Efficacy and Safety of Allogenic Stem Cell Product(CARTISTEM®) for Osteochondral Lesion of Talus

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of adding CARTISTEM®(allogenic umbilical cord blood-derived stem cell product) on microfracture, a currently standard treatment for OLT, in patients with talar chondral or osteochondral defect.

Official Title
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A Multi-center, Single-blind, Randomized, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Adding CARTISTEM® on Microfracture in Patients With Talar Chondral or Osteochondral Defect

Conditions
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Chondral or Osteochondral Lesion of Talus

Intervention / Treatment
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* Biological: CARTISTEM®
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Talar chondral/osteochondral lesion confirmed by radiographical exam at screening or diagnosis, an AOFAS score of 75 or below Ankle joint pain/stiffness with no response to conservative treatment for more than 12 weeks Ankle joint cartilage injury of defect of ICRS grade Ⅳ in MRI Male or female aged more than 18 A one-sided lesion Appropriate function of blood clot: PT(INR) < 1.5×ULN, aPTT <1.5×ULN Appropriate renal function: Creatinine ≤ 2.0 ㎎/㎗, Proteinuria ≤ trace Appropriate hepatic function: Total bilirubin ≤ 2.0 ㎎/㎗, AST/ALT ≤ 100 IU/L No evidence of auto-immune disorder: According to investigator's judgement based on relevent symtom and physical exam, anti-nuclear antibody and anti-thyroglobulin antibody tests are able to performed and confirmed negative (If positive, there are possible cases according to diagnostic opinion of medical department) No surgery or radiotherapy for the same ankle joint within 6 weeks Female patients agreeing with maintenance of contraception* during study period *hormone contraceptive, implants of intrauterine device or intrauterine system, double barrier contraception[Concurrent use of diaphragm or cervical occlusive cap and male condom], surgical sterilisation, etc. No chronic ligament instability more than grade Ⅲ (Grade 0: none, Grade Ⅰ: 1 5㎜, GradeⅡ: 5 10㎜, Grade Ⅲ: >10㎜) Patients agreeing with participation in this study and signed on informed consent by their own will Exclusion Criteria: Degenerative arthritis in ankle(Kellgren Lawrence Grade 3-4) Autoimmune disease Infectious disease need to administration of parenteral antibiotics Myocardial infarction, congestive heart failure, other serious cardiac disorder or uncontrolled resistant hypertension Serious medical disease(Ex. Kidney disease such as chronic renal failure or Glomerulonephritis, etc., acute/chronic liver disease such as liver cirrhosis, fatty liver etc., medical history of malignancy*) *Complete remission status is possible. Pregnancy or breast-feeding Psychiatric history or epilepsy Alcohol abuse Heavy smoker Chronic inflammatory disease such as rheumatoid arthritis Participants other clinical trials within 4 weeks Administration of immunosuppressing agents such as Cyclosporin A or azathioprine within 6 weeks Patients with acute ligament injury and clinically significant chronic ligament instability Patients treated with surgery or cell therapy product for the same disease Patients with hypersensitivity or allergy history to bovine protein, hyaluronic acid and gentamicin Other inappropriate patients determined by the principal investigator

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
Interventional Model Description: A multicenter, Single-blinded, Stratified randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microfracture + CARTISTEM®<br>CARTISTEM® is added on the lesion as a single dose of 500 ㎕/㎠ according to the defect size after arthroscopic curettage and microfracture. | Biological: CARTISTEM®<br>* *Stratified randomization by lesion size below 1.5㎠ or more than 1.5㎠ Procedure: Microfracture Biological: CARTISTEM®(Human Umbilical Cord Blood-derived Mesenchymal Stem Cell product)<br>|
| Active Comparator: Microfracture<br>Standard treatment of arthroscopic curettage and microfracture is performed for cartilage defect. | Procedure: Microfracture<br>* *Stratified randomization by lesion size below 1.5㎠ or more than 1.5㎠ 1. Procedure: Microfracture<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICRS-Cartilage Repair Assessment Total Score | Arthroscopic evaluation of articular cartilage repair : The score range from 12(normal) to 1(severely abnormal) where lower scores indicate more severity of injury | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICRS-Cartilage Repair Assessment Overall Grade | The grades range from 1(normal) to 4 (severely abnormal) where lower grades indicate more complete repair | Week 48 | 
| Improvement degree of Cartilage Repair by MRI | Changes in MOCART(Magnetic resonance Observation of Cartilage Repair Tissue) score : MOCART score is a 9-part and 29-item scoring system, also resulting in a find cartilage repair tissue score between 0 and 100 points. 100 points represent the best imaginable score | Week 0 and 48 | 
| Degree of Functional improvement in FAOS(Foot & Ankle Outcome Score) | : FAOS consists in 42 items that cover 5 dimensions (symptoms, pain, activities of daily living, sport and recreation activities, and quality of life. Raw scores of each sub-scales results of the sum of each items. A normalized score (100 indicationg no symptoms and 0 indicating extreame sysmptoms) is calculated for each subscale | Week 0, 24 and 48 | 
| Degree of Functional improvement in AOFAS(The American Orthopaedic Foot & Ankle Score) | : AOFAS consists in 9 items that can be divided into 3 sub-scales (pain, function and alignment). 100 points of 1 to 100 represent no symptoms or impairments | Week 0, 24 and 48 | 
| Degree of Functional improvement in Tegner activity score | : Tegner activity represents the highest level of activity on scale of 0 to 10 that you are able to participate in currently . The higher values represent a better outcome | Week 0, 24 and 48 | 
| Degree of Quality of Life improvement in SF-36(Short Form Health Survey-36) | : SF-36 comprises 36 items divided into two components of physical health and mental health. Higher scores between 0 and 100 represent better health status | Week 0, 24 and 48 | 
| Degree of pain improvement in 100 mm VAS(Visual Analogue Scale) | VAS represents higher scores mean higher pain 0 mm (no pain) and 100 mm (worst pain) | Week 0, 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OLT, Talus, Chondral Lesion, Osteochondral Lesion, Human umbilical cord blood-derived stem cell, MSC, Mesenchymal stem cell