Back to resultsEvaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects
Primary Purpose
Degeneration Articular Cartilage Knee
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CARTISTEM®
Sponsored by
About this trial
This is an interventional treatment trial for Degeneration Articular Cartilage Knee focused on measuring human umbilical cord blood-derived mesenchymal stem cells, MSC, cartilage lesion, cartilage defect, degenerative arthritis, stem cell implantation
Eligibility Criteria
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
Sites / Locations
- Cartilage Restoration Center; RUSH University Medical Center
- Cartilage Repair Center; Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CARTISTEM®
Arm Description
Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect
Outcomes
Primary Outcome Measures
IKDC Score
Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.
The outcome was presented with the post-operative change amount from the baseline.
Secondary Outcome Measures
VAS
Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.
Lysholm Score
The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
KOOS Score
The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from "never/not at all" to "always/extremely." The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
IKDC Score
Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01733186
Brief Title
Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 7, 2013 (Actual)
Primary Completion Date
June 2, 2017 (Actual)
Study Completion Date
August 29, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medipost Co Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Degeneration Articular Cartilage Knee
Keywords
human umbilical cord blood-derived mesenchymal stem cells, MSC, cartilage lesion, cartilage defect, degenerative arthritis, stem cell implantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CARTISTEM®
Arm Type
Experimental
Arm Description
Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect
Intervention Type
Biological
Intervention Name(s)
CARTISTEM®
Other Intervention Name(s)
human umbilical cord blood-derived mesenchymal stem cells
Primary Outcome Measure Information:
Title
IKDC Score
Description
Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.
The outcome was presented with the post-operative change amount from the baseline.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
VAS
Description
Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.
Time Frame
24 months
Title
Lysholm Score
Description
The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
Time Frame
24 months
Title
KOOS Score
Description
The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from "never/not at all" to "always/extremely." The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
Time Frame
24 months
Title
IKDC Score
Description
Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian J Cole, MD
Organizational Affiliation
Cartilage Restoration Center, Rush University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andreas H Gomoll, MD
Organizational Affiliation
Cartilage Repair Center, Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cartilage Restoration Center; RUSH University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Cartilage Repair Center; Brigham and Women's Hospital
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
http://clinicaltrials.gov/ct2/show/NCT01041001?term=cartistem&rank=2
Description
Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect
Learn more about this trial
Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects
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