Phase 3 Clinical Trial of CartiLife® in Korea

A Multi-Center, Active-Controlled, Open-Label, Phase III Trial to Compare the Efficacy and Safety for Treatment of Autologous Chondrocytes Implantation With CartiLife Versus Microfracture for Patients With Knee Chondral Defects

To evaluate the safety and efficacy of pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) obtained by cultivating costal chondrocytes of the subject implanted into articular cartilage defects of the knee resulting from trauma or degeneration.

Study Overview

• Status: Active, not recruiting
• Conditions: Articular Cartilage Defect; Articular Cartilage Degeneration
• Intervention / Treatment: Drug: Autologous Chondrocyte Implantation (CartiLife®); Procedure: Microfracture Surgery

Detailed Description

This open-label, phase 3 study is being conducted to evaluate the safety and efficacy of pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) compared with microfracture surgery in adults with articular cartilage defects due to trauma or degeneration of the knee. It is hypothesized that CartiLife® treatment will demonstrate structural regeneration and improvement in function and pain at Week 48 compared to baseline.

• Study Type: Interventional
• Enrollment (Anticipated): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Inje university Haeundae Paik Hospital
  • Busan, Korea, Republic of, 49267
    • Kosin University Gospel Hospital
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Gwangju, Korea, Republic of, 61453
    • Chosun university hospital
  • Gwangju, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Pusan, Korea, Republic of, 35015
    • Pusan National University Hospital
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital (1)
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital (2)
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of, 07985
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05278
    • Kyung Hee University Hospital at Gangdong
  • Seoul, Korea, Republic of, 06230
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 16591
    • The Catholic Univ. of Korea Seoul St. Mary's Hospital
  • Uijeongbu-si, Korea, Republic of, 11765
    • The Catholic UNIV. of Korea Uijeongbu St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following:

1. Patients over the age of 18.
2. Defect size: 2 to 10 cm^2 on the unilateral knee cartilage (up to 4 ㎤ in volume).
3. Defect: isolated ICRS (International Cartilage Repair Society) grade III or IV single defect chondral lesion on articular cartilage with comparatively healthy cartilage present near the lesion site (ICRS Grade 1 ~ 2).
4. Patients with a KOOS total score below 55.
5. Patients able to walk without aid.
6. Patients who agree to abide by rehabilitation protocols and follow-up programs, including residential exercise routines.
7. Patients who provide written consent to the application of the clinical trial.

Exclusion Criteria:

Individuals who meet any of the following will be excluded from participation in this study:

