A Phase 2 Study to Evaluate the Efficacy and Safety of JointStem in Treatment of Osteoarthritis

Study Overview
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Brief Summary
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This study is a double-blind, randomized, controlled study with two arms to evaluate JointStem as a treatment for subjects with osteoarthritis. Following a 2-week screening period, approximately 30 subjects will be randomly assigned into one of the following two arms in a 2:1 ratio (2 JointStem : 1 positive control). After each subject completes 6-month visit (Visit 6) and the data management team confirms all data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.Only subjects who are assigned will be requested to visit the study center for 9-month and 12-month follow-up visits (Visits 7 and 8). To see long-term effects of JointStem, all subjects who complete Visit 6 will be requested to visit the study center at 24-month after the injection.

Official Title
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A Phase 2, Double-Blind, Randomized, Controlled Study to Evaluate the Efficacy and Safety of JointStem, Autologous Adipose Tissue Derived Mesenchymal Stem Cells, in Treatment of Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: JointStem
* Drug: Synvisc-One


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who can give written informed consent Male or female of any race, aged 22-60 Subject who had osteoarthritis of knee diagnosed at least six months prior to Screening Subject who has joint pain ≥ 40mm on VAS (Visual Analog Scale) at Screening Subject who has swelling, tenderness and active range of motion ≥ Grade I at Screening Subject who seeks invasive interventions of intra-articular injections Subject who is willing to discontinue all pain medications for osteoarthritis except rescue medication (< acetaminophen 3.25 g per day) at least 72 hours prior to screening and throughout the duration of study Subject who has radiographic evidence of grade 3 to 4 osteoarthritis based on the Kellgren and Lawrence radiographic criteria. Female subject who is neither pregnant nor lactating Subject who is able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: Subject who has Body Mass Index (BMI) > 35 kg/m2 Subject who has unstable knees Subject who took any NSAID within two weeks from Screening Subject who had any intra-articular injection therapy in any joint within 2 months from Screening Subject who has any clinically significant disease, which is judged by the investigator to affect this clinical trial Subject who has inflammatory arthropathy (rheumatoid, psoriatic, or avascular necrosis), and post traumatic or septic arthritis Subject who has chondrocalcinosis, Paget's disease, Villonodular synovitis, and other non-OA joint diseases Subject who has HIV/viral hepatitis Subject who had knee surgery or radiation therapy in the affected joint within 6 months from Screening Subject who had CVA attack within 6 months from Screening Subject for whom the investigator judges the liposuction can cause any problem Subject who has significant lab abnormalities Subject who has history of local anesthetic allergy Subject who took immunosuppressants such as Cyclosporin A or azathioprine within 6 weeks from Screening (If a subject uses aspirin or plavix) Subject for whom it is determined that it would not be safe to stop the aspirin/plavix therapy for 2 weeks prior to Visit 2 Subject who uses anticoagulants which cannot be stopped or corrected Subject who had oral or intra-muscular corticosteroids within 30 days from Visit 2 Subject who had intra-articular corticosteroid injection in any joint within 30 days from Visit 2 Subject who had intra-articular hyaluronic acid injection within 30 days from Visit 2 Subject who has known hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations or gram positive proteins Subject who has knee joint infections or skin diseases or infections in the area of the injection site Subject who has known systemic bleeding disorders Subject who is an active drug/EtOH abuser Subject who was enrolled in any other clinical trials within 2 months from Screening Subject who the principal investigator considers inappropriate for the study due to any other reasons than those listed above Subject whose MRI scan results at screening do not demonstrate any sign of cartilage damage

