Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis

TissueGene-C is a biological new drug which consists of normal chondrocyte cells and transduced chondrocyte cells that express growth factor to modify osteoarthritis symptom for long term period.

During the Phase 3 clinical trial , we will compare TissueGene-C to placebo in 26, 52 weeks trial with 156 outpatients who have osteoarthritis. The outpatients are randomized to TissueGene-C or placebo in 1:1 ratio, and they will be monitored and recorded in terms of alleviating symptoms, sports activities, function of the knee, and the presence of adverse events.

Inclusion criteria

• Male or female patients at least 19 years of age
• Patients diagnosed with degenerative arthritis
• Patients with IKDC(Knee Documentation Committee subjective score) score of 60 or below
• Patients with 100 mm VAS(Visual Analog Scale) score of 40 or above
• With Grade 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence
• With an International Cartilage Repair Society(ICRS) Grade III or IV cartilage damage in the major lesions, as confirmed through an MRI scan
• With a Body Mass Index(BMI) of higher than18.5 and lower than 30
• Patients who satisfies the clinical/radiational criteria by the American College of Rheumatology (ACR) guidelines, and applies to one of the following.

• Older than 50
• Morning stiffness for less than 30 minutes
• Crepitus and Osteophytes
• With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms
• With no alleviation of the symptoms even after at least three months of non-surgical treatment
• Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history
• Agreed to use an effective contraceptive method during the study period
• Voluntarily agreed to participate in this study, and signed the informed consent form

Exclusion criteria

• Showed clinically significant hematology, serum chemistry, and urine test results at the screening visit
• Regarding inclusion criteria 6. following patients should not be included

• patients with a major lesion of ICRS grade 4 which is larger than 6cm2(for patient with ICRS grade 4)
• patients with a major lesion of ICRS grade 3 which is larger than 6cm2(for patient without a ICRS grade 4),
• Patient who had skin disease around target knee
• patients who have a positive skin reaction to CS-10
• Patients who had been administered with drugs such as oriental medicine, glucosamine and chondroitin within 14 days of baseline visit
• Patients taking steroidal anti-inflammatory medications within 14 days of baseline visit
• Patients with severe pain in other areas that could effect the diagnosis of the symptoms of the
• History of surgery like arthroendoscopy within the past 6 months on the target knee
• Patients who had been administered with immunosuppressants, including antirheumatic drugs (including methotrexate or antimetabolite), within the past 3 months
• Patients who had been treated with physical therapy or herbal remedy (acupuncture, heat etc.) within 2 weeks of baseline visit
• History of injection within the past 3 months on the target knee
• Pregnant or breastfeeding female
• With another joint disease apart from degenerative arthritis (e.g., systemic rheumatic inflammatory disease associated with the knee or chondrocalcinosis, hemachromatosis, inflammatory arthritis, necrosis of the trochanter, Paget's disease adjacent to a joint in the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's disease in the knee joint, villonodular synovitis, synovial chondromas)
• With an infectious disease, including HIV or hepatitis
• With any of the following clinically significant diseases:

• heart disease (e.g., myocardial infarction, arrhythmia, other serious heart diseases, coronary artery bypass graft)
• kidney disease (e.g., chronic renal failure, glomerulonephritis)
• liver disease (e.g., liver cirrhosis, fatty liver, acute or chronic liver disease)
• endocrine disease (e.g., hyperthyroidism, hypothyroidism, thyroiditis, diabetes insipidus, Cushing's disease)
• insulin-dependent diabetes mellitus
• medical history of past or current malignant tumor
• In particular, the tumors that TissueGene-C may aggravate can be screened using the following tests:

• Leukemia (White Blood Cell level in the hematology)
• Osteochondroma, Chondromas, Chondroblastoma, Chondromyxoid fibroma, Chondrosarcoma (Alkaline phosphatase level in the hematology)
• Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study
• Patients who administered the TissueGene-C from past clinical trial
• Considered inappropriate by the investigator for participation in this study