Phase 2 Clinical Trial of CartiLife® in the United States

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). The score is from 0 to 100, with 0 representing extreme problems and 100 representing no problems.

The IKDC (International Knee Documentation Committee) 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). The score is from 0 to 100, with 0 representing extreme problems and 100 representing no problems.

The KOOS (Knee injury Osteoarthritis Outcome Score) 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). The score is from 0 to 100, with 0 representing extreme problems and 100 representing no problems.

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). The score is from 0 to 100, with 0 representing extreme problems and 100 representing no problems.

The VAS is a validated, ubiquitous tool for patient-reported measurement of pain at a given point in time (Kersten et al, 2014). The score is from 0 to 100, with 0 representing no pain and 100 representing extreme pain.

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).

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints (Jose M. 2006). The score is from 0 to 100, with 0 representing no problems and 100 representing extreme problems.

MOCART provides a reliable, reproducible, and accurate method of assessment of cartilage repair tissue. The total score is determined by adding the following subscale scores :

1. Volume fill of cartilage defect (0~20 points, 20:Complete filling, 0:<25% filling of total defect volume)
2. Integration into adjacent cartilage (0~15 points, 15:Complete integration, 0:Integrated cartilage interface ≥50% of repair tissue length)
3. Surface of the repair tissue (0~10 points, 10:Surface intact, 0:≥50% surface irregularity)
4. Structure of the repair tissue (0~10 points, 10:Homogenous, 0:Inhomogenous)
5. Signal intensity of the repair tissue (0~15 points, 15:Normal, 0:Severely abnormal)
6. Bony defect or bony overgrowth (0~10 points, 10:No bony defect or overgrowth, 0:Bony defect, depth ≥ thickness or overgrowth ≥50% of adjacent cartilage)
7. Subchondral changes (0 ~ 20 points, 20:No major changes, 0:Subchondral cyst ≥5 mm in longest diameter OR osteonecrosis-like signal)

In vivo, the visualization of collagen architecture, and possibly the maturation of this architecture over time in cartilage repair tissue, can be seen when assessing the spatial variation of T2 values. Histologically validated animal studies report this increase in zonal T2 as an indicator of hyaline or ''hyaline-like'' cartilage composition. T2 evaluation is more sensitive in revealing changes in articular cartilage and cartilage repair tissue compared to morphological analysis using thickness measurements or the MOCART score. (Mamisch et al, 2010)

Pain medication history is an indicator of patient pain. The amount of analgesic ingestion is measured for the specified duration over the course of the clinical trial, and changes in analgesic ingestion are assessed to analyze the efficacy of the clinical trial product.

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.

Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms, and abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination results

Number of subjects with treatment-emergent serious adverse events defined as one or more of the following untoward medical occurrences happening during study period.

• Life-threatening event (e.g., stroke or non-fatal pulmonary embolism).
• Requires inpatient hospitalization or prolongation of existing hospitalization.
• Results in persistent or significant disability/incapacity.
• Results in death.
• Leads to other clinically significant untoward laboratory test result(s) or medical condition(s), determined per Investigator's judgement.