Efficacy and Safety Study of TissueGene-C Mixed With Fibrin-glue for the Patients With Degenerative Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether TissueGene-C, allogeneic human chondrocytes expressing Transforming Growth Factor(TGF)-b1, mixed with fibrin-glue is effective and safe in patients with degenerative arthritis.

Detailed Description
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TissueGene-C is a biological new drug which consists of non-transduced chondrocytes and transduced chondrocytes that express TGF-b1 to regenerate the damaged cartilage. During the clinical trial Phase 2, the investigators compare low dose or high dose TissueGene-C in 12 - months trial with 18 outpatients who have degenerative arthritis. The patients are randomized to two dose levels of TissueGene-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 Single-blind, Randomized, Parallel-group, Multi-center Phase 2 Study to Determine the Efficacy and Safety of TissueGene-C Mixed With Fibrin-glue in Patients With Degenerative Arthritis

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: Female or male aged 18 years or more Diagnosed with degenerative arthritis of the knee With an IKDC score of 60 or lower at the screening visit With a BMI of higher than18.5 and lower than 30 With an International Cartilage Repair Society(ICRS) Grade IV cartilage damage in the major lesions, as confirmed through an MRI scan With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms With major lesions defect size 2 cm2   10cm2 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 Mechanical axis (HKA) is greater than 5° Patients receiving injections to the treated knee within 2 months prior to study entry Patients who are pregnant or currently breast-feeding children With another joint disease (e.g., inflammatory arthritis, infectious arthritis) 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, 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 Considered inappropriate by the investigator for participation in this study

Ages Eligible for Study
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Minimum Age: 18 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>TissueGene-C (1.0 x 10^6 cells per cm^2 of the cartilage defect) combined with fibrin-glue | Biological: TissueGene-C (Low dose)<br>* TissueGene-C at 1.0 x 10^6 cells mixed with fibrin-glue<br>|
| Experimental: Experimental: TissueGene-C (High dose)<br>TissueGene-C (3.0 x 10^6 cells per cm^2 of the cartilage defect) combined with fibrin-glue | Biological: TissueGene-C (High dose)<br>* TissueGene-C at 3.0 x 10^6 cells mixed with fibrin-glue<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 and 48 | 

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, 24 and 48 | 
| Changes in KOOS scores | Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 0, 24 and 48 | 
| Changes in 100 mm-VAS | Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS) | Week 0, 24 and 48 | 
| Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) | Comparison of pre-procedure MRI scans to those obtained at pre-dosing and at months 6 and 12 by an independent radiographic reviewer | Week 0, 24 and 48 | 
| Changes in ICRS Cartilage Repair Assessment |  | week 0 and 48 | 
| 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 and 24 | 
| Changes in KOOS QOL Sub-scale scores |  | Week 0, 24 and 48 | 
| Proportion of Patients Use of Rescue Medication |  | Week 12, 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell mediated gene therapy, Osteoarthritis, Fibrin-glue, Degenerative Arthritis