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

An Extension Protocol for Participants of Genzyme-Sponsored Prospective, Randomized, Open-Label, Parallel-Group, Multicenter Study of MACI® for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01251588

Acronym

Extension

Enrollment

128

Registered

2010-12-02

Start date

2010-12-31

Completion date

2015-03-31

Last updated

2021-05-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Articular Cartilage Defects

Keywords

Cartilage legions, Symptomatic focal cartilage defects, Microfracture, MACI, Autologous chondrocyte

Brief summary

To examine the 5-year efficacy and safety of MACI implant, compared with arthroscopic microfracture, in participants who received study treatment in the SUMMIT study for treatment of symptomatic articular cartilage defects of the knee.

Detailed description

This study was an open-label, multicenter extension to the SUMMIT study designed to examine the 5-year efficacy and safety of MACI compared to arthroscopic microfracture in the treatment of articular cartilage defects of the knee in participants who received study treatment in the SUMMIT study. Follow-up to 2 years post-study treatment was completed as part of the SUMMIT study. Follow-up from 3 to 5 years post-study treatment in SUMMIT was completed in this extension study. All 144 participants who received study treatment in the SUMMIT study were eligible for enrollment into this extension study. Participants had until the end of the visit window for the last visit of this extension study (ie, Week 260 + 6 weeks) to consent to enter this extension study. Efficacy and safety assessments were performed at scheduled visits 3, 4, and 5 years following treatment in SUMMIT (ie, at Weeks 156, 208, and 260 postarthrotomy for patients treated with MACI implant or at Weeks 156, 208, and 260 postarthroscopy for patients treated with microfracture).

Interventions

BIOLOGICALautologous cultured chondrocytes on porcine collagen membrane

Implantation received in the previous MACI00206 study

PROCEDUREMicrofracture

Arthroscopic Microfracture treatment received in the previous MACI00206 study

Study design

Observational model

OTHER

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

Randomized and received study treatment (MACI or microfracture) in the SUMMIT study.

Design outcomes

Primary

Measure	Time frame	Description
Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores.	MACI00206 Baseline to Week 156	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.

Secondary

Measure	Time frame	Description
Change From MACI00206 Baseline for the Participant's KOOS Pain and Function (Sports and Recreational Activities) Scores	MACI00206 Baseline and Week 260	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.
Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill	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.
The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures	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.
Average Time to Treatment Failure	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.
Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS	MACI00206 Baseline and Week 260	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.
Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form	MACI00206 Baseline and 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.
Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores	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.
Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores	MACI00206 Baseline and 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.
Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score	MACI00206 Baseline and 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'.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)	Years 2 through 5 post treatment (MACI or microfracture)	—
Number of Participants Reporting Serious Adverse Events (SAEs)	Years 2 through 5 post treatment (MACI or microfracture)	—
Number of Participants Having Subsequent Surgical Procedures (SSPs) in Target Knee	Years 2 through 5 post treatment (MACI or microfracture)	—
Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System	MACI00206 Baseline and 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).

Countries

Czechia, France, Netherlands, Norway, Poland, Sweden, United Kingdom

Participant flow

Participants by arm

Arm	Count
MACI autologous cultured chondrocytes on porcine collagen membrane: Implantation	65
Microfracture Microfracture: Arthroscopic Microfracture	63
Total	128

Baseline characteristics

Characteristic	Microfracture	Total	MACI
Age, Continuous	32.7 years STANDARD_DEVIATION 8.8	33.6 years STANDARD_DEVIATION 8.88	34.4 years STANDARD_DEVIATION 8.94
Region of Enrollment Czech Republic	7 participants	16 participants	9 participants
Region of Enrollment France	7 participants	15 participants	8 participants
Region of Enrollment Netherlands	30 participants	58 participants	28 participants
Region of Enrollment Norway	3 participants	6 participants	3 participants
Region of Enrollment Poland	12 participants	25 participants	13 participants
Region of Enrollment Sweden	1 participants	2 participants	1 participants
Region of Enrollment United Kingdom	3 participants	6 participants	3 participants
Sex: Female, Male Female	21 Participants	46 Participants	25 Participants
Sex: Female, Male Male	42 Participants	82 Participants	40 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	49 / 65	46 / 63
serious Total, serious adverse events	16 / 65	17 / 63

Outcome results

Primary

Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores.

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)
MACI	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
MACI	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
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	35.77 units on a scale
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 Function	36.95 units on a scale

Secondary

Average Time to Treatment Failure

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.

Time frame: Up to 260 weeks

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
MACI	Average Time to Treatment Failure	1 Participants
Microfracture	Average Time to Treatment Failure	1 Participants

Secondary