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

A Phase II Study to Determine the Efficacy and Safety of Allogeneic Human Chondrocytes Expressing TGF-β1 (TissueGene-C) in Patients With Grade 3 Chronic Degenerative Joint Disease of the Knee

The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.

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.