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

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 KL 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.

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

- WOMAC score <=70 for target knee

- Written informed consent

- Using birth control

Exclusion Criteria:

- Knee symptoms that result in difficulty or inability to walk

- Knee effusion >2+

- Has Grade 0 OARSI JSN or atrophic OA

- Has a score of >=5 on the cartilege feature of the WORMS at Screening

- 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 medication within 2 months of baseline

- Currently using topical analgesics on target knee

- 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

- Is contraindicated or cannot undergo for 3 Tesla (3T) MRI

- History of various disorders of the knee including but not limited to rheumatoid
arthritis, psoriatic arthritis, autoimmune OA, chondrocalcinosis, gout,
hemochromatosis, villonodular synovitis, or synovial chondromatosis

- Severe hip osteoarthritis ipsilateral to the target knee

- Ongoing infection disease including but not limited to HIV, Hepatitis B or C.

- 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

- At risk for post procedure bleeding or infection

- Is taking anti-platelets or anti-coagulants (low-dose aspirin permitted)

- Has had an active malignancy with the last 5 years

- Previous cartilage repair procedures

- Major injury to the target knee within 12 months of screening

- Active ulcer or infection on the skin of the target knee within 1 month of screening

- Surgery on the target knee within 6 months of screening

- Valgus or varus of the target knee >10 degrees

- Has total knee arthroplasty or other knee surgery planned within the next 12 months.

- Participation in another investigation study within 3 months

- Unable to complete requisite follow-up and 3T MRI exams

- Has cognitive impairment or cannot otherwise provide informed consent or answer
questionnaires.