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Phase 2 Clinical Trial of CartiLife® in the United States

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ClinicalTrials.gov Identifier: NCT04744402
Recruitment Status : Recruiting
First Posted : February 9, 2021
Last Update Posted : March 23, 2021
Sponsor:
Information provided by (Responsible Party):
Biosolution Co., Ltd.

Brief Summary:
To evaluate the safety and efficacy of implanting pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) obtained by cultivating costal chondrocytes of the subject with articular cartilage defects of the knee as a result of trauma or degeneration.

Condition or disease Intervention/treatment Phase
Articular Cartilage Defect Articular Cartilage Degeneration Drug: Autologous Chondrocyte Implantation (CartiLife®) Procedure: Microfracture Surgery Phase 2

Detailed Description:
This open-label, phase 2 study is being conducted to evaluate the safety and efficacy of pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) compared with microfracture surgery in adults with articular cartilage defects due to trauma or degeneration of the knee. It is hypothesized that CartiLife® treatment will demonstrate structural regeneration and improvement in function and pain at Week 48 compared to baseline.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Investigational group: CartiLife® Extracellular matrix-associated autologous chondrocytes comprise CartiLife®, composed as pellets (1.1 to 1.8 mm in diameter) in suspension. One pre-filled syringe is implanted per 1 cm3 of defect volume, and fibrin adhesive is applied to fix pellets in place through minimal arthrotomy.

Active comparator: Microfracture surgery Microfracture surgery, performed by arthroscopy after the joint is cleaned of calcified cartilage, will be conducted using an awl or drill to create tiny fractures in the subchondral bone plate.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Active-Controlled, Open-Label, Phase 2 Trial to Compare the Efficacy and Safety of CartiLife®, and Microfracture for Patients With Articular Cartilage Defects in the Knee
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: CartiLife®
Extracellular matrix-associated autologous chondrocytes comprise CartiLife®, composed as pellets (1.1 to 1.8 mm in diameter) in suspension. One pre-filled syringe is implanted per 1 cm3 of defect volume, and fibrin adhesive is applied to fix pellets in place through minimal arthrotomy.
Drug: Autologous Chondrocyte Implantation (CartiLife®)
CartiLife consists of small beads (1 mm in diameter) in suspension, developed from pellet culture of autologous costal chondrocytes after multiplication. The beads are implanted in an injective manner with fibrin glue through minimal arthrotomy. The dose depends on the size (volume) of the defect, recommended dose is 480 pellets/cm^3 defect
Other Name: CCP-ACI

Active Comparator: Microfracture surgery
Microfracture surgery, performed by arthroscopy after the joint is cleaned of calcified cartilage, will be conducted using an awl or drill to create tiny fractures in the subchondral bone plate.
Procedure: Microfracture Surgery
Microfracture surgery, performed by arthroscopy after the joint is cleaned of calcified cartilage, will be conducted using an awl or drill to create tiny fractures in the subchondral bone plate.




Primary Outcome Measures :
  1. Change in KOOS (Knee Injury and Osteoarthritis Outcome Score) function (sports and recreational activities) [ Time Frame: Week 0 (pre-operation) to Week 48 (post-operation) ]
    The KOOS (Knee Injury and 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 ranges from 0 to 100, with 0 representing extreme problems and 100 representing no problems.

  2. Change in volume fill of cartilage defect score [ Time Frame: Week 0 (pre-operation) to Week 48 (post-operation) ]
    Volume fill of cartilage defect score from MOCART 2.0 Criteria (Schreiner, et al, 2019). The score is from 0 to 20, with 0 representing "<25% filling of total defect volume OR complete delamination in situ" and 20 representing "Complete fill OR minor hypertrophy (100% to 150% filling of total defect volume).


Secondary Outcome Measures :
  1. Change in Lysholm Score [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  2. Change in IKDC (International Knee Documentation Committee) Score [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  3. Change in KOOS (Knee injury Osteoarthritis Outcome Score) subscale scores (Pain, Other symptoms, Function in daily living, and knee-related Quality of Life) [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  4. Change in KOOS (Knee injury Osteoarthritis Outcome Score) Total Score [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  5. Change in VAS (100mm Pain Visual Analogue Scale) [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  6. Change in Tegner Activity Score [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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).

  7. Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) Score [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  8. Evaluations of MOCART Score [ Time Frame: Week 24 and 48 (post-operation) ]

    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)

  9. Evaluation of T2 mapping [ Time Frame: Week 24 and 48 (post-operation) ]
    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)

  10. Change in pain medication dosage [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  11. Change in pain medication frequency [ Time Frame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation) ]
    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.

