Trial Outcomes & Findings for Extension Study for Participants of MACI00206 Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Knee (NCT NCT01251588)

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.

Recruitment status

COMPLETED

Target enrollment

128 participants

Primary outcome timeframe

MACI00206 Baseline to Week 156

Results posted on

2021-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	MACI autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture Microfracture: Arthroscopic Microfracture
Overall Study STARTED	65	63
Overall Study COMPLETED	65	59
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Extension Study for Participants of MACI00206 Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture	Total n=128 Participants Total of all reporting groups
Age, Continuous	34.4 years STANDARD_DEVIATION 8.94 • n=99 Participants	32.7 years STANDARD_DEVIATION 8.80 • n=107 Participants	33.6 years STANDARD_DEVIATION 8.88 • n=206 Participants
Sex: Female, Male Female	25 Participants n=99 Participants	21 Participants n=107 Participants	46 Participants n=206 Participants
Sex: Female, Male Male	40 Participants n=99 Participants	42 Participants n=107 Participants	82 Participants n=206 Participants
Region of Enrollment Czech Republic	9 participants n=99 Participants	7 participants n=107 Participants	16 participants n=206 Participants
Region of Enrollment Netherlands	28 participants n=99 Participants	30 participants n=107 Participants	58 participants n=206 Participants
Region of Enrollment Sweden	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Region of Enrollment Norway	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment Poland	13 participants n=99 Participants	12 participants n=107 Participants	25 participants n=206 Participants
Region of Enrollment United Kingdom	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment France	8 participants n=99 Participants	7 participants n=107 Participants	15 participants n=206 Participants

PRIMARY outcome

Timeframe: MACI00206 Baseline to Week 156

Population: The analysis population (n=128) consists of a subpopulation of participants enrolled in the SUMMIT study (n=144). 65 of 65 MACI treated patients and 57 of 63 microfracture-treated patients completed the KOOS at Week 156.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=57 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores. Change from Baseline in KOOS Pain	42.14 units on a scale Interval -36.1 to 83.3	35.77 units on a scale Interval -2.8 to 83.3
Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores. Change from Baseline in KOOS Function	45.63 units on a scale Interval -20.0 to 95.0	36.95 units on a scale Interval -23.8 to 100.0

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: Analysis population includes all participants who completed each KOOS subscale at Week 260.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=59 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline for the Participant's KOOS Pain and Function (Sports and Recreational Activities) Scores Change from Baseline in KOOS Pain	45.17 units on a scale Interval 0.0 to 83.3	38.42 units on a scale Interval -11.1 to 88.9
Change From MACI00206 Baseline for the Participant's KOOS Pain and Function (Sports and Recreational Activities) Scores Change from Baseline in KOOS Function	47.17 units on a scale Interval -10.0 to 95.0	37.56 units on a scale Interval -20.0 to 100.0

SECONDARY outcome

Timeframe: Week 260

Population: all participants with an MRI at Week 260

MRI was assessed by the independent blinded evaluators by means of consensus. The number of participants with a degree of defect fill of \>50% is reported.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=55 Participants Microfracture: Arthroscopic Microfracture
Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill	44 Participants	39 Participants

SECONDARY outcome

Timeframe: Up to week 260

A 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 MACI00206 Baseline scores.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores	51 Participants	46 Participants

SECONDARY outcome

Timeframe: Years 2 through 5 post treatment (MACI or microfracture)

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 ACI.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 260 weeks

ANALYSIS NOT DONE: The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. The number of per protocol treatment failures in each treatment group are reported here. 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 ACI.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
Average Time to Treatment Failure	1 Participants	1 Participants

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: Analysis population includes all participants who completed each KOOS subscale at Week 260.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=59 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS Change from Baseline Activities of Daily Living	42.82 units on a scale Interval -8.8 to 82.4	35.86 units on a scale Interval -20.6 to 89.7
Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS Change from Baseline Quality of Life	39.9 units on a scale Interval -18.8 to 93.8	34.53 units on a scale Interval -37.5 to 100.0
Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS Change from Baseline Other Symptoms	32.53 units on a scale Interval -7.1 to 78.6	28.45 units on a scale Interval -14.3 to 89.3

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: 64 of the 65 MACI-treated patients and 59 of the 63 microfracture-treated patients enrolled in MACI00809 completed the IKDC form at Week 260.

The IKDC Subjective Knee Evaluation Form is a validated knee-specific measure of symptoms, function, and sports activity that is appropriate for patients with a wide variety of knee problems. The form consists of 18 items covering the domains of symptoms, functioning during activities of daily living and sports, and current function of the knee. The IKDC Subjective Knee Evaluation Form is scored by summing the scores for the individual items and then transforming the score to a scale that ranges from 0 to 100. The transformed score is interpreted as a measure of function such that higher scores represent higher levels of function and lower levels of symptoms. A score of 100 is interpreted to mean no limitation with activities of daily living or sports activities and the absence of symptoms.

Outcome measures

Outcome measures
Measure	MACI n=64 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=59 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form	35.48 units on a scale Interval -11.5 to 80.5	31.58 units on a scale Interval -21.8 to 85.1

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: 65 of the 65 MACI-treated patients and 59 of the 63 microfracture-treated patients enrolled in MACI00809 completed the Modified Cincinnati Knee Rating System at Week 260.

The Modified Cincinnati Knee Rating System is a self-assessment of the intensity of sports participation, functional limitations, and the ability to participate in different types of sports. The Modified Cincinnati Knee Rating System overall knee condition score ranges from 1 (poor) to 10 (excellent).

