Trial Outcomes & Findings for Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee (NCT NCT00719576)
NCT ID: NCT00719576
Last Updated: 2021-05-12
Results Overview
The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score.
COMPLETED
PHASE3
144 participants
Baseline and Week 104
2021-05-12
Participant Flow
Participant milestones
| Measure |
MACI
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Overall Study
STARTED
|
72
|
72
|
|
Overall Study
COMPLETED
|
70
|
67
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee
Baseline characteristics by cohort
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
|
Total
n=144 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.8 years
STANDARD_DEVIATION 9.16 • n=113 Participants
|
32.9 years
STANDARD_DEVIATION 8.78 • n=163 Participants
|
33.8 years
STANDARD_DEVIATION 9.00 • n=160 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=113 Participants
|
24 Participants
n=163 Participants
|
51 Participants
n=160 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=113 Participants
|
48 Participants
n=163 Participants
|
93 Participants
n=160 Participants
|
|
Region of Enrollment
Czech Republic
|
13 participants
n=113 Participants
|
11 participants
n=163 Participants
|
24 participants
n=160 Participants
|
|
Region of Enrollment
Netherlands
|
28 participants
n=113 Participants
|
30 participants
n=163 Participants
|
58 participants
n=160 Participants
|
|
Region of Enrollment
Sweden
|
1 participants
n=113 Participants
|
1 participants
n=163 Participants
|
2 participants
n=160 Participants
|
|
Region of Enrollment
Norway
|
3 participants
n=113 Participants
|
3 participants
n=163 Participants
|
6 participants
n=160 Participants
|
|
Region of Enrollment
Poland
|
14 participants
n=113 Participants
|
14 participants
n=163 Participants
|
28 participants
n=160 Participants
|
|
Region of Enrollment
United Kingdom
|
4 participants
n=113 Participants
|
4 participants
n=163 Participants
|
8 participants
n=160 Participants
|
|
Region of Enrollment
France
|
9 participants
n=113 Participants
|
9 participants
n=163 Participants
|
18 participants
n=160 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 104Population: All randomized patients
The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score.
Outcome measures
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores.
Change from Baseline KOOS Pain
|
45.45 units on a scale
Standard Deviation 21.08
|
35.23 units on a scale
Standard Deviation 23.91
|
|
Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores.
Change from Baseline KOOS Function
|
46.04 units on a scale
Standard Deviation 28.35
|
35.83 units on a scale
Standard Deviation 31.63
|
SECONDARY outcome
Timeframe: Week 104Population: includes all subjects with histology follow-up data
The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint. Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage.
Outcome measures
| Measure |
MACI
n=60 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=56 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104
|
63.8 units on a scale
Interval 0.0 to 95.0
|
62.3 units on a scale
Interval 7.0 to 97.0
|
SECONDARY outcome
Timeframe: Week 104Population: Number of participants with MRI data at Week 104
Number of participants with MRI degree of defect fill \> 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment. Appropriate MRI sequences were used to image cartilage repair tissue.
Outcome measures
| Measure |
MACI
n=70 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=69 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Assessment of Defect Fill by Magnetic Resonance Imaging (MRI)
|
58 Participants
|
53 Participants
|
SECONDARY outcome
Timeframe: Week 104A responder is defined as a participant with at least a 10-point improvement in both the KOOS Pain and Function (Sports and Recreational activities) scores from Baseline
Outcome measures
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104.
|
63 Participants
|
49 Participants
|
SECONDARY outcome
Timeframe: Week 104The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported. Patients were considered as a treatment failure if all of the following 5 criteria were met: 1. Patient's global assessment of their knee joint compared to Baseline was the same or worse 2. Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse. 3. Percent improvement from Baseline in KOOS Pain score was less than 10%. 4. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion. 5. The physician decided that surgical re-treatment of the index lesion(s) was required that involved either extensive debridement for lesion expansion, violation of the subchondral bone, or autologous cultured chondrocyte implantation.
Outcome measures
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Treatment Failure
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 104The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems).
Outcome measures
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms)
Change from Baseline in Activities of Daily Living
|
43.70 units on a scale
Standard Deviation 24.52
|
32.76 units on a scale
Standard Deviation 26.78
|
|
Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms)
Change from Baseline in KOOS Quality of Life
|
37.41 units on a scale
Standard Deviation 27.24
|
29.93 units on a scale
Standard Deviation 28.11
|
|
Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms)
Change from Baseline in KOOS Other Symptoms
|
35.47 units on a scale
Standard Deviation 20.83
|
27.31 units on a scale
Standard Deviation 24.59
|
SECONDARY outcome
Timeframe: Week 104Outcome measures
| Measure |
MACI
n=72 Participants
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 Participants
Microfracture
Microfracture: Microfracture
|
|---|---|---|
|
Participants With Treatment-Emergent Adverse Events
|
55 Participants
|
60 Participants
|
Adverse Events
MACI
Microfracture
Serious adverse events
| Measure |
MACI
n=72 participants at risk
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 participants at risk
Microfracture
|
|---|---|---|
|
Cardiac disorders
Arrhythmia
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
General disorders
Impaired healing
|
1.4%
1/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
General disorders
Treatment failure
|
1.4%
1/72 • Week 104
|
5.6%
4/72 • Week 104
|
|
Infections and infestations
Pneumonia
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Infections and infestations
Wound infection staphylococcal
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Injury, poisoning and procedural complications
Cartilage injury
|
2.8%
2/72 • Week 104
|
8.3%
6/72 • Week 104
|
|
Injury, poisoning and procedural complications
Graft delamination
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
2.8%
2/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Injury, poisoning and procedural complications
Transplant failure
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Injury, poisoning and procedural complications
Traumatic fracture
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/72 • Week 104
|
4.2%
3/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Joint lock
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Knee deformity
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Loose body in joint
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Patellofemoral pain syndrome
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Nervous system disorders
Multiple sclerosis
|
0.00%
0/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
1.4%
1/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Renal and urinary disorders
Urinary retention
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.4%
1/72 • Week 104
|
1.4%
1/72 • Week 104
|
|
Vascular disorders
Thrombosis
|
1.4%
1/72 • Week 104
|
0.00%
0/72 • Week 104
|
Other adverse events
| Measure |
MACI
n=72 participants at risk
autologous cultured chondrocytes on porcine collagen membrane
|
Microfracture
n=72 participants at risk
Microfracture
|
|---|---|---|
|
General disorders
Pyrexia
|
5.6%
4/72 • Week 104
|
2.8%
2/72 • Week 104
|
|
Infections and infestations
Influenza
|
5.6%
4/72 • Week 104
|
6.9%
5/72 • Week 104
|
|
Infections and infestations
Nasopharyngitis
|
13.9%
10/72 • Week 104
|
9.7%
7/72 • Week 104
|
|
Injury, poisoning and procedural complications
Procedural pain
|
4.2%
3/72 • Week 104
|
5.6%
4/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
8/72 • Week 104
|
9.7%
7/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
6.9%
5/72 • Week 104
|
5.6%
4/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
9.7%
7/72 • Week 104
|
5.6%
4/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Ligament sprain
|
2.8%
2/72 • Week 104
|
5.6%
4/72 • Week 104
|
|
Nervous system disorders
Headache
|
18.1%
13/72 • Week 104
|
29.2%
21/72 • Week 104
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/72 • Week 104
|
6.9%
5/72 • Week 104
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
51.4%
37/72 • Week 104
|
63.9%
46/72 • Week 104
|
Additional Information
Ann Remmers, Senior Director, Clinical Science
Vericel Corporation
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60