Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Extension Protocol for Participants of Genzyme-Sponsored Prospective, Randomized, Open-Label, Parallel-Group, Multicenter Study of Matrix-Induced Autologous Chondrocyte Implantation (MACI® implant) for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea

    Summary
    EudraCT number
    		 2009-016970-33
    Trial protocol
    		 NL   CZ   GB   SE   PL  
    Global end of trial date
    18 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Oct 2019
    First version publication date
    04 Oct 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MACI00809
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01251588
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Vericel Corporation
    Sponsor organisation address
    64 Sidney Street, Cambridge, United States, 02139
    Public contact
    Jon Hopper, Vericel Corporation, 01 (617) 588 5702, jhopper@vcel.com
    Scientific contact
    Jon Hopper, Vericel Corporation, 01 (617) 588 5702, jhopper@vcel.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Jun 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Mar 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to examine the 5-year efficacy and safety of Matrix-Induced Autologous Chondrocyte Implantation (MACI® Implant), compared with arthroscopic microfracture, in patients who received study treatment in Genzyme-sponsored study MACI00206 for treatment of symptomatic articular cartilage defects of the femoral condyle, including the trochlea.
    Protection of trial subjects
    This is the extension study with no planned intervention. Patients are followed up for long term safety and efficacy, and provided all necessary medical care.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Dec 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 58
    Country: Number of subjects enrolled
    Norway: 6
    Country: Number of subjects enrolled
    Poland: 25
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Czech Republic: 16
    Country: Number of subjects enrolled
    France: 15
    Worldwide total number of subjects
    128
    EEA total number of subjects
    128
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    128
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 All patients who were treated in the parent study (MACI00206) are offered the opportunity to participate in this extension study.

    Pre-assignment
    Screening details
    		 128 out of 144 patients who were treated in the parent study (MACI00206) consented to participate in this extension study.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MACI
    Arm description
    		 autologous cultured chondrocytes on porcine collagen membrane implant received in previous MACI00206 study
    Arm type
    		 Experimental

    Investigational medicinal product name
    MACI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    autologous cultured chondrocytes on porcine collagen membrane: Implantation, received in the parent study (MACI00206)

    Arm title
    		 Microfracture
    Arm description
    		 Arthroscopic Microfracture treatment received in the previous MACI00206 study
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		MACI Microfracture
    Started
    65
    63
    Completed
    65
    63
    Period 2
    Period 2 title
    Overall
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MACI
    Arm description
    		 autologous cultured chondrocytes on porcine collagen membrane: Implantation
    Arm type
    		 Experimental

    Investigational medicinal product name
    MACI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Autologous cultured chondrocytes on porcine collagen membrane, received study treatment (MACI) in the parent study (MACI00206).

    Arm title
    		 Microfracture
    Arm description
    		 Microfracture: Arthroscopic Microfracture received in the parent study (MACI00206)
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		MACI Microfracture
    Started
    65
    63
    Completed
    65
    59
    Not completed
    0
    4
         Lost to follow-up
    -
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MACI
    Reporting group description
    		 autologous cultured chondrocytes on porcine collagen membrane implant received in previous MACI00206 study

    Reporting group title
    Microfracture
    Reporting group description
    		 Arthroscopic Microfracture treatment received in the previous MACI00206 study

    Reporting group values
    		 MACI Microfracture Total
    Number of subjects
    		 65 63 128
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 65 63 128
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Age at the date of informed consent
    Units: years
        arithmetic mean (standard deviation)
    		 34.4 ± 8.94 32.7 ± 8.80 -
    Gender categorical
    Units: Subjects
        Female
    		 25 21 46
        Male
    		 40 42 82
    Subject analysis sets

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety Analysis

    Subject analysis sets values
    		 Safety Analysis Set
    Number of subjects
    128
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    128
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Age at the date of informed consent
    Units: years
        arithmetic mean (standard deviation)
    33.6 ± 8.88
    Gender categorical
    Units: Subjects
        Female
    46
        Male
    82

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    MACI
    Reporting group description
    		 autologous cultured chondrocytes on porcine collagen membrane implant received in previous MACI00206 study

