Safety and Biological Efficacy Study of TisssueGene-C to Degenerative Arthritis

Study Overview
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Brief Summary
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The primary purpose of the this study is to evaluate the safety of TissueGene-C, a gene therapy product that uses allogenic human chondrocytes expressing Transforming Growth Factor(TGF)-β1 by assessing the inflammation at the injection site, the incidence and severity of the adverse events, the physical examination findings, and the laboratory test results after the intra-articular injection of TissueGene-C. And Secondary purpose is to evaluate the biological efficacy (knee pain, range of motion, functional tests, and MRI) of TissueGene-C and the distribution of TissueGene-C outside the injection site.

Detailed Description
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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 clinical trial Phase 1, we compare three different dose levels of TisssueGene-C in 6 months with 12 outpatients with degenerative arthritis. The patients are randomized by three different dose levels of TisssueGene-C in 1:1:1 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 Dose-escalating, Single-center, Phase I Clinical Trial to Investigate the Safety and Biological Efficacy of TissueGene-C 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(Medium dose)
* Biological: TissueGene-C(High dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients Patients aged 45 years or more with Grade IV [based on the International Cartilage Repair Society(ICRS) evaluation criteria from the MRI scan results] degenerative arthritis of the knee, whose symptoms had not been relieved by the conventional symptomatic treatment Healthy, with no major physical examination, hematology, serum chemistry, and urine test findings and no significant medical history Patients with cartilage damage sized 2-6 cm2 (based on the ICRS evaluation criteria from the MRI scan results) Voluntarily agreed to participate in this study and signed the informed consent form Exclusion Criteria: Showed clinically significant hematology, serum chemistry, or urine test results at the screening visit Took an anti-inflammatory medication (prescribed or over-the-counter), including natural medicine, within 14 days from the administration of the investigational product Has a history of drug abuse within one year from the enrollment, or the urine test or blood alcohol test result was positive at the screening visit Received any injection in the target knee within two months before the initiation of the 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 the tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's disease in the knee joint, villonodular synovitis, and synovial chondromas) With an infectious disease, including HIV or hepatitis (HBV/HCV) With a history 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 Showed positive drug test results at the screening visit Did not agree to use a contraceptive method (male and female)

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 doses of 3.0 x 10^6 cells | Biological: TissueGene-C(Low dose)<br>* 3.0 x 10^6 cells<br>|
| Experimental: TissueGene-C(Medium dose)<br>Single intra-articular injection to the damaged knee joint at doses of 1.0 x 10^7 cells | Biological: TissueGene-C(Medium dose)<br>* 1.0 x 10^7 cells<br>|
| Experimental: TissueGene-C(High dose)<br>Single intra-articular injection to the damaged knee joint at doses of 3.0 x 10^7 cells | Biological: TissueGene-C(High dose)<br>* 3.0 x 10^7 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events after the administration of TissueGene-C | Number of Participants with Adverse Events after the administration of TissueGene-C | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in MRI scan | Change in the MRI scan results after the administration of TissueGene-C | before and 28 days, 3 months, and 6 months | 
| Change in the Knee Society Clinical Rating System(KSCRS) test results | Comparative Evaluation of knee exam | before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months | 
| Changes in WOMAC scores | Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities(WOMAC) | before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months | 
| Changes in 100 mm-VAS | Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS) | before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months | 
| Analysis of the TGF-β1 expression using Enzyme-linked Immunosorbent Assay(ELISA) and Polymerase Chain Reaction(PCR) | Analysis of the TGF-β1 expression using Enzyme-linked Immunosorbent Assay(ELISA) and Polymerase Chain Reaction(PCR) | before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months | 
| Replication-competent retrovirus test (RCR test) | Replication-competent retrovirus test (RCR test) | before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months | 

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