Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect
The purpose of the study is to assess and compare the safety and efficacy of the allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product (Cartistem®) to that of a microfracture treatment in patients with articular cartilage defect or injury.
Procedure: Microfracture treatment
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized, Open-Label, Multi-Center and Phase 3 Clinical Trial to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect|
- ICRS Cartilage Repair Assessment will follow to determine the appropriate grade. The treatment will be considered efficacious if the ICRS grade drops by at least 1 grade or more from baseline to week 48. [ Time Frame: Week 0 and 48 ] [ Designated as safety issue: No ]
- Degree of improvement in the grade of joint pain measured on a 100-mm VAS (Visual Analogue Scale) [ Time Frame: Week 0, 2, 4, 8, 12, 24, 36 and 48 ] [ Designated as safety issue: Yes ]
- Grade of cartilage regeneration in patients who agreed to a biopsy during arthroscopy at week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
- Changes in WOMAC scores [ Time Frame: Week 0, 2,4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
- Changes in IKDC Subjective Score [ Time Frame: Week 0, 2, 4, 8, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
- ICRS scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Study Completion Date:||January 2011|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
A single dose of 500㎕/㎠ of cartilage defect
allogeneic-unrelated umbilical cord blood-derived mesenchymal stem cell product
|Active Comparator: Microfracture treatment||Procedure: Microfracture treatment|
The cartilage is a unique avascular, aneural tissue that does not regenerate easily once damaged. Chondral defects or damages to articular cartilages due to accidents, necrosis of subchondral bone tissue, or arthritis have become some of the more common disorders today. About 15% of the world's population is reportedly suffering from cartilage and joint damages such as degenerative arthritis and rheumatoid arthritis. As population aging progresses and as more young people start taking up active sports, the size of the target patient group is also growing. However, despite ongoing research, an effective treatment for cartilage defects is yet to be discovered. Various different types of treatments are currently in use, such as drug therapy, arthroscopy, and artificial joint surgery. However, they all fail to address the root cause. Complete treatment, or regeneration of damaged or defective cartilage is impossible and continuous drug administration or secondary surgeries are required in many cases.
As a way of regenerating the damaged or defective cartilage tissue, treatment of localized damage to articular cartilage using autologous chondrocytes is currently under review. A few life science companies both home and abroad are marketing this method of treatment called 'autologous chondrocyte transplant'. The treatment involves the extraction of healthy cartilage tissue from the patient which is then cultured and transplanted into the damaged site.
However, this treatment requires the extraction of chondrocytes directly from the patient and thus causes trauma in healthy articular cartilage. Also, this type of treatment cannot be applied to large lesions, nor is the efficacy satisfactory in patients over the age of 40 whose cellular activation levels are low. Thus, autologous chondrocyte transplant is rather limited in the number of cells harvested and their activation level and is therefore restricted in terms of treatment site, severity of the condition, and the size of lesion. The current technology allows the application of treatments in local cartilage defects but not in degenerative arthritis or rheumatoid arthritis. The technology needs to be taken up to another level in order to benefit such prevalent arthritic disorders. Treatments using stem cells do not cause damage to healthy articular cartilage as they don't require the harvesting of healthy cartilage tissues from the patients. Moreover, the number of successfully cultured cells is larger due to the excellent proliferation capability of stem cells and thus, mass supply is possible.
This clinical trial for the stem cell therapies is essential because treatment of cartilage defects with umbilical cord blood-derived mesenchymal stem cells, known to have the highest level of activity among all adult stem cells, opens the possibility of articular cartilage regeneration even for aged patients and patients with large lesions unable to benefit from existing treatments.
The biggest challenge faced by nations competing in the field of "tissue differentiation and regeneration using stem cells" is the question of whether or not the use of embryonic stem cells is ethical. Chondrogenesis using umbilical cord blood-derived mesenchymal stem cells can not only avoid similar challenges, but also present an innovative treatment mode with significant clinical implications for the patients.
In the clinical study, mesenchymal stem cells will be isolated from umbilical cord blood and cultured, mixed with semi- solid polymer, and administered into the cartilage tissue lesion by orthopedic surgery in order to stimulate the regeneration of defective cartilage tissue and to improve their functions.
|Korea, Republic of|
|Gachon University Gil Hospital|
|Incheon, Gyunggido, Korea, Republic of, 405-760|
|Inha University Hospital|
|Incheon, Korea, Republic of, 400-711|
|Asan Medical Center|
|Seoul, Korea, Republic of, 138-736|
|Seoul Veterans Hospital|
|Seoul, Korea, Republic of, 134-060|
|Ewha Womans University Mokdong Hospital|
|Seoul, Korea, Republic of, 158-710|
|Samsung Medical Center|
|Seoul, Korea, Republic of, 135-710|
|Hanyang University Medical Center|
|Seoul, Korea, Republic of, 133-792|
|Korea University Guro Hospital|
|Seoul, Korea, Republic of, 152-703|
|Principal Investigator:||Hong-chul Lim, MD, PhD||Korea University Guro Hospital|