    Reporting group title
    Microfracture
    Reporting group description
    		 Arthroscopic Microfracture treatment received in the previous MACI00206 study
    Reporting group title
    MACI
    Reporting group description
    		 autologous cultured chondrocytes on porcine collagen membrane: Implantation

    Reporting group title
    Microfracture
    Reporting group description
    		 Microfracture: Arthroscopic Microfracture received in the parent study (MACI00206)

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety Analysis

    Primary: Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain Scores

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain Scores
    End point description
    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 for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores are pre-specified co-primary end points
    End point type
    Primary
    End point timeframe
    MACI00206 Baseline to Week 156
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    57
    Units: Change of Pain Scores
        arithmetic mean (full range (min-max))
    42.14 (-36.1 to 83.3)
    35.77 (-2.8 to 83.3)
    Statistical analysis title
    		 MANCOVA
    Statistical analysis description
    At Week 156 (3 years, co-primary endpoint), the improvement in the MACI group compared with microfracture was analyzed using the MANCOVA model.
    Comparison groups
    MACI v Microfracture
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    Parameter type
    		 LS Means
    Point estimate
    6.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.79
         upper limit
    		 16.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.84
    Notes
    [1] - Descriptive analysis

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

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Function (Sports and Recreational Activities) Scores.
    End point description
    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 for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain and Function (Sports and Recreational Activities) Scores are pre-specified co-primary end points
    End point type
    Primary
    End point timeframe
    MACI00206 Baseline to Week 156
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    57
    Units: Change in function scores
        arithmetic mean (full range (min-max))
    45.63 (-20.0 to 95.0)
    36.95 (-23.8 to 100)
    Statistical analysis title
    		 MANCOVA
    Comparison groups
    Microfracture v MACI
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 LS Mean
    Point estimate
    10.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.23
         upper limit
    		 24.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.49

    Secondary: Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain Scores

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Pain Scores
    End point description
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    59
    Units: Change in pain scores
        arithmetic mean (full range (min-max))
    45.17 (0 to 83.3)
    38.42 (-11.1 to 88.9)
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline for the Participant's Knee Injury and Osteoarthritis Outcome (KOOS) Function (Sports and Recreational Activities) Scores.
    End point description
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    64
    59
    Units: Change in function scores
        arithmetic mean (full range (min-max))
    47.17 (-10.0 to 95.0)
    37.56 (-20.0 to 100)
    No statistical analyses for this end point

    Secondary: Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill

    		 Close Top of page
    End point title
    		 Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    55
    Units: Patient
    44
    39
    No statistical analyses for this end point

    Secondary: Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores

    		 Close Top of page
    End point title
    		 Proportion of Patients Who Achieve at Least a 10-point Improvement From MACI00206 Baseline in KOOS Pain and Function (Sports and Recreational Activities) Scores
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Up to week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    63
    Units: Patient
    51
    46
    No statistical analyses for this end point

    Secondary: The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures

    		 Close Top of page
    End point title
    		 The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures
    End point description
    Patients were considered as a treatment failure if all of the following 5 criteria were met: Patient's global assessment of their knee joint compared to Baseline was the same or worse Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse. Percent improvement from Baseline in KOOS Pain score was less than 10%. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion. 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.
    End point type
    Secondary
    End point timeframe
    Years 2 through 5 post treatment (MACI or microfracture)
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    63
    Units: Patient
    1
    1
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living) of KOOS

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living) of KOOS
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    59
    Units: Change in Activities of Daily Living Sco
        arithmetic mean (full range (min-max))
    42.82 (-8.8 to 82.4)
    35.86 (-20.6 to 89.7)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the Remaining 3 Subscales (Quality of Life) of KOOS

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the Remaining 3 Subscales (Quality of Life) of KOOS
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    59
    Units: Change in QoL Score
        arithmetic mean (full range (min-max))
    39.9 (-18.8 to 93.8)
    34.53 (-37.5 to 100)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the Remaining 3 Subscales (Other Symptoms) of KOOS

