Clinical Trial to Evaluate Efficacy and Safety of JOINTSTEM in Patients With Degenerative Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of autologous transplantation of Adipose Tissue derived Mesenchymal stem cells (MSCs) in patient with Knee Osteoarthritis.

Detailed Description
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JOINTSTEM is an OA treatment that uses autologous adipose-derived mesenchymal stem cells. As it does not use allogenic tissues and is incubated without additional genetic modification or mechanical and chemical modification through differentiation, it is classified as 'autologous cell therapy' and is completely free of immunologic rejection. It primarily aims to improve pain and joint function, and secondary, to regenerate cartilage. The intra-articular injection of JOINTSTEM is expected to stimulate the regeneration and growth of cartilage, and to innovatively improve pain and joint function with cartilage regeneration within six months. The subjects of this therapy were regenerative patients with K&L grade 2 4 aged 18 or older. JOINTSTEM is expected to be used in patients who have significantly damage cartilage due to its cartilage regeneration ability, in addition to its improvement of pain and joint performance. A;sp. Patients who had already undergone knee arthroplasty can delay their additional surgery with the use of JOINTSTEM. For dose who still have their own cartilage, arthroplasty is not an immediate treatment option, and osteoporosis patients who cannot undergo arthroplasty due to their advanced age can receive JOINTSTEM.

Official Title
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Multicenter, Randomized, Double-Blind, Placebo Controlled Phase Ⅱb Clinical Trial to Evaluate Efficacy and Safety of JOINTSTEM in Patients With Degenerative Arthritis

Conditions
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Degenerative Arthritis, Knee Osteoarthritis

Intervention / Treatment
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* Biological: JOINTSTEM
* Drug: Saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 and older, male and female Patients must consent in writing to participate in the study by signing and dating an informed consent document Diagnosis of osteoarthritis by ACR osteoarthritis of the knee Diagnosis of osteoarthritis by radiographic criteria of Kellgren and Lawrence grade 2-4 More than Grade 4 (0 10 point numeric scale) pain at least for 12 weeks Diagnosis of osteoarthritis of class Ⅰ Ⅲ by ACR(American College of Rheumatology Criteria) Global functional criteria Patient who agree with contraception Exclusion Criteria: Preparing for Pregnancy or Pregnant women or lactating mothers. Patients with Body Mass Index (BMI) > 35. Patients with other disease including : Septic arthritis, Rheumatoid or Inflammatory joint disease, Crystalline disease (gout or pseudogout), Paget disease, Articular fractures, Ochronosis, Acromegaly, Hemochromatosis, Wilson's disease, Osteochondromatosis, Hereditary disorder Patients with serious condition internal medicine disease Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C (HCV), syphilis at screening indicative of current of pass infection. Patient with behavioral disorders, cognitive disorders and chronic mental symptoms Patient with significant neurologic or psychiatric disorders Patients who alcohol, drug abuse history Patients who had participated in other clinical trials within 12 weeks prior to this study. Patients who received any drug by intra-articular injection for treatment within 2 months prior to this enrollment. Patients who experienced as the knee joint cartilage and stem cell therapy Patients who the principal investigator considers inappropriate for the clinical trial due to any other reasons than those listed above Patients who penicillin hypersensitivity reactions -

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Jointstem<br>Autologous Adipose Tissue derived MSCs | Biological: JOINTSTEM<br>* Jointstem (Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml), 1 time injection<br>* Other names: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml;|
| Placebo Comparator: Saline solution<br>Sodium chloride | Drug: Saline solution<br>* Saline solution (Sodium chloride 9mg/ml), 1 time injection<br>* Other names: Sodium chloride 9mg/ml;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC score | Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC 3 subscale | Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC) | 24 weeks | 
| KOOS (Knee Injury & Osteoarthritis Outcome Score) | Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS) | 24 weeks | 
| SF(Short Form)-36 Score | The SF(Short Form)-36 Health Survey is a 36-item, patient-reported survey of patient health. | 24 weeks | 
| Global assessment of disease activity | Change From Baseline in Patient's & Physician's Global Assessment of Disease Activity Score at 12,24 weeks by 100mm VAS(Visual Analogue Scale) | 24 weeks | 
| Overall satisfaction | Patient's overall satisfaction on a 0-100mm VAS(Visual Analogue Scale) | 24 weeks | 
| X-ray | X-ray perform to measure with Kellgren-Lawrence grade | 24 weeks | 
| MRI scan | MRI perform to measure cartilage defect size change from baseline up to 24weeks | 24 weeks | 
| Arthroscopy evaluation | Arthroscopy performs to evaluate any change in cartilage defect at the time of cell injection, and at 24 weeks after injection | 24 weeks | 
| Histological evaluation | Biopsy specimens subject to safranin-O staining and immunohistochemistry for type I and II collagen. Thickness of the articular cartilage before and after injection measure, and specimens evaluate with ICRS(International Cartilage Repair Society) II by a blind histopathologist. | 24 weeks | 
| VAS | Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS) | 24 weeks | 
| IKDC | Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC) | 24 weeks | 
| ROM | change from baseline in knee flexion Range of Motion(ROM) at 12,24 weeks by physical examination | 24 weeks | 
| Quadriceps power | Change from baseline in quadriceps power at 12,24 weeks by physical examination | 24 weeks | 
| effusion | Change from baseline in 4-grade knee effusion at 12,24 weeks | 24 weeks | 
| Crepitus | Change from baseline in asymptomatic and symptomatic crepitus at 12,24 weeks by physical examination | 24 weeks | 
| Ligament laxity | Change from baseline in ligament laxity at 12,24 weeks by physical examination | 24 weeks | 
| Medial joint line tenderness | Change from baseline in 4-grade(none, mild, moderate, severe) medial joint line tenderness at 12,24 weeks by physical examination | 24 weeks | 
| Pes tenderness | Change from baseline in 4-grade(none, mild, moderate, severe) Pes tenderness at 12,24 weeks by physical examination | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell, adipose tissue derived mesenchymal stem cell, osteoarthritis, degenerative arthritis, biostar, Rbio