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

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.

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.

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.

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.

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.

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.

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.

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).

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.

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'.