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the Remaining 3 Subscales (Other Symptoms) of KOOS
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    57
    Units: Change in Other Symptoms Score
        arithmetic mean (full range (min-max))
    32.53 (-7.1 to 78.6)
    28.45 (-14.3 to 89.3)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    64
    59
    Units: Change in IKDC Score
        arithmetic mean (full range (min-max))
    35.48 (-11.5 to 80.5)
    31.58 (-21.8 to 85.1)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System
    End point description
    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).
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    59
    Units: Change in MCKR score
        arithmetic mean (full range (min-max))
    3.55 (-1.0 to 8.0)
    2.71 (-3.0 to 8.0)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical Scores

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical Scores
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    55
    Units: Change in SF-12 physical score
        arithmetic mean (full range (min-max))
    1.52 (-1.6 to 4.0)
    1.28 (-1.3 to 3.8)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score
    End point description
    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’.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    58
    Units: Change in VAS scale
        arithmetic mean (full range (min-max))
    20.14 (-15.0 to 68.0)
    17.1 (-40.0 to 85.0)
    No statistical analyses for this end point

    Secondary: Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Mental Component Scores

    		 Close Top of page
    End point title
    		 Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Mental Component Scores
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    From MACI00206 Baseline to Week 260
    End point values
    		 MACI Microfracture
    Number of subjects analysed
    65
    55
    Units: Change in SF-12 Mental score
        arithmetic mean (full range (min-max))
    0.38 (-2.2 to 3.3)
    0.52 (-2.0 to 3.9)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Years 2 through 5 post treatment (MACI or microfracture)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    MACI
    Reporting group description
    		 Patients treated with MACI in the parent study (MACI00206) and consented to participate in the MACI00809 study

    Reporting group title
    Microfracture
    Reporting group description
    		 Treatment received in the parent study (MACI00206) and consented to participate in the MACI00809 study

    Serious adverse events
    		 MACI Microfracture
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 65 (24.62%)
    17 / 63 (26.98%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Salivary gland neoplasm
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Cartilage Injury
         subjects affected / exposed
    2 / 65 (3.08%)
    7 / 63 (11.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft delamination
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus Injury
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant failure
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic injury
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Varicose vein
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Retained placenta or membranes
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Treatment Failure
         subjects affected / exposed
    3 / 65 (4.62%)
    5 / 63 (7.94%)
         occurrences causally related to treatment / all
    3 / 3
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 65 (1.54%)
    2 / 63 (3.17%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Otosclerosis
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric haemorrhage
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric stenosis
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometriosis
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    3 / 65 (4.62%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 65 (1.54%)
    5 / 63 (7.94%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 65 (1.54%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament laxity
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone disorder
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint lock
         subjects affected / exposed
    0 / 65 (0.00%)
    2 / 63 (3.17%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loose body in joint
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MACI Microfracture
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    49 / 65 (75.38%)
    46 / 63 (73.02%)
    Injury, poisoning and procedural complications
    Procedural Pain
         subjects affected / exposed
    2 / 65 (3.08%)
    5 / 63 (7.94%)
         occurrences all number
    4
    5
    Ligament sprain
         subjects affected / exposed
    1 / 65 (1.54%)
    5 / 63 (7.94%)
         occurrences all number
    1
    6
    Cartilage Injury
         subjects affected / exposed
    3 / 65 (4.62%)
    5 / 63 (7.94%)
         occurrences all number
    3
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 65 (16.92%)
    13 / 63 (20.63%)
         occurrences all number
    25
    28
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    29 / 65 (44.62%)
    32 / 63 (50.79%)
         occurrences all number
    62
    61
    Tendonitis
         subjects affected / exposed
    4 / 65 (6.15%)
    1 / 63 (1.59%)
         occurrences all number
    4
    1
    Back Pain
         subjects affected / exposed
    3 / 65 (4.62%)
    4 / 63 (6.35%)
         occurrences all number
    5
    5
    Osteoarthritis
         subjects affected / exposed
    2 / 65 (3.08%)
    5 / 63 (7.94%)
         occurrences all number
    2
    6
    Joint Effusion
         subjects affected / exposed
    2 / 65 (3.08%)
    5 / 63 (7.94%)
         occurrences all number
    2
    5
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 65 (10.77%)
    2 / 63 (3.17%)
         occurrences all number
    20
    3
    Influenza
         subjects affected / exposed
    4 / 65 (6.15%)
    5 / 63 (7.94%)
         occurrences all number
    6
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 01:13:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA