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Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee (SUMMIT)

Primary Purpose

Articular Cartilage Defect

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
autologous cultured chondrocytes on porcine collagen membrane
Microfracture
Sponsored by
Vericel Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Articular Cartilage Defect focused on measuring Cartilage legions, symptomatic focal cartilage defects, microfracture, MACI, autologous chondrocyte

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement

Exclusion Criteria:

  • Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
  • Severe osteoarthritis of the knee
  • Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders
  • Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.

Sites / Locations

  • Urazova nemocnice v Brne
  • Fakultni Nemocnice Na Bulovce
  • Fakultni Nemocnice v Motole
  • Hopital d'instruction des armees Robert Picque
  • Centre Hospitalier Lyon Sud
  • Polyclinique Saint-Roch
  • Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet
  • Academisch Ziekenhuis Maastricht
  • St. Elisabeth Ziekenhuis
  • UMC Utrecht
  • St Olavs Hospital
  • Szpital Uniwersytecki
  • Regional Hospital of Traumatologic Surgery
  • Center for Sports Medicine CMS
  • Medical Academy Warsaw
  • Kungsbacka Hospital
  • Capio Artro Clinic AB
  • The South West London Elective Orthopaedic Centre (SWLEOC)
  • Nuffield Dept. of Orthopaedic Surgery, University of Oxford
  • Spire Cheshire Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

MACI

Microfracture

Arm Description

autologous cultured chondrocytes on porcine collagen membrane

Microfracture

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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
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: 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 autologous cultured chondrocyte implantation.
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).
Participants With Treatment-Emergent Adverse Events

Full Information

First Posted
July 17, 2008
Last Updated
May 10, 2021
Sponsor
Vericel Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00719576
Brief Title
Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee
Acronym
SUMMIT
Official Title
A Prospective, Randomized, Open-label, Parallel-group, Multi-center Study to Demonstrate the Superiority of MACI® Versus Arthroscopic Microfracture for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vericel Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Articular Cartilage Defect
Keywords
Cartilage legions, symptomatic focal cartilage defects, microfracture, MACI, autologous chondrocyte

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MACI
Arm Type
Experimental
Arm Description
autologous cultured chondrocytes on porcine collagen membrane
Arm Title
Microfracture
Arm Type
Active Comparator
Arm Description
Microfracture
Intervention Type
Biological
Intervention Name(s)
autologous cultured chondrocytes on porcine collagen membrane
Other Intervention Name(s)
MACI, matrix-applied characterized autologous cultured chondrocytes
Intervention Description
Implantation via mini-arthrotomy
Intervention Type
Procedure
Intervention Name(s)
Microfracture
Intervention Description
Microfracture performed by arthroscopic surgery
Primary Outcome Measure Information:
Title
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.
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.
Time Frame
Baseline and Week 104
Secondary Outcome Measure Information:
Title
Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104
Description
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.
Time Frame
Week 104
Title
Assessment of Defect Fill by Magnetic Resonance Imaging (MRI)
Description
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.
Time Frame
Week 104
Title
Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104.
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 Baseline
Time Frame
Week 104
Title
Treatment Failure
Description
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: 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 autologous cultured chondrocyte implantation.
Time Frame
Week 104
Title
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)
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).
Time Frame
Baseline and Week 104
Title
Participants With Treatment-Emergent Adverse Events
Time Frame
Week 104

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement Exclusion Criteria: Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin Severe osteoarthritis of the knee Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Urazova nemocnice v Brne
City
Brno
Country
Czechia
Facility Name
Fakultni Nemocnice Na Bulovce
City
Prague
Country
Czechia
Facility Name
Fakultni Nemocnice v Motole
City
Prague
Country
Czechia
Facility Name
Hopital d'instruction des armees Robert Picque
City
Bordeaux
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Lyon
Country
France
Facility Name
Polyclinique Saint-Roch
City
Montpellier
Country
France
Facility Name
Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet
City
Paris
Country
France
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
Country
Netherlands
Facility Name
St. Elisabeth Ziekenhuis
City
Tilburg
Country
Netherlands
Facility Name
UMC Utrecht
City
Utrecht
Country
Netherlands
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Facility Name
Szpital Uniwersytecki
City
Bydgoszcz
Country
Poland
Facility Name
Regional Hospital of Traumatologic Surgery
City
Piekary Slaskie
Country
Poland
Facility Name
Center for Sports Medicine CMS
City
Warsaw
Country
Poland
Facility Name
Medical Academy Warsaw
City
Warsaw
Country
Poland
Facility Name
Kungsbacka Hospital
City
Kungsbacka
Country
Sweden
Facility Name
Capio Artro Clinic AB
City
Stockholm
Country
Sweden
Facility Name
The South West London Elective Orthopaedic Centre (SWLEOC)
City
Epsom
Country
United Kingdom
Facility Name
Nuffield Dept. of Orthopaedic Surgery, University of Oxford
City
Oxford
Country
United Kingdom
Facility Name
Spire Cheshire Hospital
City
Warrington
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24714783
Citation
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.
Results Reference
result

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Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee

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