Articular Cartilage Defects of Ankle Joint
Conditions
Keywords
articular cartilage defects, ACI, ankle joint, chondron
Brief summary
An open clinical trial transplanting CHONDRON (autologous chondrocytes) to ankle cartilage defect patients who are appropriate for the trial, and evaluating the validity and safety for 12 months.
Detailed description
This clinical trial was designed to observe effects of CHONDRON (autologous chondrocytes) for 12 months in patients with ankle cartilage defects. In this clinical trial, 30 subjects were screened- 4 were excluded half way and 26 finished the trial. Full-thickness articular cartilage specimen was obtained from sites that do not have direct articulation within the ankle joint(anterior talus, anterior process of calcaneus, calcaneocuboid joint area.) Gel-type CHONDRON (Fibrin mixed Autologous chondrocytes) was transplanted at the defects. Evaluation variables were AOFAS, 100 mm VAS, HANNOVER score, self-assessment of improvement by the patient, MRI and arthroscopy.
Interventions
PROCEDUREChondron(autologous chondrocyte) Implantation
* Test drug: Chondron (more than 12 million chondrocytes in 0.4ml, i.e. 1 vial) * Directions and dosage: Suspend the cells in the vial sufficiently, and implant them in the defective part, making sure that sufficient amounts are injected. \*30 subjects participated in this open clinical trial. Those who agreed to participate voluntarily went through screening to confirm the appropriateness for the clinical trial, and then received Gel type CHONDRON (fibrin mixed autologous chondrocytes) transplantation.
Sponsors
Sewon Cellontech Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. adult men and women over 15 and less than 65 years of age 2. applied to patients with arthroscopically or grossly confirmed, partial cartilage defect at the ankle joint 3. patients with ankle-tibia malalignment of the ankle joint, unstable ankle ligaments, bone defects at the cartilage defect area or patients who received correction in advance. 4. patients which surrounding cartilage are normal 5. patients who agreed to clinical trial participation voluntarily or by the will of the person in parental authority, and signed the written consent form
Exclusion criteria
1. patients hypersensitive to bovine protein 2. patients hypersensitive to gentamicin antibiotics 3. patients with inflammatory arthritis such as rheumatoid arthritis, gout arthritis 4. patients with arthritis related to autoimmune disease 5. pregnant, breast-feeding patients or those who have a possibility of pregnancy 6. patients with accompanying diseases other than articular cartilage defects, including tumors 7. patients who have a history of receiving radiotherapy, chemotherapy in the last 2 years 8. patients with diabetes (however, patients whose blood sugar test results are normal and do not have any complication of diabetes, when a written opinion that CHONDRON administration is possible is appended by a doctor are excluded) 9. patients who are administering antibiotics and antimicrobial agents due to infection 10. patients who receive steroid hormone therapy 11. Patients with psychiatric disorder and those who are considered to be inappropriate for this trial by the judgment of the clinical trial manager
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in American Orthopedic Foot and Ankle Society(AOFAS) at 12 Months Post-surgery | baseline(preoperative stage),12months post-surgery | AOFAS scores(best score-100,worst score- 0 ) 1. pain-none:40/Strong and Always present:O 2. Function * activities-without support activities:10/need restrain, clutch , walker or wheelchair:0 * Maximum gait distance- more than 6:5/ less than 1:0 * gait surface-easy in any surace:5/strong difficult in irregular ground stair or slopes:0 * Gait abnormality-none:8/marked:0 * saggital mobidity- normal or minimal restrain:6/strong restraint:0 * hindfoot mobidity -normal minimal restrain:6/strong restrain:0 * ankle and hindfoot stability - stable:8/unstable:0 3. alignment- good:10/bad:0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in 100mm Visual Analogue Scale(VAS) at 12months Post-surgery | baseline(preoperative stage),12months post-surgery | A VAS is a horizontal line, 100mm in length, anchored by word descriptors about pain at each end.The VAS is measured degree of pain from 0mm to 100mm. Severe pain is represented by 100mm and no pain is represented by 0mm. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks. The difference of secondary evaluation variables VAS at baseline and after the end of the trial were analyzed by using paired t-test. Improvements were compared and analysis by each time point. |
