Follow-up Safety and Efficacy Evaluation on Subjects Who Completed Phase I Clinical Trial

Study Overview
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Brief Summary
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This is a follow-up study to investigate the long-term safety and explore efficacy of SMUP-IA-01, for the treatment of Knee Osteoarthritis. Subjects who participated in and completed the initial stage of the Phase I trial (NCT04037345 ) will be followed-up until 60 months.

Detailed Description
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The subjects will be followed up at 6-month, 12-month, 24-month, 36-month, 48-month and 60-month after the initial administration of SMUP-IA-01.

Official Title
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Long-term Follow-up Study of Safety and Explore Efficacy in Subjects Who Completed SMUP-IA-01 Phase Ⅰ Clinical Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: SMUP-IA-01(low-dose)
* Biological: SMUP-IA-01(mid-dose)
* Biological: SMUP-IA-01(high-dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who completed the safety and explore efficacy evaluations in SMUP-IA-01 Phase I clinical trial. Subjects who have been treated with either SMUP-IA-01 at least 6 months ago. Subjects who voluntarily decided to participate and signed the consent form after receiving explanations on the clinical trial. Exclusion Criteria: Subjects who were not enrolled in phase 1 clinical trial of SMUP-IA-01 for assessing safety and explore efficacy. Other subjects, excluding those listed above, who were deemed unsuitable by the PI

Ages Eligible for Study
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Minimum Age: 19 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SMUP-IA-01(low-dose)<br>A single knee administration of SMUP-IA-01 (low-dose, 4.0 x 10^6 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) | Biological: SMUP-IA-01(low-dose)<br>* A single knee administration of SMUP-IA-01(low-dose, 4.0 x 10^6 cells/2mL)<br>* Other names: Human umbilical cord blood-derived mesenchymal stem cells;|
| Experimental: SMUP-IA-01(mid-dose)<br>A single knee administration of SMUP-IA-01 (mid-dose, 1.0 x 10^7 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) | Biological: SMUP-IA-01(mid-dose)<br>* A single knee administration of SMUP-IA-01(mid-dose, 1.0 x 10^7 cells/2mL)<br>* Other names: Human umbilical cord blood-derived mesenchymal stem cells;|
| Experimental: SMUP-IA-01(high-dose)<br>A single knee administration of SMUP-IA-01 (high-dose, 2.0 x 10^7 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) | Biological: SMUP-IA-01(high-dose)<br>* A single knee administration of SMUP-IA-01(high-dose, 2.0 x 10^7 cells/2mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of total score in WOMAC (Western Ontario and McMaster University) | Comparing WOMAC total score changes with baseline scores of SMUP-IA-01 phase I trial and scores of f/u study at 12 months, 24 months, 36 months, 48 months and 60months after treatment (score range 0-96, higher score represent worse symptoms). | Month 12, 24, 36, 48 and 60 after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of score in WOMAC three subscales (Pain, stiffness, physical function) | The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). | Month 12, 24, 36, 48 and 60 after treatment | 
| Change of score in 100 mm VAS (Visual Analogue Scale) | The score ranges from 0 or no pain to 100 very severe pain | Month 12, 24, 36, 48 and 60 after treatment | 
| Change of score in IKDC(International Knee Documentation Committee) | The scores for each category are summed up and divided into 87, which is the maximum score possible, and then is evaluated by converting it into a scale of 100 points. Higher score indicates better function and less symptoms for the knee. | Month 12, 24, 36, 48 and 60 after treatment | 
| Change of score in WORMS(Whole-Organ Magnetic Resonance iMaging Score) | For structural and tissue evaluation of knee, MRI image of detailed knee parts are graded from min. 0 to max. 6. Lower number indicate normal status | Month 12 and 24 after treatment | 
| Change in K&L(Kellgren-Lawrence) grade | The K & L grade is 0 to 4 Grade, which means that the higher the grade, the greater the joint damage and the stenosis of the joint | Month 12 and 24 after treatment | 
| Change in joint space width | Evaluation of disease progression in target knee as ascertained by change from baseline in joint space width (JSW) determined using radiography | Month 12 and 24 after treatment | 
| Change in mechanical axis, anatomical axis | The degree of deformation of the lower half of the body is measured by measuring the angles of the mechanical axis and the anatomical axis with respect to the vertical axis. Mechanical axis: A line connecting the femoral head center point and the ankle joint center point. Anatomical axis: The middiaphyseal line of the femur and tibia | Month 12 and 24 after treatment | 
| Rate of surgery to treat application site after treatment of SMUP-IA-01 | Rate of surgery to treat application site after treatment of SMUP-IA-01 | Month 6, 12, 24, 36, 48 and 60 after treatment | 
| Changes in biomarker | Comparing biomarker changes with baseline of SMUP-IA-01 phase I trial and scores of f/u study at 12 months after treatment. urine C-terminal cross-linking telopeptides of collagen type II (CTX II), serum cartilage oligomeric matrix protein (COMP), serum matrix metalloproteinase-3 (MMP-3) | Month 12 after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human umbilical cord blood derived mesenchymal stem cells, Knee Osteoarthritis