Clinical Study of Intra Articular Injection of Catholic MASTER Cell (Bone Marrow Derived Mesenchymal Stem Cell) in Knee Osteoarthritis

Study Overview
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Brief Summary
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objective - safety and efficacy evalaution of MASTER cells injected into knee of patients with osteoarthritis background osteoarthritis Osteoarthritis is severe and intractable musculoskeletal disease that eventually leads to joint failure and pain due to inflammation and joint injury. OA is one of the most prevalent diseases. The prevalence increases with age, but overuse and trauma can result in OA in young population as well. Injured cartilage can not be regenerated spontaneously, untreated injured cartilage eventually leads to osteoarthritis. Surgical treatment may repair the damage but the reparied cartilage may turn out to be fibrocartilage rather than hyaline cartilage. Curent treatment medical therapy: medication for symptom relief, together with exercise. Medications include NSAIDS visco-supplement. surgical therapy: total knee replacement arthroplasty to overcome such limitations, cell therapy such as stem cell/ chondrocyte injection is being investigated Hypothesis - Intra articular injection of MASTER cells will show safety and efficacy in terms of pain and functional improvement. Protocol 1) deisgn : Injection of MASTER cell 1X 10^8 cells/2cc (experimental arm) or 2cc saline (placebo arm) into knee of patients with osteoarthritis 2) outcomes primary outcome : safety evaluation(adverse event) secondary outcomes : check on 1,2,3,6,9,12 months, atient reported outcome (WOMAC, KOOS, IKDC, pain VAS) 3,12 months SF-36, knee MRI score, serum cytokine, bone turnover marker 12 months x-ray 3) Disease osteoarthritis 4) Subjects inclusion : age 20-80yrs, diagnosed with OA according to ACR criteria for knee OA, baseline pain VAS equal or more than 50mm exclusion: lower extremities surgery within 6months or planned surgery, concommitant systemic rheumatic diseases that can affect the results of the trial, steroid intraarticular inejction into the index knee within 3months, clinicallly meaningful abnormal lab tests (liver function, kidney function) 5) evaluation primary outome : compare the number and proportion of of adverse event and lab test abnormalities between the two arms secondary outome change of 100mm pain VAS change of Western Ontario and McMAster Universities Osteoarthritis (WOMAC) pain VAS, IKDC, KOOS total score change WOMAC sub scale, IKDC, KOOS chagne of KHAQ change of MRI indices change of x-ray( joins space narrowing) change of serum ESR/CRP, CTX-II

Official Title
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Randomized Double-blind Clinical Study of Intra Articular Injection of Catholic MASTER Cell in Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: Catholic MASTER cell
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-80 diagnosed with knee osteoarthritis (OA) according to ACR classfication criteia for knee OA symptomatic OA that lastede for at least 3 months before screening Baseline Pain VAS ≥50 mm treated with medication such as acetaminophen, tramadol, NSAID for at least 1month due to OA pain X-ray Kellgren-Lawrence grade 1 4 volauntarily enrolled with informed consent no improvement with medical treatment for at least 3 months Exclusion Criteria: disease in spine or lower extremities that can affect the outcome of index knee surgery on lower extremities within 6month before injection or planned joint symptoms that can affect the interpretation of the trial data or prevent the subject from enrollement including but not limited to symptomatic fracture, fibromyalgia, rheumatoid arthritis, reactive arthritis steroid injection to the index knee within preivious 3months hyaluronic acid injection to the index knee within preivious 6months underwent cell therapy or gene therapy in the past more than 3 times upper normal limit in one or more of the followings: serum creatinine, bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or more than 3 times upper normal limit in two or more of the followings: bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) participation in a different clinical trial other than this within 4 weeks after initiation of the current study use (reccuent use or addiction) of substances that can affect pain sensation such as narcotics females of childbearing age who do not consent to effective contraceptive methods during the study period pregnant or lactating woman malignancy considered to be inappropriate for the trial by investigators

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MASTER cell<br>Intraarticular injection of Catholic MASTER cell, 1 time, 1 x 10^8 cells/DMEM 5cc, into knee joint of patients with osteoarthritis | Biological: Catholic MASTER cell<br>* Injection of CATHOLIC MASTER cells 1 x 10^8 cells/DMEM 5cc into knee of patents with osteoarthritis<br>|
| Placebo Comparator: Saline<br>Intraarticular injection of saline, 1 time, 5cc, into knee joint of patients with osteoarthritis | Other: Saline<br>* Injection of saline 5cc into knee of patents with osteoarthritis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event according to CTCAE 5.0, clinically meaningful abnormalites in laboratory tests (blood) |  | Change from Baseline blood abnormalities at 12 month | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) score |  | Change from Baseline WOMAC score at 12 month | 
| Knee injury and Osteoarthritis Outcome Score (KOOS) |  | Change from Baseline KOOS score at 12 month | 
| International knee documentation committee (IKDC) |  | Change from Baseline IKDC score at 12 month | 
| Cartilage damage evaluation through knee MRI |  | Change from Baseline cartilage morphology at 12 month | 
| SF-36 questionnaire |  | Change from Baseline SF-36 score at 12 month | 
| Serum inflammatory cytokine, acute phase reactant, bone turnover marker |  | Change from Baseline cytokine level, acute phase reactant, bone turnover marker level at 12 month | 
| Cartilage damage evaluation through knee x-ray |  | Change from Baseline cartilage and bone morphology at 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, mesenchymal stem cell