Clinical trial NCT04744402: Phase 2 Clinical Trial of CartiLife® in the United States
Official title: A Multi-Center, Open-Label, Phase 2 Trial to Evaluate the Efficacy and Safety of CartiLife® for Patients With Articular Cartilage Defects in the Knee
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Articular Cartilage Defect
Articular Cartilage Degeneration
Lead sponsor: Biosolution Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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®) 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.

Eligibility 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 60 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) ≤ 37 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 6 weeks (Subjects can be considered enrollment per the investigator's discretion)
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%

Primary outcomes:
measure: Change in KOOS (Knee Injury and Osteoarthritis Outcome Score) function (sports and recreational activities)
timeFrame: Week 0 (pre-operation) to Week 48 (post-operation)
measure: Change in volume fill of cartilage defect score
timeFrame: Week 0 (pre-operation) to Week 48 (post-operation)
Secondary outcomes:
measure: Change in Lysholm Score
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in IKDC (International Knee Documentation Committee) Score
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in KOOS (Knee injury Osteoarthritis Outcome Score) subscale scores (Pain, Other symptoms, Function in daily living, and knee-related Quality of Life)
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in KOOS (Knee injury Osteoarthritis Outcome Score) Total Score
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in VAS (100mm Pain Visual Analogue Scale)
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in Tegner Activity Score
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) Score
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Evaluations of MOCART Score
timeFrame: Week 24 and 48 (post-operation)
measure: Evaluation of T2 mapping
timeFrame: Week 24 and 48 (post-operation)
measure: Change in pain medication dosage
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Change in pain medication frequency
timeFrame: Week 0 (pre-operation) to Week 8, 24 and 48 (post-operation)
measure: Number of subjects with treatment-related adverse events
timeFrame: Week 0 (pre-operation), and up to 24 Months (post-operation)
measure: Number of subjects with treatment-emergent serious adverse events
timeFrame: Week 0 (pre-operation), and up to 24 Months (post-operation)
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Tilda Research
state: California
city: La Mesa
country: United States
facility: Biosolutions Clinical Research Center
state: California
city: La Mesa
country: United States
facility: Horizon Clinical Research
state: California
city: Lafayette
country: United States
facility: Lafayette General Health
state: Louisiana
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Biosolution Co., Ltd.
name: Jungsun Lee, Ph.D
role: STUDY_DIRECTOR
References: