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| ID | Type | Description | Link |
|---|---|---|---|
| 2006-004817-16 | EudraCT Number |
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The objective of this trial is to demonstrate superior efficacy and safety of MACI compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years) with symptomatic articular cartilage defects of the knee.
This is a prospective, randomized, open-label, parallel-group, multicenter study designed to investigate the outcome of MACI implant versus arthroscopic microfracture in the treatment of articular cartilage defects in the knee in patients between ages of 18 and 55 years.
All patients who meet the eligibility criteria and are considered suitable for inclusion will have a cartilage biopsy taken prior to randomization to study treatment. Eligible patients will then be randomized during the index arthroscopy procedure to receive either MACI implant or microfracture treatment.
Patients randomized to treatment with MACI implant will return within approximately 4 to 8 weeks of the index arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients randomized to microfracture will undergo the procedure during the index arthroscopy.
Patients will be assessed post-arthroscopy and post-arthrotomy at intervals during 2 years follow-up. Evaluations include adverse events, functional and pain outcomes, arthroscopic and histologic evaluation and magnetic resonance imaging (MRI).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MACI | Experimental | autologous cultured chondrocytes on porcine collagen membrane |
|
| Microfracture | Active Comparator | Microfracture |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| autologous cultured chondrocytes on porcine collagen membrane | Biological | Implantation via mini-arthrotomy |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (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. | Baseline and Week 104 |
| Measure | Description | Time Frame |
|---|---|---|
| Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104 | The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint. Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Genzyme, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Urazova nemocnice v Brne | Brno | Czechia | ||||
| Fakultni Nemocnice Na Bulovce |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24714783 | Result | Saris D, Price A, Widuchowski W, Bertrand-Marchand M, Caron J, Drogset JO, Emans P, Podskubka A, Tsuchida A, Kili S, Levine D, Brittberg M; SUMMIT study group. Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospective Randomized Trial. Am J Sports Med. 2014 Jun;42(6):1384-94. doi: 10.1177/0363546514528093. Epub 2014 Apr 8. |
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| ID | Title | Description |
|---|---|---|
| FG000 | MACI | autologous cultured chondrocytes on porcine collagen membrane |
| FG001 | Microfracture | Microfracture Microfracture: Microfracture |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Microfracture | Procedure | Microfracture performed by arthroscopic surgery |
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| Week 104 |
| Assessment of Defect Fill by Magnetic Resonance Imaging (MRI) | Number of participants with MRI degree of defect fill > 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment. Appropriate MRI sequences were used to image cartilage repair tissue. | Week 104 |
| Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104. | 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 Baseline | Week 104 |
| Treatment Failure | The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported. Patients were considered as a treatment failure if all of the following 5 criteria were met:
| Week 104 |
| Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms) | 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). | Baseline and Week 104 |
| Participants With Treatment-Emergent Adverse Events | Week 104 |
| Prague |
| Czechia |
| Fakultni Nemocnice v Motole | Prague | Czechia |
| Hopital d'instruction des armees Robert Picque | Bordeaux | France |
| Centre Hospitalier Lyon Sud | Lyon | France |
| Polyclinique Saint-Roch | Montpellier | France |
| Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet | Paris | France |
| Academisch Ziekenhuis Maastricht | Maastricht | Netherlands |
| St. Elisabeth Ziekenhuis | Tilburg | Netherlands |
| UMC Utrecht | Utrecht | Netherlands |
| St Olavs Hospital | Trondheim | Norway |
| Szpital Uniwersytecki | Bydgoszcz | Poland |
| Regional Hospital of Traumatologic Surgery | Piekary Śląskie | Poland |
| Center for Sports Medicine CMS | Warsaw | Poland |
| Medical Academy Warsaw | Warsaw | Poland |
| Kungsbacka Hospital | Kungsbacka | Sweden |
| Capio Artro Clinic AB | Stockholm | Sweden |
| The South West London Elective Orthopaedic Centre (SWLEOC) | Epsom | United Kingdom |
| Nuffield Dept. of Orthopaedic Surgery, University of Oxford | Oxford | United Kingdom |
| Spire Cheshire Hospital | Warrington | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | MACI | autologous cultured chondrocytes on porcine collagen membrane |
| BG001 | Microfracture | Microfracture |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (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. | All randomized patients | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 104 |
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| Secondary | Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104 | The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint. Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage. | includes all subjects with histology follow-up data | Posted | Least Squares Mean | Full Range | units on a scale | Week 104 |
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| Secondary | Assessment of Defect Fill by Magnetic Resonance Imaging (MRI) | Number of participants with MRI degree of defect fill > 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment. Appropriate MRI sequences were used to image cartilage repair tissue. | Number of participants with MRI data at Week 104 | Posted | Count of Participants | Participants | Week 104 |
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| Secondary | Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104. | 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 Baseline | Posted | Count of Participants | Participants | Week 104 |
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| Secondary | Treatment Failure | The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported. Patients were considered as a treatment failure if all of the following 5 criteria were met:
| Posted | Count of Participants | Participants | Week 104 |
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| Secondary | Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms) | 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). | Posted | Mean | Standard Deviation | units on a scale | Baseline and Week 104 |
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| Secondary | Participants With Treatment-Emergent Adverse Events | Posted | Count of Participants | Participants | Week 104 |
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Week 104
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MACI | autologous cultured chondrocytes on porcine collagen membrane | 11 | 72 | 55 | 72 | ||
| EG001 | Microfracture | Microfracture | 19 | 72 | 58 | 72 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
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| Impaired healing | General disorders | MedDRA (14.1) | Systematic Assessment |
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| Treatment failure | General disorders | MedDRA (14.1) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
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| Wound infection staphylococcal | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
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| Cartilage injury | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Graft delamination | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Meniscus lesion | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Transplant failure | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Traumatic fracture | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Joint lock | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Knee deformity | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Loose body in joint | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Osteochondrosis | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Patellofemoral pain syndrome | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
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| Multiple sclerosis | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA (14.1) | Systematic Assessment |
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| Urinary retention | Renal and urinary disorders | MedDRA (14.1) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
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| Thrombosis | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Ligament sprain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
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Because clinical trials are conducted under widely varying conditions, adverse event rates observed in clinical trials cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ann Remmers, Senior Director, Clinical Science | Vericel Corporation | 734-428-4526 | aremmers@vcel.com |
| ID | Term |
|---|---|
| D015775 | Fractures, Stress |
| ID | Term |
|---|---|
| D050723 | Fractures, Bone |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D054544 | Arthroplasty, Subchondral |
| ID | Term |
|---|---|
| D001178 | Arthroplasty |
| D019637 | Orthopedic Procedures |
| D013514 | Surgical Procedures, Operative |
| D019651 | Plastic Surgery Procedures |
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| Netherlands |
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| Sweden |
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| Norway |
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| Poland |
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| United Kingdom |
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| France |
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