Clinical trial NCT05051332: Phase 3 Clinical Trial of CartiLife® in Korea
Official title: A Multi-Center, Active-Controlled, Open-Label, Phase III Trial to Compare the Efficacy and Safety for Treatment of Autologous Chondrocytes Implantation With CartiLife Versus Microfracture for Patients With Knee Chondral Defects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Articular Cartilage Defect
Articular Cartilage Degeneration
Lead sponsor: Biosolution Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-21
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigational Group : CartiLife® Procedure: 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 cm\^3 of defect volume, and fibrin adhesive is applied to fix pellets in place through minimal arthrotomy.

Active comparator: Microfracture Surgery Procedure : 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 purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of pellet-type extracellular matrix-associated autologous chondrocytes (CartiLife®) obtained by cultivating costal chondrocytes of the subject implanted into articular cartilage defects of the knee resulting from trauma or degeneration.

Detailed description: This open-label, phase 3 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.

Eligibility criteria: Inclusion Criteria:

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

1. Patients over the age of 18.
2. Defect size: 2 to 10 cm\^2 on the unilateral knee cartilage (up to 4 ㎤ in volume).
3. Defect: isolated ICRS (International Cartilage Repair Society) grade III or IV single defect chondral lesion on articular cartilage with comparatively healthy cartilage present near the lesion site (ICRS Grade 1 \~ 2).
4. Patients with a KOOS total score below 55.
5. Patients able to walk without aid.
6. Patients who agree to abide by rehabilitation protocols and follow-up programs, including residential exercise routines.
7. Patients who provide written consent to the application of the clinical trial.

Exclusion Criteria:

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

1. Patients with inflammatory articular diseases such as rheumatoid arthritis or gouty arthritis.
2. Patients scoring 3 or above on the Kellgren-Lawrence Grading Scale.
3. Patients with inflammatory articular diseases related to autoimmune diseases.
4. Patients hypersensitive to bovine derived proteins or any of the components in this product.
5. Patients hypersensitive to Gentamycin.
6. Patients with Haemophilia or markedly reduced immune function.
7. Patients with arterial bleeding and severe venous bleeding.
8. Patients with other diseases including tumors except for cartilaginous defects of joints.
9. Patients with a history of radiation treatment and chemotherapy within the past two years.
10. Patients who are pregnant, or nursing a baby.
11. Patients who participate in concurrent clinical trials or previous clinical trials within 30 days of administration.
12. Other cases where the investigator deems the patient ineligible for participation.

Primary outcomes:
measure: MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue)
timeFrame: At Week 48, post-operation
measure: KOOS Total Score
timeFrame: From Week 0 to Week 48, post-operation
Secondary outcomes:
measure: MOCART Score
timeFrame: At Week 24 and Week 96, post-operation
measure: Lysholm Score
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: IKDC Score
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: KOOS Score (Pain, Other symptoms, Function in daily living, Function in sport and recreation, and knee-related QOL subscales)
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: VAS (100mm Pain Visual Analogue Scale)
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: Tegner Activity Scale
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: Pain medication history
timeFrame: At Week 0 to Week 8, 24, 48 and 96, post-operation
measure: Treatment related adverse events
timeFrame: At Week 0 (pre-operation), and up to 24 Months (post-operation)
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital (1)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital (2)
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic UNIV. of Korea Seoul St. Mary's Hospital
city: Uijeongbu-si
country: Korea, Republic of
facility: The Catholic UNIV. of Korea Uijeongbu St. Mary's Hospital
Study officials:
affiliation: Biosolution Co., Ltd.
name: Jungsun Lee, Ph.D
role: STUDY_DIRECTOR
affiliation: Kyung Hee University Hospital
name: Kyoung Ho Yoon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ewha Womans University Mokdong Hospital
name: Jae Doo Yoo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kyung Hee University Hospital at Gangdong
name: Sang Hak Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gangnam Severance Hospital
name: Sung-Hwan Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Ji Hoon Bae, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Hyuk-Soo Han, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Samsung Medical Center
name: Joon Ho Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Severance Hospital
name: Min Jung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Catholic UNIV. of Korea Seoul St. Mary's Hospital
name: Yong In, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital (1)
name: Chong Bum Chang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital (2)
name: Yong Seuk Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Catholic UNIV. of Korea Uijeongbu St. Mary's Hospital
name: Seok Jung Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonnam National University Hospital
name: Jong Geun Seon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chosun University Hospital
name: Dong Hwi Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chungnam National University Hospital
name: Young-Mo Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan National University Hospital
name: Seung Joon Rhee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Haeundae Paik Hospital, Inje University
name: Sang Won Moon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kosin University Gospel Hospital
name: Young Choi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yoon KH, Park JY, Lee JY, Lee E, Lee J, Kim SG. Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defect. Am J Sports Med. 2020 Apr;48(5):1236-1245. doi: 10.1177/0363546520905565. Epub 2020 Mar 3.
citation: Yoon KH, Yoo JD, Choi CH, Lee J, Lee JY, Kim SG, Park JY. Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation versus Microfracture for Repair of Articular Cartilage Defects: A Prospective Randomized Trial. Cartilage. 2021 Dec;13(1_suppl):1092S-1104S. doi: 10.1177/1947603520921448. Epub 2020 Jun 1.