A Phase 2b/3a Study to Evaluate the Efficacy and Safety of JointStem in Patients Diagnosed as Knee Osteoarthritis

Study Overview
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Brief Summary
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This study is a double-blind, randomized, placebo controlled, multi-center, superiority study to evaluate the efficacy and safety of JointStem, autologous adipose tissue derived mesenchymal stem cells (AdMSC), in patients diagnosed as knee osteoarthritis. Following a 2-week screening period, approximately 140 subjects will be randomly assigned into one of the following two arms in a 1:1 ratio (1 JointStem : 1 Placebo). After each subject completes 48-Weeks visit (Visit 8) and the data management team confirms all individual data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

Detailed Description
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Study Procedures: Visit 1 (Week -7) - Screening Visit 2 (Week -5) - Baseline and Randomization (Lipoaspiration) Visit 3 (Week 0) - Treatment (Intra-articular injection) Visit 4 (Week 4) - 4 weeks follow-up Visit 5 (Week 12) - 12 weeks follow-up Visit 6 (Week 24) - 24 weeks follow-up Visit 7 (Week 36) - 36 weeks follow-up Visit 8 (Week 48) - 48 weeks follow-up (End of Study)

Official Title
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A 48-Weeks, Phase 2b/3a, Double-Blind, Randomized, Placebo Controlled, Multi-center, Superiority Study to Evaluate the Efficacy and Safety of JointStem, Autologous Adipose Tissue Derived Mesenchymal Stem Cells in Patients Diagnosed as Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: JointStem
* Other: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who had osteoarthritis of knee diagnosed (according to the clinical and American College of Rheumatology Criteria) Subject who has ≥ 34 on WOMAC function score at Screening and Baseline Subject who has knee pain ≥ 70 mm for one knee out of 100 mm on VAS (Visual Analog Scale) at Screening and Baseline Subject who has radiographic evidence of grade 3 osteoarthritis in the study knee based on the Kellgren and Lawrence radiographic criteria. Subjects whose knee pain persists for at least 12 weeks (about 3 months) prior to screening and does not improve symptoms with non-operative treatment options 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 is willing and able to give written informed consent for participation in the study Exclusion Criteria: Subject who has Body Mass Index (BMI) > 35 kg/m2 Subject judged by the investigator to have a history of clinically significant disease Subject who has any of following clinically significant disease Autoimmune diseases Paget's disease, ochronosis, acromegaly, hemochromatosis, or Wilson's disease Genetic diseases (hyperkinesia, collagen gene abnormality, etc.) Inflammatory joint disorders (e.g. rheumatoid inflammation) Infectious joint disorders (e.g. septic arthritis) Other joint disorders (e.g. gout, recurrent pseudogout, articular fracture, primary osteochondrosis, villonodular synovitis) Subject who has any history of cancer or currently receiving treatment for a current cancer diagnosis Subject who is positive in pathogenic test (HIV, viral hepatitis, or syphilis) Subject who has heart diseases (myocardial infarction, coronary artery bypass graft surgery, arrhythmia, or other serious heart diseases) or has history of heart diseases within 6 months prior to Screening Subject who have received any intra-articular therapy in any joint within 6 months prior to Screening, or surgery on the relevant knee including articular endoscopic procedures within 6 months prior to Screening Subject who has history of prolotherapy, or platelet rich plasma injection within 6 months prior to Screening Subject who have received long-acting hyaluronic acid injection (e.g. Synvisc-One®, etc.) within 6 months prior to Screening Subject who has history of stem cell therapy Subject who have significant lab abnormalities for the following parameters (If the value is within 10% of the listed laboratory exclusion criterion value and the value is considered not to be clinically significant by the investigator, the subject can be considered for enrollment): Serum ALT and AST > 2 x upper limit of normal Serum creatinine out of normal range PT/INR out of normal range Hemoglobin < 10 g/dL for female subject and hemoglobin < 11 g/dL for male subject Platelets out of normal range Subject for whom the investigator judges the lipoaspiration can cause any problem Subject who has history of local anesthetic allergy Subject who has taken anti-inflammatory drugs (prescription and non-prescription NSAIDs), symptomatic slow acting drugs (glucosamine, chondroitin sulfate, diacerhein etc.), or oral steroids (prednisone etc.) within 14 days prior to Screening (however, those who undergo a 14-day wash-out period can participate.) Subject who is an active drug/alcohol abuser Pregnant or breast-feeding women, or women or men who are not using appropriate method of contraception (appropriate method includes hormones, bilateral tubal ligation, and barrier method with spermicide, and intra-uterine device for women and vasectomy and barrier method with spermicide for men; subjects should agree to use appropriate method) Subject who is enrolled in any other clinical trials within 3 months from Screening Subject who received the COVID-19 vaccines within 1 week from Visit 2 (Lipoaspiration, baseline) Subject who the principal investigator considers inappropriate for the study due to any other reasons than those listed above

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JointStem<br>Autologous Adipose tissue derived Mesenchymal Stem Cells(AdMSC) | Drug: JointStem<br>* Autologous Adipose tissue derived Mesenchymal Stem Cells (AdMSC)<br>|
| Placebo Comparator: Placebo<br>Normal Saline with Autologous Serum | Other: Placebo Control<br>* Normal Saline with autologous Serum<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) function Score | Change from baseline in WOMAC function score at Week 48 | Baseline and Week 48 | 
| Visual Analog Scale (VAS) score | Change from baseline on Visual Analog Scale (VAS) score at Week 48 | Baseline and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscale (Function) | Change from baseline in WOMAC subscale (Function) score at Week 12, 24, and 36 | Week 12, 24 and 36 | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscale (Pain) | Change from baseline in WOMAC subscale (Pain) score at Week 12, 24, 36, and 48 | Week 12, 24, 36, and 48 | 
| Total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score | Change from baseline in total WOMAC score at Week 12, 24, 36, and 48 | Week 12, 24, 36, and 48 | 
| Visual Analog Scale (VAS) score | Change from baseline in VAS score at Week 12, 24 and 36 | Week 12, 24 and 36 | 
| International Knee Documentation Committee (IKDC) score | Change from baseline in IKDC score at Week 12, 24, 36, and 48 | Week 12, 24, 36, and 48 | 
| 36-Item Short Form health survey questionnaires (SF-36) score | Change from baseline in SF-36 score at Week 12, 24, 36, and 48 | Week12, 24, 36, and 48 | 
| Kellgren-Lawrence grade | Change from baseline in Kellgren-Lawrence grade of knee osteoarthritis determined by X-ray at Week 48 | Week 48 | 
| Number and amount of rescue medication use | The number and amount of rescue medication use at Week 12, 24, 36, and 48 | Week 12, 24, 36, and 48 |