1. Patients with inflammatory articular diseases such as rheumatoid arthritis or gouty arthritis.
2. Patients scoring 3 or above on the Kellgren-Lawrence Grading Scale.
3. Patients with inflammatory articular diseases related to autoimmune diseases.
4. Patients hypersensitive to bovine derived proteins or any of the components in this product.
5. Patients hypersensitive to Gentamycin.
6. Patients with Haemophilia or markedly reduced immune function.
7. Patients with arterial bleeding and severe venous bleeding.
8. Patients with other diseases including tumors except for cartilaginous defects of joints.
9. Patients with a history of radiation treatment and chemotherapy within the past two years.
10. Patients who are pregnant, or nursing a baby.
11. Patients who participate in concurrent clinical trials or previous clinical trials within 30 days of administration.
12. Other cases where the investigator deems the patient ineligible for participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CartiLife®; Extracellular matrix-associated autologous chondrocytes comprise CartiLife®, composed as pellets (1.1 to 1.8 mm in diameter) in suspension. One pre-filled syringe is implanted per 1 cm^3 of defect volume, and fibrin adhesive is applied to fix pellets in place through minimal arthrotomy.	Drug: Autologous Chondrocyte Implantation (CartiLife®); CartiLife consists of small beads (1 mm in diameter) in suspension, developed from pellet culture of autologous costal chondrocytes after multiplication. The beads are implanted in an injective manner with fibrin glue through minimal arthrotomy. The dose depends on the size (volume) of the defect, recommended dose is 480 pellets/cm^3 defect; Other Names: CartiLife
Active Comparator: Microfracture Surgery; Microfracture surgery, performed by arthroscopy after the joint is cleaned of calcified cartilage, will be conducted using an awl or drill to create tiny fractures in the subchondral bone plate.	Procedure: Microfracture Surgery; Microfracture surgery, performed by arthroscopy after the joint is cleaned of calcified cartilage, will be conducted using an awl or drill to create tiny fractures in the subchondral bone plate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue)	MOCART is a validated tool that provides reliable, reproducible, and accurate assessment of cartilage repair tissue (Marlovits et al, 2006 that; Trattnig et al, 2011).	At Week 48, post-operation
KOOS Total Score	The KOOS is a reliable and valid patient-reported outcome measurement tool that evaluates both short-term and long-term consequences of knee injury. The 5 separately scored subscales of Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related QOL may enrich clinical and research data interpretation (Roos and Lohmander, 2003; Collins et al, 2011). In the 'Knee injury and Osteoarthritis Outcome Score', scores range from 0 to 100 with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms.	From Week 0 to Week 48, post-operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MOCART Score	MOCART is a validated tool that provides reliable, reproducible, and accurate assessment of cartilage repair tissue (Marlovits et al, 2006 that; Trattnig et al, 2011). In the 'Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score', the total score ranges from 0 to 100, with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms.	At Week 24 and Week 96, post-operation
Lysholm Score	The Lysholm scale is a broadly applicable, validated tool for measuring changes following nonsurgical and surgical intervention, as well as deterioration over time in patients with various knee pathologies (Collins et al, 2011). In the 'Lysholm score', the total score ranges from 0 to 100, with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms.	At Week 0 to Week 8, 24, 48 and 96, post-operation
IKDC Score	The IKDC Knee form covers domains likely to be important to patients and has adequate consistency and broad applicability across mixed groups of patients (Collins et al, 2011). In the 'International Knee Documentation Committee Subjective Knee Form', the total score ranges from 0 to 100, with a score of 0 indicating the worst knee symptoms(lowest level of function or highest level of symptoms) and 100 indicating no knee symptoms(highest level of function and lowest level of symptoms).	At Week 0 to Week 8, 24, 48 and 96, post-operation
KOOS Score (Pain, Other symptoms, Function in daily living, Function in sport and recreation, and knee-related QOL subscales)	The KOOS is a reliable and valid patient-reported outcome measurement tool that evaluates both short-term and long- term consequences of knee injury. The 5 separately scored subscales of Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related QOL may enrich clinical and research data interpretation (Roos and Lohmander, 2003; Collins et al, 2011). KOOS Score (Pain, Other symptoms, Function in daily living, Function in sport and recreation, and knee-related QOL subscales) are measured between 0, 1, 2, 3 and 4. The KOOS subscales are scored separately: Pain (9 items); Symptoms (7 items); Function in daily living (17 items); Function in sport and recreation (5 items); knee-related QOL (4 items). Each scale is scored between 0 to 4. The total score ranges from 0 to 100, with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms.	At Week 0 to Week 8, 24, 48 and 96, post-operation
VAS (100mm Pain Visual Analogue Scale)	The VAS is a validated, ubiquitous tool for patient-reported measurement of pain at a given point in time (Kersten et al, 2014). Visual Analogue Scale (VAS) is a measurement instrument that measures a specified characteristic which is deemed difficult to quantify across a continuous line of value to determine its representative value. The VAS scale ranges from 0 to 100 mm, with 0 indicating absence of pain and 100 indicating the worst pain experienced.	At Week 0 to Week 8, 24, 48 and 96, post-operation
Tegner Activity Scale	The Tegner activity score is a frequently used patient-administered activity rating system for patients with various knee activity functions. The instrument scores a person's activity level between 0 and 10 where 0 is 'on sick leave/disability' and 10 is 'participation in competitive sports such as soccer at a national or international elite level' (Karen Hambly, 2011). A level of 0 indicates that the patient is unable to participate in activities barring 'Sick leave or disability pension because of knee problems', and a level of 10 indicates that the patient is capable of participating in activities which at its most intense include 'Competitive sports - soccer, football, rugby at a national elite level'.	At Week 0 to Week 8, 24, 48 and 96, post-operation
Pain medication history	Pain medication history is an indicator of patient pain. Pain medication history is an indicator of patient pain. The frequency of analgesic ingestion is measured for the specified duration over the course of the clinical trial, and changes in analgesic ingestion in terms of frequency are assessed to analyze the efficacy of the clinical trial product.	At Week 0 to Week 8, 24, 48 and 96, post-operation
Treatment related adverse events	Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms, abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination results. The total number of patients who exhibit symptoms identified as an adverse event will be cumulatively combined to obtain a whole digit number representing the number of patients who have suffered an adverse event throughout the course of the clinical trial.	At Week 0 (pre-operation), and up to 24 Months (post-operation)