  12. Number of subjects with treatment-related adverse events [ Time Frame: Week 0 (pre-operation), and up to 24 Months (post-operation) ]
    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

  13. Number of subjects with treatment-emergent serious adverse events [ Time Frame: Week 0 (pre-operation), and up to 24 Months (post-operation) ]

    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following:

  1. Male or female subjects aged over 18 at the time of signing the Informed Consent form
  2. Subject who has a size of the relevant cartilage lesion ≥ 2 cm2 and ≤ 10 cm2 but with a defect area total volume ≤ 4 cm3
  3. Subject with isolated International Cartilage Repair Society (ICRS) Grade III or IV chondral lesion on articular cartilage
  4. Subject who has a lower extremity alignment within 5 degrees of the neutral weight bearing axis
  5. Subject who can move independently and has a mechanically stable knee (normal ligament status)
  6. Subject with intact or partial meniscus status (>50% of meniscus)
  7. Subject who has KOOS pain value less than 55 at baseline
  8. Subject who agrees to actively participate in a rehabilitation protocol and follow-up program
  9. Subject who is able to provide informed consent and comply with study requirements
  10. Subject who is willing to discontinue any nonsteroidal anti-inflammatory drugs (NSAIDs) except rescue medication (< acetaminophen 4 g per day) 7 days prior to visit
  11. Subject who has Body Mass Index (BMI) ≤ 35 kg/m2
  12. Female and male subjects of childbearing potential who are willing to use adequate contraception methods for the duration of the trial.

Exclusion Criteria:

Individuals who meet any of the following will be excluded from participation in this study:

  1. Subject who has inflammatory articular diseases such as rheumatoid arthritis or gout or pseudogout
  2. Subject who has radiographic evidence of grade 4 osteoarthritis based on the Kellgren and Lawrence criteria
  3. Subject who has received an intra-articular treatment within the last 3 months
  4. Subject who has had a surgical procedure on the knees within the last 2 months
  5. Subject who has a condition in another lower extremity joint that interferes with the function of the index knee
  6. Subject who would receive a concomitant surgical procedure on the knees at the time of the study treatment
  7. Subject whose articular cartilage defect is asymptomatic
  8. Subject who has any clinically significant disease, which is judged by the investigator to affect this clinical trial, including but not limited to diabetes not adequately controlled, bleeding diathesis or hematologic disease, endocrinopathies, cardiovascular disease, renal disease (severe renal impairment), autoimmune disease, inflammatory arthritis, and current infectious disease
  9. Subject with other diseases including tumors except for cartilaginous defects of joints
  10. Subject who has a history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
  11. Subject who participates in concurrent trials or in previous trial within 30 days of signing informed consent
  12. Subject who has any radiation therapy or chemotherapy within 2 years prior to screening
  13. Subject who is currently pregnant or nursing
  14. Subject who has any degenerative muscular, connective tissue or neurological condition or other disease process that would interfere with healing or the evaluation of outcome measures.
  15. Subject with known HIV infection, active hepatitis C and/or hepatitis B infection
  16. Subject who has ligament instability > Grade 1
  17. Subject who is an active drug/alcohol abuser or has a history of alcohol or drug abuse during the last two years.
  18. Subject who has significant lab abnormalities for the following parameters (If the value is within 10% of the listed laboratory exclusion criterion value and the value is considered not to be clinically significant by the investigator, the subject can be considered for enrollment):

    • Serum ALT and AST > 3 x upper limit of normal
    • Serum creatinine > 1.5 x upper limit of normal
    • PT/INR out of normal range
    • Hemoglobin < 10 g/dL for female subject and hemoglobin < 11 g/dL for male subject
    • Platelets out of normal range
    • Hemoglobin A1c levels > 9%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04744402


Contacts
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Contact: Minkyu Woo, B.A +82234468884 ext 6620 christinelee@kcrnresearch.com
Contact: Jungsun Lee, Ph.D +82234468884 ext 6603 dvmljs@biosolutions.co.kr

Locations
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United States, California
Biosolutions Clinical Research Center Recruiting
La Mesa, California, United States, 91942
Contact: Tamara Packard    619-637-0770    tamara@biosolutionsresearch.com   
Principal Investigator: Peter Hanson, MD         
Horizon Clinical Research Recruiting
La Mesa, California, United States, 91942
Contact: Dino Subasic    619-456-6012    dino@horizontrials.com   
Principal Investigator: Scott Hacker, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Angela Pedroza    614-293-7952    Angela.Pedroza@osumc.edu   
Principal Investigator: David Flanigan, MD         
Sponsors and Collaborators
Biosolution Co., Ltd.
Investigators
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Study Director: Jungsun Lee, Ph.D Biosolution Co., Ltd.
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Responsible Party: Biosolution Co., Ltd.
ClinicalTrials.gov Identifier: NCT04744402    
Other Study ID Numbers: BS-CTL-II
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: March 23, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share IPD at this point.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cartilage Diseases
Musculoskeletal Diseases
Connective Tissue Diseases