| Average Change From Baseline in the Modified Hannover Scoring System at 12 Months Post Surgery | baseline(preoperative stage),12months post-surgery | The Modified Hannover Score System contains information about patient's status(pain-36, clinical finding- 4, patient's subjective assessment- 25, statics- 6, fuction- 26, radiology-7;best score-104, worst score-0).The scores of 27 patients in the FAS group were taken in the screening period (Visit S), 12 months after transplantation (Visit 7). The difference of the scores at screening and 12 months after transplantation was compared by using the paired t-test. Improvements were compared and analyzed at each time point. |
Countries
South Korea
Participant flow
Recruitment details
30 subjects who have ankle cartilage defects
Participants by arm
| Arm | Count |
|---|---|
| Chondron Implantation Those who agreed to participate voluntarily went through screening to confirm the appropriateness for the clinical trial, and then received appropriate amounts(by size, but mean:4vail(1.6ml)) of CHONDRON (autologous chondrocytes) transplantation. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | patient's refusal | 2 |
Baseline characteristics
| Characteristic | Chondron Implantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age Continuous | 36.67 years STANDARD_DEVIATION 11.44 |
| Region of Enrollment Korea, Republic of | 30 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
Average Change From Baseline in American Orthopedic Foot and Ankle Society(AOFAS) at 12 Months Post-surgery
AOFAS scores(best score-100,worst score- 0 ) 1. pain-none:40/Strong and Always present:O 2. Function * activities-without support activities:10/need restrain, clutch , walker or wheelchair:0 * Maximum gait distance- more than 6:5/ less than 1:0 * gait surface-easy in any surace:5/strong difficult in irregular ground stair or slopes:0 * Gait abnormality-none:8/marked:0 * saggital mobidity- normal or minimal restrain:6/strong restraint:0 * hindfoot mobidity -normal minimal restrain:6/strong restrain:0 * ankle and hindfoot stability - stable:8/unstable:0 3. alignment- good:10/bad:0
Time frame: baseline(preoperative stage),12months post-surgery
Population: Among the 30 patients, 27 who received CHONDRON transplantation became subjects for Full Analysis Set(FAS) analysis, as validity evaluation analysis subjects. The remaining 3 patients were omitted, being excluded from the FAS analysis. (1 subject refused to participate, 2 were unable to do follow-up.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondron Implantation | Average Change From Baseline in American Orthopedic Foot and Ankle Society(AOFAS) at 12 Months Post-surgery | 16.93 scores | Standard Deviation 13.04 |
Secondary
Average Change From Baseline in 100mm Visual Analogue Scale(VAS) at 12months Post-surgery
A VAS is a horizontal line, 100mm in length, anchored by word descriptors about pain at each end.The VAS is measured degree of pain from 0mm to 100mm. Severe pain is represented by 100mm and no pain is represented by 0mm. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks. The difference of secondary evaluation variables VAS at baseline and after the end of the trial were analyzed by using paired t-test. Improvements were compared and analysis by each time point.
Time frame: baseline(preoperative stage),12months post-surgery
Population: Among the 30 patients, 27 who received CHONDRON transplantation became subjects for FAS analysis, as validity evaluation analysis subjects. The remaining 3 patients were omitted, being excluded from the FAS analysis. (1 subject refused to participate, 2 were unable to do follow-up.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondron Implantation | Average Change From Baseline in 100mm Visual Analogue Scale(VAS) at 12months Post-surgery | -27.19 mm | Standard Deviation 31.33 |
Secondary
Average Change From Baseline in the Modified Hannover Scoring System at 12 Months Post Surgery
The Modified Hannover Score System contains information about patient's status(pain-36, clinical finding- 4, patient's subjective assessment- 25, statics- 6, fuction- 26, radiology-7;best score-104, worst score-0).The scores of 27 patients in the FAS group were taken in the screening period (Visit S), 12 months after transplantation (Visit 7). The difference of the scores at screening and 12 months after transplantation was compared by using the paired t-test. Improvements were compared and analyzed at each time point.
Time frame: baseline(preoperative stage),12months post-surgery
Population: Among the 30 patients, 27 who received CHONDRON transplantation became subjects for FAS analysis, as validity evaluation analysis subjects. The remaining 3 patients were omitted, being excluded from the FAS analysis. (1 subject refused to participate, 2 were unable to do follow-up.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondron Implantation | Average Change From Baseline in the Modified Hannover Scoring System at 12 Months Post Surgery | 26.26 scores | Standard Deviation 18.07 |