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

Articular Cartilage Defects Clinical Trial

— Extension  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01251588
• Other study ID #: MACI00809
• Secondary ID: 2009-016970-33
• Status: Completed
• Start date: December 2010
• Est. completion date: March 2015

Study information

• Verified date: May 2021
• Source: Vericel Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years
• Eligibility: Randomized and received study treatment (MACI or microfracture) in the SUMMIT study.

Related Conditions & MeSH terms

• Articular Cartilage Defects
• Cartilage Diseases

Intervention

Biological:
• autologous cultured chondrocytes on porcine collagen membrane
Implantation received in the previous MACI00206 study

Procedure:
• Microfracture
Arthroscopic Microfracture treatment received in the previous MACI00206 study

Locations

Country	Name	City	State
Czechia	Urazova nemocnice v Brne	Brno
Czechia	University Hospital Na Bulovce- Department of Orthopaedic Surgery Postgraduate Medical Institute	Praha 8
France	Polyclinique Saint-Roch	Montpellier Cedex 2
France	Clinique Maussins-Nollet	Paris
France	Hôpital d'instruction des Armées Robert Picqué	VILLENAVE d'ORNON cedex
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	St. Elisabeth Ziekenhuis	Tilburg
Netherlands	University Medical Centre of Utrecht, Department of Orthopaedics	Utrecht
Norway	St Olavs Hospital	Trondheim
Poland	Orthopaedic & Traumatology of Motor Organs, Independent Public Clinic Hospital	Bydgoszcz
Poland	Regional Centre of Knee Surgery & Arthroscopy, Regional Hospital of Traumatologic Surgery	Piekary Slaskie
Poland	Lekmed Medical Center	Warsow
Sweden	Kungsbacka Närsjukhus	Kungsbacka
United Kingdom	University of Oxford, Nuffield Dept. of Orthopaedic Surgery	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Vericel Corporation

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	MACI00206 Baseline to Week 156
Secondary	Change From MACI00206 Baseline for the Participant's 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.	MACI00206 Baseline and Week 260
Secondary	Magnetic Resonance Imaging (MRI) Assessments of Degree of Defect Fill	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.	Week 260
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	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.	Up to week 260
Secondary	The Proportion of Patients in Each Treatment Group Assessed as Treatment Failures	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.	Years 2 through 5 post treatment (MACI or microfracture)
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: 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.	Up to 260 weeks
Secondary	Change From MACI00206 Baseline in the Remaining 3 Subscales (Activities of Daily Living, Quality of Life, and Other Symptoms) of KOOS	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.	MACI00206 Baseline and Week 260
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	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.	MACI00206 Baseline and Week 260
Secondary	Change From MACI00206 Baseline in the Patient's Evaluation of Overall Knee Condition Using the Modified Cincinnati Knee Rating System	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).	MACI00206 Baseline and Week 260
Secondary	Change From MACI00206 Baseline in the 12-Item Short-Form Health Survey (SF-12) Physical and Mental Component Scores	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.	MACI00206 Baseline and Week 260
Secondary	Change From MACI00206 Baseline in the European Quality of Life 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Score	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'.	MACI00206 Baseline and Week 260
Secondary	Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)		Years 2 through 5 post treatment (MACI or microfracture)
Secondary	Number of Participants Reporting Serious Adverse Events (SAEs)		Years 2 through 5 post treatment (MACI or microfracture)
Secondary	Number of Participants Having Subsequent Surgical Procedures (SSPs) in Target Knee		Years 2 through 5 post treatment (MACI or microfracture)