Collaborators and Investigators

• Sponsor: Biosolution Co., Ltd.
• Investigators: Study Director: Jungsun Lee, Ph.D, Biosolution Co., Ltd.; Principal Investigator: Kyoung Ho Yoon, MD, Kyung Hee University Hospital; Principal Investigator: Sang Hak Lee, MD, Kyung Hee University Hospital at Gangdong; Principal Investigator: Sung-Hwan Kim, MD, Gangnam Severance Hospital; Principal Investigator: Ji Hoon Bae, MD, Korea University Guro Hospital; Principal Investigator: Hyuk-Soo Han, MD, Seoul National University Hospital; Principal Investigator: Joon Ho Wang, MD, Samsung Medical Center; Principal Investigator: Min Jung, MD, Severance Hospital; Principal Investigator: Yong In, MD, The Catholic Univ. of Korea Seoul St. Mary's Hospital; Principal Investigator: Chong Bum Chang, MD, Seoul National University Bundang Hospital (1); Principal Investigator: Yong Seuk Lee, MD, Seoul National University Bundang Hospital (2); Principal Investigator: Seok Jung Kim, MD, The Catholic UNIV. of Korea Uijeongbu St. Mary's Hospital; Principal Investigator: Jong Geun Seon, MD, Chonnam National University Hospital; Principal Investigator: Dong Hwi Kim, MD, Chosun university hospital; Principal Investigator: Young-Mo Kim, MD, Chungnam National University Hospital; Principal Investigator: Seung Joon Rhee, MD, Pusan National University Hospital; Principal Investigator: Sang Won Moon, MD, Haeundae paik hospital, inje university; Principal Investigator: Young Choi, MD, Kosin University Gospel Hospital

Publications and helpful links

General Publications

• Yoon KH, Park JY, Lee JY, Lee E, Lee J, Kim SG. Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defect. Am J Sports Med. 2020 Apr;48(5):1236-1245. doi: 10.1177/0363546520905565. Epub 2020 Mar 3.
• Yoon KH, Yoo JD, Choi CH, Lee J, Lee JY, Kim SG, Park JY. Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation versus Microfracture for Repair of Articular Cartilage Defects: A Prospective Randomized Trial. Cartilage. 2021 Dec;13(1_suppl):1092S-1104S. doi: 10.1177/1947603520921448. Epub 2020 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2020
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: BS-CTL-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are no future plans to share the IPD at this time.

Study Data/Documents

1. Clinical Study Report
   Information identifier: NCT03545269
   Information comments: Study to Assess the Efficacy and Safety of Treatment of Articular Cartilage Lesions With CartiLife®
2. Clinical Study Report
   Information identifier: NCT03517046
   Information comments: Study to Assess the Safety of Treatment of Articular Cartilage Lesions With CartiLife®

Drug and device information, study documents

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