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=59 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System	3.55 units on a scale Interval -1.0 to 8.0	2.71 units on a scale Interval -3.0 to 8.0

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: 65 of the 65 MACI-treated patients and 55 of the 63 microfracture-treated patients enrolled in MACI00809 completed the 12-Item Short-Form Health Survey at Week 260.

The SF-12 is a subset of the 36-Item Short-Form Health Survey (SF-36) and includes 8 subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are used to calculate the physical (PCS) and mental (MCS) summary component scores. MCS and PCS are summarized as Z-scores using standard SF-12 scoring and a US population means. The Z-score indicates how many standard deviations a score is from the population mean. Higher values reflect better health. Changes from Baseline are reported.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=55 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores Change from Baseline in Physical Component Score	1.52 Z-score Interval -1.6 to 4.0	1.28 Z-score Interval -1.3 to 3.8
Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores Change from Baseline in Mental Component Score	0.38 Z-score Interval -2.2 to 3.3	0.52 Z-score Interval -2.0 to 3.9

SECONDARY outcome

Timeframe: MACI00206 Baseline and Week 260

Population: 65 of the 65 MACI-treated patients and 58 of the 63 microfracture-treated patients enrolled in MACI00809 completed the EQ-5D VAS Score at Week 260.

The EQ-5D is a standardized instrument for use as a measure of health outcome (see the EuroQOL Website for details: www.euroqol.org). Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. The EQ Visual Analogue Scale (VAS) was used to record the respondents' self-rated health status on a vertical graduated (0-100) VAS where 0 is 'the worst health you can imagine' and 100 is 'the best health you can imagine'.

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=58 Participants Microfracture: Arthroscopic Microfracture
Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score	20.14 units on a scale Interval -15.0 to 68.0	17.1 units on a scale Interval -40.0 to 85.0

SECONDARY outcome

Timeframe: Years 2 through 5 post treatment (MACI or microfracture)

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)	49 Participants	47 Participants

SECONDARY outcome

Timeframe: Years 2 through 5 post treatment (MACI or microfracture)

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
Number of Participants Reporting Serious Adverse Events (SAEs)	16 Participants	17 Participants

SECONDARY outcome

Timeframe: Years 2 through 5 post treatment (MACI or microfracture)

Outcome measures

Outcome measures
Measure	MACI n=65 Participants autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 Participants Microfracture: Arthroscopic Microfracture
Number of Participants Having Subsequent Surgical Procedures (SSPs) in Target Knee	7 Participants	6 Participants

Adverse Events

MACI

Serious events: 16 serious events

Other events: 49 other events

Deaths: 0 deaths

Microfracture

Serious events: 17 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	MACI n=65 participants at risk autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 participants at risk Microfracture: Arthroscopic Microfracture
Musculoskeletal and connective tissue disorders Arthralgia	44.6% 29/65 • Years 2 through 5 post treatment (MACI or microfracture)	50.8% 32/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Tendonitis	6.2% 4/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Back Pain	4.6% 3/65 • Years 2 through 5 post treatment (MACI or microfracture)	6.3% 4/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Osteoarthritis	3.1% 2/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Joint Effusion	3.1% 2/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Procedural Pain	3.1% 2/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Ligament sprain	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Infections and infestations Nasopharyngitis	10.8% 7/65 • Years 2 through 5 post treatment (MACI or microfracture)	3.2% 2/63 • Years 2 through 5 post treatment (MACI or microfracture)
Infections and infestations Influenza	6.2% 4/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Nervous system disorders Headache	16.9% 11/65 • Years 2 through 5 post treatment (MACI or microfracture)	20.6% 13/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Cartilage Injury	4.6% 3/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)

Additional Information

Ann Remmers, Senior Director, Clinical Science

Vericel Corporation

Phone: 734-428-4526

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	MACI n=65 participants at risk autologous cultured chondrocytes on porcine collagen membrane: Implantation	Microfracture n=63 participants at risk Microfracture: Arthroscopic Microfracture
Injury, poisoning and procedural complications Cartilage Injury	3.1% 2/65 • Years 2 through 5 post treatment (MACI or microfracture)	11.1% 7/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Osteoarthritis	4.6% 3/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
General disorders Treatment Failure	4.6% 3/65 • Years 2 through 5 post treatment (MACI or microfracture)	7.9% 5/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Graft delamination	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Meniscus Injury	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Procedural pain	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Tendon rupture	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Transplant failure	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Contusion	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Head injury	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Pancreatic injury	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Arthropathy	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Ligament laxity	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Bone disorder	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Chondropathy	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Joint lock	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	3.2% 2/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
General disorders Impaired healing	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	3.2% 2/63 • Years 2 through 5 post treatment (MACI or microfracture)
Ear and labyrinth disorders Otosclerosis	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Gastrointestinal disorders Gastric haemorrhage	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Gastrointestinal disorders Gastric stenosis	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Gastrointestinal disorders Inguinal hernia	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Infections and infestations Erysipelas	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Vascular disorders Varicose vein	1.5% 1/65 • Years 2 through 5 post treatment (MACI or microfracture)	0.00% 0/63 • Years 2 through 5 post treatment (MACI or microfracture)
Cardiac disorders Cardiac arrest	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Pregnancy, puerperium and perinatal conditions Retained placenta or membranes	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Reproductive system and breast disorders Endometriosis	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)
Musculoskeletal and connective tissue disorders Loose body in joint	0.00% 0/65 • Years 2 through 5 post treatment (MACI or microfracture)	1.6% 1/63 • Years 2 through 5 post treatment (MACI or microfracture)