Follow-Up Study of CARTISTEM® Versus Microfracture for the Treatment of Knee Articular Cartilage Injury or Defect

Study Overview
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Brief Summary
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This is a long term follow-up study to investigate the safety and efficacy of CARTISTEM®, human umbilical cord blood-derived mesenchymal stem cells, in repair of cartilage injury or defects, compared with microfracture. Subjects who participated in and completed the Phase III trial (NCT01041001) will be tracked until the 60 month post-treatment timepoint.

Detailed Description
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This long term follow-up study is performed to assess the long-term safety and efficacy of CARTISTEM®, human umbilical cord blood-derived mesenchymal stem cells, in repair of cartilage injury or defects, compared with microfracture. Subjects, who were either administered CARTISTEM or treated with conventional microfracture in the primary phase III study (NCT01041001), will be further observed using various subjective knee assessments and MRI T2 mapping until the 60 month post-treatment timepoint.

Official Title
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Long Term Follow-Up Study of CARTISTEM® Versus Microfracture for the Treatment of Knee

Conditions
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Degenerative Osteoarthritis, Defect of Articular Cartilage

Intervention / Treatment
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* Biological: CARTISTEM
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with knee joint cartilage defect or injury of ICRS (International Cartilage Repair Society) Grade 4 confirmed by arthroscopy (At screening, patients diagnosed as such with an MRI may be included) Male or female patients at least 18 years of age Patients whose lesion (unilateral joint) is 2 ㎠   9㎠ in size Patients with articular swelling, tenderness and active range of motion of Grade 2 or below Patients with pain in affected joint of 60-mm or below on a 100-mm VAS (visual analogue scale) Patients with adequate blood coagulation activity: PT(INR) < 1.5, APTT <1.5×control Patients with adequate renal function: Creatinine ≤ 2.0 ㎎/㎗, levels of proteinuria measured with Dipstick: trace or less Patients with adequate hepatic function: Bilirubin ≤ 2.0 ㎎/㎗, AST/ALT ≤ 100 IU/L Patients who have received no surgery or radiation therapy in the affected joint within the past 6 six weeks, and have recovered from the side effects of such past treatments Female patients of childbearing potential must agree to practice adequate methods of birth control to prevent pregnancy during the study Patients whose physical examination results show no ligament instability of Grade II or above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm) Patients who voluntarily agreed to enroll in the study and signed an informed consent form Exclusion Criteria: Patients with autoimmune disease or the medical history Patients with infections requiring parenteral administration of antibiotics Patients with myocardial infarction, ischemic heart failure, other serious heart conditions or uncontrolled hypertension, or any medical history of such diseases Patients with serious internal diseases Patients who are currently pregnant or nursing Patients with psychotic diseases, epilepsy, or any history of such diseases Patients with alcohol abuse Patients who smoke excessively Patients with chronic inflammatory articular diseases such as rheumatoid arthritis Patients who were enrolled in any other clinical trials within the past four weeks Patients who had been administered with immunosuppressants such as Cyclosporin A or azathioprine within the past six weeks Patients whose physical examination results show ligament instability of Grade II or above (Grade 0: none, Grade I: 0-5 mm, Grade II: 5-10 mm, Grade III: >10 mm) Patients with a known history of hypersensitivity/allergy to gentamicin Patients whom the principal investigator considers inappropriate for the clinical trial 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CARTISTEM<br>A single dose of 500㎕/㎠ of cartilage defect | Biological: CARTISTEM<br>* A single dose of 500㎕/㎠ of cartilage defect<br>* Other names: hUCB-MSCs;|
| Active Comparator: Microfracture<br>conventional treatment method | Procedure: Microfracture<br>* Active control<br>* Other names: Conventional surgical treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of improvement in knee assessments compared to the active control (microfracture) | Knee assessments will be performed using the following tools: IKDC (International Knee Documentation Committee) Pain score on VAS (Visual Analogue Scale) WOMAC (Western Ontario and McMaster Universities Arthritis Index) | 36 months, 48 months, and 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Systemic and local adverse events especially attributable to the implanted cells will be assessed. General physical examinations: vital signs, blood tests Physical assessments of the knee: swelling, tenderness, pain, range of motion Tumor formation at the implantation site: radiological evaluation using MRI(T1(dGEMRIC)and T2 mapping) | 36 months, 48 months, and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Umbilical Cord Blood, Mesenchymal Stem Cells, Cartilage injury, Osteoarthritis