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

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

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.

Study Overview

• Status: Completed
• Conditions: Chondral or Osteochondral Lesion of Talus
• Intervention / Treatment: Biological: CARTISTEM®; Procedure: Microfracture

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Dongdaemun-gu
    • Seoul, Dongdaemun-gu, Korea, Republic of, 02447
      • KyungHee University Medical Center
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06351
      • Samsung Medical Center
    • Seoul, Gangnam-gu, Korea, Republic of, 06273
      • Gangnam Severance Hospital
  • Guro-gu
    • Seoul, Guro-gu, Korea, Republic of, 08308
      • Korea University Guro Hospital
  • Jung-gu
    • Daejeon, Jung-gu, Korea, Republic of, 35015
      • Chungnam National University Hospital
    • Incheon, Jung-gu, Korea, Republic of, 22332
      • Inha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microfracture + CARTISTEM®; CARTISTEM® is added on the lesion as a single dose of 500 ㎕/㎠ according to the defect size after arthroscopic curettage and microfracture.	Biological: CARTISTEM®; *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)
Active Comparator: Microfracture; Standard treatment of arthroscopic curettage and microfracture is performed for cartilage defect.	Procedure: Microfracture; *Stratified randomization by lesion size below 1.5㎠ or more than 1.5㎠ 1. Procedure: Microfracture

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hyundai Bioland Co., Ltd.
• Collaborators: Medipost Co Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Actual): June 13, 2022
• Study Completion (Actual): June 13, 2022

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 27, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Mesenchymal stem cell; MSC; Talus; OLT; Chondral Lesion; Osteochondral Lesion; Human umbilical cord blood-derived stem cell
• Other Study ID Numbers: CARTISTEM_2019_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will not be shared to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No