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

Phase 3

Completed

• Conditions: Chondral or Osteochondral Lesion of Talus
• Interventions: Biological: CARTISTEM®; Procedure: Microfracture

• Registration Number: NCT04310215
• Lead Sponsor: Hyundai Bioland Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-03-03
• Study First Submitted: 2020-03-12
• Study First Submitted QC: 2020-03-16
• Study First Posted: 2020-03-17
• Primary Completion: 2022-06-13
• Study Completion: 2022-06-13
• Status Verified: 2022-08
• Last Update Submitted: 2022-11-27
• Last Update Posted: 2022-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

1. Talar chondral/osteochondral lesion confirmed by radiographical exam at screening or diagnosis, an AOFAS score of 75 or below

2. Ankle joint pain/stiffness with no response to conservative treatment for more than 12 weeks

3. Ankle joint cartilage injury of defect of ICRS grade Ⅳ in MRI

4. Male or female aged more than 18

5. A one-sided lesion

6. Appropriate function of blood clot: PT(INR) < 1.5×ULN, aPTT <1.5×ULN

7. Appropriate renal function: Creatinine ≤ 2.0 ㎎/㎗, Proteinuria ≤ trace

8. Appropriate hepatic function: Total bilirubin ≤ 2.0 ㎎/㎗, AST/ALT ≤ 100 IU/L

9. 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)

10. No surgery or radiotherapy for the same ankle joint within 6 weeks

11. 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.

12. No chronic ligament instability more than grade Ⅲ (Grade 0: none, Grade Ⅰ: 1~5㎜, GradeⅡ: 5~10㎜, Grade Ⅲ: >10㎜)

13. Patients agreeing with participation in this study and signed on informed consent by their own will

Exclusion Criteria

1. Degenerative arthritis in ankle(Kellgren Lawrence Grade 3-4)

2. Autoimmune disease

3. Infectious disease need to administration of parenteral antibiotics

4. Myocardial infarction, congestive heart failure, other serious cardiac disorder or uncontrolled resistant hypertension

5. 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.

6. Pregnancy or breast-feeding

7. Psychiatric history or epilepsy

8. Alcohol abuse

9. Heavy smoker

10. Chronic inflammatory disease such as rheumatoid arthritis

11. Participants other clinical trials within 4 weeks

12. Administration of immunosuppressing agents such as Cyclosporin A or azathioprine within 6 weeks

13. Patients with acute ligament injury and clinically significant chronic ligament instability

14. Patients treated with surgery or cell therapy product for the same disease

15. Patients with hypersensitivity or allergy history to bovine protein, hyaluronic acid and gentamicin

16. Other inappropriate patients determined by the principal investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Microfracture + CARTISTEM®	CARTISTEM®	CARTISTEM® is added on the lesion as a single dose of 500 ㎕/㎠ according to the defect size after arthroscopic curettage and microfracture.
Microfracture	Microfracture	Standard treatment of arthroscopic curettage and microfracture is performed for cartilage defect.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
ICRS-Cartilage Repair Assessment Overall Grade	Week 48	The grades range from 1(normal) to 4 (severely abnormal) where lower grades indicate more complete repair
Improvement degree of Cartilage Repair by MRI	Week 0 and 48	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
Degree of Functional improvement in FAOS(Foot & Ankle Outcome Score)	Week 0, 24 and 48	: 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
Degree of Functional improvement in AOFAS(The American Orthopaedic Foot & Ankle Score)	Week 0, 24 and 48	: 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
Degree of Functional improvement in Tegner activity score	Week 0, 24 and 48	: 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
Degree of Quality of Life improvement in SF-36(Short Form Health Survey-36)	Week 0, 24 and 48	: 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
Degree of pain improvement in 100 mm VAS(Visual Analogue Scale)	Week 0, 24 and 48	* VAS represents higher scores mean higher pain; * 0 mm (no pain) and 100 mm (worst pain)

Trial Locations

Locations (6)

Samsung Medical Center; 🇰🇷 Seoul, Gangnam-gu, Korea, Republic of

Kyunghee University Medical Center; 🇰🇷 Seoul, Dongdaemun-gu, Korea, Republic of

Gangnam Severance Hospital; 🇰🇷 Seoul, Gangnam-gu, Korea, Republic of

Chungnam National University Hospital; 🇰🇷 Daejeon, Jung-gu, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Guro-gu, Korea, Republic of

Inha University Hospital; 🇰🇷 Incheon, Jung-gu, Korea, Republic of