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 60 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JointStem<br>autologous adipose tissue derived mesenchymal stem cells (AdMSC) | Drug: JointStem<br> <br> |
| Active Comparator: Synvisc-One<br>hyaluronic acid | Drug: Synvisc-One<br> <br> * Other names: Active Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score in JointStem Group | Comparing the baseline and 6-month WOMAC scores in JointStem group Score range: 0-2,400 A score of 2,400 represents the most severe impairment and 0 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on Visual Analog Scale (VAS) in JointStem Group | Comparing the baseline and 6-month VAS scores in JointStem group Score range: 0-100 A score of 100 represents the most severe pain and 0 represents the least pain. | Baseline and 6 months | 
| MRI Improvement Evaluation in JointStem Group | Comparing the baseline and 6-month MRI improvement values in JointStem group MRI Improvement Evaluation was conducted by an MRI analysis company called 'Qmetrics'. The main radiological features evaluated were bone marrow edema, osteophytes, and cartilage. Certain features, such as the appearance of a new cartilage defect or increase in the size of existing cartilage defects or osteophytes, is generally considered an indication of osteoarthritic progression. Similarly, the diminishing in severity or size of existing abnormalities would generally be considered to be a healing(improving) response. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on WOMAC Between JointStem and Positive Control Groups | Comparing the changes of WOMAC scores between JointStem and positive control groups at 6 months Score range: 0-2,400 A score of 2,400 represents the most severe impairment and 0 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on VAS Between JointStem and Positive Control Groups | Comparing the changes of VAS scores between JointStem and positive control groups at 6 months Score range: 0-100 A score of 100 represents the most severe pain and 0 represents the least pain. | Baseline and 6 months | 
| Change From Baseline on Knee Injury & Osteoarthritis Outcome Score (KOOS) Between JointStem and Positive Control Groups | Comparing the changes of KOOS values between JointStem and positive control groups at 6 months KOOS score = 100 - [{(average score of each item) * 100} / 4 ] Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on Lysholm Knee Scoring Scale Between JointStem and Positive Control Groups | Comparing the changes of Lysholm Knee Scoring Scales between JointStem and positive control groups at 6 months Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on International Knee Documentation Committee (IKDC) Between JointStem and Positive Control Groups | Comparing the changes of IKDC scores between JointStem and positive control groups at 6 months IKDC score = {(sum of each item score) / 87} * 100 Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on RAND-36 Score Between JointStem and Positive Control Groups | Comparing the changes of RAND-36 scores between JointStem and positive control groups at 6 months Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | Baseline and 6 months | 
| Change From Baseline on WOMAC in JointStem Group | Comparing the baseline and 9-month/12-month WOMAC scores in JointStem group Score range: 0-2,400 A score of 2,400 represents the most severe impairment and 0 represents the least impairment | Baseline, 9 months and 12 months | 
| Change From Baseline on VAS in JointStem Group | Comparing the baseline and 9-month/12-month VAS scores in JointStem group Score range: 0-100 A score of 100 represents the most severe pain and 0 represents the least pain. | Baseline, 9 months and 12 months | 
| Comparison of MRI Improvement Evaluation in JointStem Group | Comparing the baseline and 9-month/12-month MRI improvement values in JointStem group MRI Improvement Evaluation was conducted by an MRI analysis company called 'Qmetrics'. The main radiological features evaluated were bone marrow edema, osteophytes, and cartilage. Certain features, such as the appearance of a new cartilage defect or increase in the size of existing cartilage defects or osteophytes, is generally considered an indication of osteoarthritic progression. Similarly, the diminishing in severity or size of existing abnormalities would generally be considered to be a healing(improving) response. | Baseline, 6 months and 12 months | 
| Change of Lysholm Knee Scoring Scale From Baseline at Months 6, 9 and 12 | Comparing the baseline and 6-month/9-month/12-month Lysholm Knee Scoring Scale in JointStem group Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | Baseline, 6 months, 9 months and 12 months | 
| Change of KOOS Score From Baseline at Month 6, 9 and 12 for JointStem Group | Comparing the baseline and 6-month/9-month/12-month KOOS scores in JointStem group KOOS score = 100 - [{(average score of each item) * 100} / 4 ] Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | baseline, 6 month, 9 month, 12 month | 
| Change of IKDC Score From Baseline at Month 6, 9 and 12 for JointStem Group | Comparing the baseline and 6-month/9-month/12-month IKDC scores in JointStem group IKDC score = {(sum of each item score) / 87} * 100 Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | baseline, 6 month, 9 month, 12 month | 
| Change of RAND-36 Score From Baseline at Month 6, 9 and 12 for JointStem Group | Comparing the baseline and 6-month/9-month/12-month RAND-36 scores in JointStem group Score range: 0-100 A score of 0 represents the most severe impairment and 100 represents the least impairment | baseline, 6 month, 9 month, 12 month |