Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects

Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects: A Phase I/IIa Clinical Trial in Patients With Focal, Full-thickness Grade 3-4 Articular Cartilage Defects of the Knee

The purpose of this study is to determine whether CARTISTEM, a cell therapeutic product, is safe and effective in the treatment of articular cartilage defects of the knee as a result of ageing, trauma, or degenerative diseases.

Conventional treatment modalities have not been able to provide complete and sustained resolution of symptoms following damage to the articular cartilage. Despite the numerous techniques available today, complete healing of damaged or defective cartilage or consistent reproduction of normal hyaline cartilage does not occur, and continuous drug administration or secondary surgeries are common.

Research in mesenchymal stem cells has had a rapid acceleration over the past decade and MSC-based therapy has become one of the objects of investigation for a new branch of medicine termed regenerative medicine. This emerging technology shows great promise for producing transplantable cartilage constructs to restore the function of degenerated joints.

CARTISTEM®, a combination of human umbilical cord blood-derived mesenchymal stem cells and sodium hyaluronate, is intended to be used as a single-dose cellular therapeutic agent for cartilage regeneration in human subjects with cartilage defects of the knee as a result of ageing, trauma, or degenerative diseases.

Inclusion Criteria:

• Patients with an intended- to- treat single focal, full-thickness cartilage defect (ICRS [International Cartilage Repair Society] Grade 3 or 4) of the knee as a result of ageing, trauma, or degenerative diseases.
• Age ≥ 18 years old
• Size of the articular cartilage lesion is ≥ 2 cm2
• Swelling, tenderness and active range of motion ≤ Grade II
• Joint pain : 20-mm - 60-mm on VAS (Visual Analog Scale) at the time of Screening
• Appropriate blood coagulation, kidney and liver function laboratory parameters: PT(INR) < 1.5, APTT <1.5×control Creatinine ≤ 2.0 mg/dL Albumin ≤ trace in urine dipstick test Bilirubin ≤ 2.0 mg/dL, AST/ALT ≤ 100 IU/L
• Ligament instability ≤ Grade II
• Lower extremity alignment within 5 degrees of the neutral weight bearing axis
• No meniscal surgery within the past 3 months and more than 5mm of meniscal rim remaining
• Ability and willingness to fully participate in the post-operative rehabilitation program
• Subject is informed of the investigational nature of this study, voluntarily agrees to participate in the study, and signs an IRBapproved informed consent prior to performing any of the screening procedures
• Body Mass Index (BMI) ≤ 35 kg/m2

Exclusion Criteria:

• Patients who have been treated previously and are asymptomatic
• Avascular necrosis/ osteonecrosis
• Autoimmune or inflammatory joint disease
• History of infection within the past 6 weeks
• Surgery or radiation therapy within the past 6 weeks
• Serious medical co-morbidities, which would otherwise contraindicate surgery, as determined by the investigator
• Currently pregnant or nursing
• Psychotic diseases, epilepsy, or any history of such diseases
• Current abuse of alcohol (> 10 drinks weekly) and/or regular exposure to other substances of abuse, currently an active smoker
• Chronic inflammatory articular diseases such as rheumatoid arthritis
• Enrolled in any other clinical trials within the past 4 weeks
• Administered immunosuppressants such as Cyclosporin A or azathioprine within the past 6 weeks
• Ligament instability > Grade II
• Uncorrected significant lower extremity malalignment (i.e. > 5 degrees)
• (sub-) Total meniscectomy (<5mm rim remaining)
• Corticosteroid or viscosupplementation injection to the affected knee in the past 3 months
• Principal investigator considers inappropriate for the clinical trial due to any reasons other than those listed above