Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee

Protocol TGC09201 is a multi-center, double-blind, placebo-controlled, randomized study. A
total of one hundred (100) adults with grade 3 chronic degenerative joint disease (DJD) of
the knee joint (as determined by radiographic examination) will be enrolled into the study.
TissueGene-C will be administered intra-articularly once via x-ray guidance. TissueGene-C
will be administered at a dose of 3 x 10e7 cells. Patients receiving control treatment will
receive a single normal saline injection.

The objectives of this study are to:

1. Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of
knee osteoarthritis including pain.

2. Evaluate the safety of administration of a single intra-articular dose of TissueGene-C
as evidenced by observation of the injection site for irritation or other
abnormalities, the incidence and severity of adverse events, and the changes in
physical examination findings and laboratory tests, including immune analyses.

3. Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.

4. Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance
imaging (MRI).

5. Evaluate distribution of hChonJb#7 cells out of the injection site.

6. Evaluate the efficacy of TissueGene-C by evaluating the need for total knee
arthroplasty after treatment

Inclusion Criteria:

1. Male or Female subject

2. Age 18 to 70 years

3. In general good health as evidenced by physical examination, normal hematology, serum
chemistry, and urinalysis screening laboratory results, and a negative history of
significant organ system disorders. All laboratory values must be within 20% of
normal ranges.

1. Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the
same for both men and women.

2. Blood Pressure measurements - Systolic Blood Pressure should be between
90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,

4. Patients with Grade 3 chronic osteoarthritis of the knee as determined by the
Radiographic Criteria of Kellgren and Lawrence.

5. Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤
90 on the 100-mm scale.

6. Patients should be cleared to use protocol specified equipment: 3T MRI.

7. Patients providing written informed consent after the nature of the study is fully
explained and understood by the patient.

Exclusion Criteria:

1. Age 71 or older

2. Patients with abnormal hematology, serum chemistry, or urinalysis screening
laboratory results.

3. Patients taking non-steroidal anti-inflammatory medications within 14 days of
baseline visit unless washed out as per section 3.6.4 above.

4. Patients taking steroidal anti-inflammatory medications within 2 months of baseline
visit.

5. Patients with a recent (within 1 year) history of drug abuse and/or a positive urine
drug test at the time of screening.

6. Patients receiving injections to the treated knee within 2 months prior to study
entry

7. Patients who are contraindicated for 3T MRI.

8. Patients who are pregnant or currently breast-feeding children.

9. Patients with systemic, rheumatic or inflammatory disease of the knee or
chondrocalcinosis, hemochromatosis, inflammatory arthritis, necrosis of the femoral
condyle, arthropathy of the knee associated with juxta-articular Paget's disease of
the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis,
Charcot's knee joint, villonodular synovitis, synovial chondromatosis, and/or history
of inflammatory arthropathy.

10. Patients with ongoing infectious disease, including HIV and hepatitis B or C.

11. Patients with clinically significant cardiovascular, renal, hepatic, endocrine
disease, cancer, or Type I diabetes.

12. Patients participating in a study of an experimental drug or medical device within 30
days of study entry.

13. Patients that will be unable to comply with the requisite study follow-up and are not
able to complete all of the follow-up office visits and 3T MRI exams.