Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis

Study Overview
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Brief Summary
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To assess the efficacy and safety of the intra-articular injection of TissueGene-C in patients with degenerative arthritis of the knee

Detailed Description
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TissueGene-C is a biological new drug which consists of non-transduced chondrocytes and transduced chondrocytes that express Transforming Growth Factor(TGF)-b1 to regenerate the damaged cartilage. During the clinical trial Phase 2A, we compare low dose or high dose TissueGene-C in 6 months trial with 28 outpatients who have degenerative arthritis. The patients are randomized to two dose levels of TisssueGene-C by 1:1 ratio, and they are monitored and recorded for alleviating symptoms, sports activities, function of the knee, and the presence of adverse events.

Official Title
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A Multicenter, Single-blind, Phase 2A Clinical Trial to Evaluate the Efficacy and Safety of TissueGene-C, a Cell-mediated Gene Therapy, in Degenerative Arthritis Patients

Conditions
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Degenerative Arthritis

Intervention / Treatment
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* Biological: TissueGene-C(Low dose)
* Biological: TissueGene-C(High dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 45 years or more With grade 4 degenerative arthritis of the knee [based on the International Cartilage Repair Society(ICRS) evaluation criteria from the MRI results] With less than 6 cm2major lesions With major lesions (grade 4) concentrated in only one section of the knee and considered the main cause of the clinical symptoms Unresponsive to conventional symptomatic treatment Healthy and with no major physical examination, hematology, serum chemistry, and urine test findings 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: Abnormal screening laboratory test (hematology, serum, and urine test) findings Took anti-inflammatory medications (prescribed or over-the-counter), including natural medicines, within 14 days before the injection of the investigational product Took antirheumatic drugs (e.g., methotrexate or antimetabolites) within three months before enrollment in this study Has a history of drug abuse within one year from the enrolment, or has positive results in the urine drug test or serum alcohol test at the screening visit Received an injection in the target knee within two months before enrollment in this study 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, and synovial chondromas) With a current infectious disease, including HIV or hepatitis Has any of the following clinically significant diseases: heart disease [e.g., myocardial infarction, arrhythmia, other serious heart disease, coronary artery bypass graft (CABG)] 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 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 Considered by the investigator inappropriate for participation in this study

Ages Eligible for Study
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Minimum Age: 45 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TissueGene-C (Low dose)<br>Single intra-articular injection to the damaged knee joint at a dose of 6.0 x 10^6 cells | Biological: TissueGene-C(Low dose)<br>* TissueGene-C at 6.0x10^6 cells<br>|
| Experimental: TissueGene-C (High dose)<br>Single intra-articular injection to the damaged knee joint at a dose of 1.8 x 10^7 cells | Biological: TissueGene-C(High dose)<br>* TissueGene-C at 1.8x10^7 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in IKDC Subjective Knee Evaluation | Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC) | Week 0, 12 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in WOMAC scores | Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities(WOMAC) | Week 0, 12 and 24 | 
| Changes in 100 mm-VAS | Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS) | Week 0, 12 and 24 | 
| Comparative Evaluation of Knee MRI | Change in the Magnetic Resonance Images (MRI) scan results after the administration of TissueGene-C | Week 0, 12 and 24 | 
| Number of Participants with Adverse Events | Allergic reaction, Injection site reaction , Infection in the injection site, Fibrosis, Fibrosis-deep connective tissue, Muscular/skeletal hypoplasia, TGF-β1 Enzyme-linked Immunosorbent Assay (ELISA) result, Polymerase Chain Reaction(PCR) for the vector DNA test results | Week 0, 2, 4, 12 and 24 | 
| Evaluation of Physical examination and laboratory tests | Vital signs, Physical examination findings, Monitoring of the hematology, serum chemistry, and urine test results | Week 0, 2, 4, 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chondrocyte cells, Osteoarthritis, gene therapy