-12) as well as the physical effects (JSW, MRI evaluations of whole knee joint organ tissues and structure) and biochemical biomarkers. This is a placebo-controlled study, TG-C will be compared to normal saline as a control. Additionally, this protocol is designed to evaluate the safety of TG-C. Safety will be evaluated by observation of the injection site for irritation or other effects, the incidence and severity of adverse events, and changes in physical examination findings, radiographic criteria, and laboratory tests. Patients will be followed for 24 months for both safety and efficacy with annual cancer surveillance questionnaires through 15 years post dose for subjects who do not enroll in the Long Term Safety study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee

Conditions
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Degenerative Osteoarthritis

Intervention / Treatment
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* Biological: TG-C
* Biological: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 40 or older BMI between 18.5 and 40 KL Grade 2 or 3 knee OA OARSI Grade 1 or 2 medial JSN Pain >= 40 on VAS scale Written informed consent Using birth control Exclusion Criteria: Knee symptoms that result in difficulty or inability to walk Knee effusion >2+ Has Grade 3 OARSI JSN MRI exam indicates fracture or tumor Has a positive result on RCR testing at screening Has taken NSAIDS with 14 days of baseline Has taken steroidal anti-inflammatory or biologic therapy medication within 2 months of baseline Chronic (>21 days) narcotic use Recent history (within 1 year) of drug or alcohol abuse Pregnant or lactating Has received injection to target knee within 2 months prior to study entry History of various disorders of the knee including but not limited to rheumatoid arthritis, psoriatic arthritis, autoimmune disorder, chondrocalcinosis, gout, hemochromatosis, villonodular synovitis, or synovial chondromatosis Severe hip osteoarthritis ipsilateral to the target knee Ongoing infectious disease including but not limited to HIV, HTLV-1, VSV-G, HBV, or HCV. Clinically significant congestive heart failure, hepatic disease, kidney disease, adrenal insufficiency, acromegaly, uncontrolled hyper- or hypothyroidism, or non-specified uncontrolled endocrine disorder. Uncontrolled diabetes based on a HbA1c > 8% at screening. Documented active malignancy within the last 5 years except for basal cell carcinoma, squamous cell carcinoma, and benign pigmented nevi.

Ages Eligible for Study
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Minimum Age: 40 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 |
| --- | --- |
| Active Comparator: Active Treatment (TG-C)<br>TG-C at 3 x 10e7 cells per single 2 mL intraarticular injection | Biological: TG-C<br>* 2 mL injection of non-transduced human chondrocytes and irradiated transduced human GP2-293 cells expressing TGF-B1<br>* Other names: TissueGene-C;|
| Placebo Comparator: Placebo Control (Normal Saline)<br>Normal saline, single 2 mL intraarticular injection | Biological: Placebo Control<br>* 2 mL normal saline intraarticular injection<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Function as Assessed by the Western Ontario and McMaster Universities Index (WOMAC) | Assessment of change from baseline in target knee function using the WOMAC Osteoarthritis Index. The WOMAC is a proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee including pain, stiffness, and physical functioning of the joints. The response to the questions is in the form of a checked box associated with the response; None, Mild, Moderate, Severe and Extreme. | 12 months | 
| Change in Knee Pain as Assessed by VAS | Assessment of change from baseline in target knee pain using the Visual Analog Scale (VAS). The VAS is a method for the assessment of the intensity of pain. The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from 0 or no pain to 100 very severe pain. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCS of the SF-12 Questionnaire | Evaluation of the change from baseline in physical component score (PCS) of the SF-12v2 questionnaire. | 12 months | 
| Health Assessment Questionnaire Disability Index | Evaluation of the change from baseline in the disability index of the Health Assessment Questionnaire (HAQ-DI) | 12 months | 
| MRI Assessment of Target Knee | Assessment of knee organ tissues and structure by comparing change in MRI scoring using WORMS and partial MRI Osteoarthritis Knee Score (MOAKS) | 12 months | 
| WOMAC Total Score | Evaluation of the efficacy of TG-C with regard to knee function via WOMAC total score | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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knee