Efficacy and Safety Study of co.Don Chondrosphere to Treat Cartilage Defects

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by co.don AG
Sponsor:
Information provided by (Responsible Party):
co.don AG
ClinicalTrials.gov Identifier:
NCT01222559
First received: October 15, 2010
Last updated: July 11, 2014
Last verified: February 2013
  Purpose

This is a prospective, phase III, multicenter, open label, randomised clinical trial of co.don chondrosphere®, a three-dimensional autologous chondrocyte transplantation product (ACT3D-CS)compared to the procedure of microfracture (MF)in the treatment of cartilage defects of knee joints.

After screening visit patients were booked for arthroscopy and at that time they were randomised to either ACT3D-CS with co.don chondrosphere® (Group A) or to MF(Group B), a marrow-stimulating method based on the penetration of the subchondral bone plate at the bottom of the cartilage defect. At the time of arthroscopy Patients of group B had their procedure of MF (treatment surgery) and patients of group A had their cells harvested from healthy cartilage. The cells are cultivated for 8-10 weeks in vitro to develope 3-dimensional spheroids , that are transplanted in an open knee procedure (treatment surgery)into the defect. Patients subsequently followed the same rehabilitation program and had post-surgery visits. After the 12-month-visit a interim analyses will be performed and the 24-month-visit is defined as final assessment. Then patients have follow-up assessments up to 60 months post-treatment-surgery.


Condition Intervention Phase
Articular Cartilage Lesion of the Femoral Condyle
Drug: co.don chondrosphere®
Procedure: Microfracture
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Randomised, Open Label, Multicentre Phase-III Clinical Trial to Compare the Efficacy and Safety of the Treatment With the Autologous Chondrocyte Transplantation Product co.Don Chondrosphere (ACT3D-CS) With Microfracture in Subjects With Cartilage Defects of the Knee With a Defect Size Between 1 an 4 cm2

Resource links provided by NLM:


Further study details as provided by co.don AG:

Primary Outcome Measures:
  • Change of overall KOOS [ Time Frame: 24 months after the end of the respective treatment ] [ Designated as safety issue: No ]
    Change of overall KOOS (Knee Injury and Osteoarthritis Outcome Score)from baseline (Day 0)to final assessment compared between ACT3D-CS (co.don chondrosphere) and MF (microfracture)


Secondary Outcome Measures:
  • Change of overall KOOS [ Time Frame: 12, 36, 48, 60 months after the end of the respective treatment ] [ Designated as safety issue: No ]
    Change of overall KOOS(Knee Injury and Osteoarthritis Outcome Score) from baseline (Day 0) to 12 months, 36, 48, 60 months after the end of the respective treatment,compared between ACT3D-CS and MF

  • Change of the 5 subscores of the KOOS [ Time Frame: 12, 24, 36, 48, 60 months after the end of the respective treatment ] [ Designated as safety issue: No ]
    Change of the 5 subscores of the KOOS (Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec), knee related Quality of life (QoL)) for both treatment groups compared between ACT3D-CS and MF

  • MOCART (MRI Score) [ Time Frame: 12, 24, 36, 48 and 60 months after transplantation or microfracture ] [ Designated as safety issue: No ]
    MOCART (MRI Score) 12, 24, 36, 48 and 60 months after transplantation or microfracture compared between ACT3D-CS and MF

  • Arthroscopy and biopsy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Arthroscopy and biopsy at 24 months after transplantation/ microfracture, assessment of cartilage repair after ACT3D and microfracture to be compared between ACT3D-CS and MF

  • ICRS Visual Histological Assessment Score [ Time Frame: 24 months after respective treatment ] [ Designated as safety issue: No ]
    ICRS Visual Histological Assessment Score at final assessment (24 months) compared between ACT3D-CS and MF

  • Bern Score and additional histological assessment scores [ Time Frame: 24 months after the respective treatment ] [ Designated as safety issue: No ]
    Bern Score and additional histological assessment scores at final assessment (24 months) compared between ACT3D-CS and MF

  • Change of ICRS/IKDC [ Time Frame: 12, 24, 36, 48 and 60 months after the end of the respective treatment ] [ Designated as safety issue: No ]
    Change of ICRS/IKDC from baseline (Day 0) to 12, 24, 36, 48 and 60 months after the end of the respective treatment, compared between ACT3D-CS and MF

  • Change of modified Lysholm Score [ Time Frame: 12, 24, 36, 48 and 60 months after the end of the respective treatment ] [ Designated as safety issue: No ]
    Change of modified Lysholm Score from baseline (Day 0) to 12, 24, 36, 48 and 60 months after the end of the respective treatment compared between ACT3D-CS and MF

  • Days of absence from work (employment) and/or days of inability to follow usual activities [ Time Frame: annual ] [ Designated as safety issue: No ]
    Days of absence from work (employment) and/or days of inability to follow usual activities during the last year or since the last visit, respectively, and time point when patient was back to work and/or to follow usual activities

  • Safety Parameters [ Time Frame: 3,12,24 months after respective treatment ] [ Designated as safety issue: Yes ]
    Frequence and type of adverse Events Vital signs Physical examination Concomitant pain medication Laboratory parameters


Estimated Enrollment: 150
Study Start Date: October 2010
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: co.don chondrosphere®
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.
Drug: co.don chondrosphere®
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.
Other Name: ACT3D-CS
Active Comparator: Micofracture
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.
Drug: co.don chondrosphere®
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose depends on the size of the defect, recommended dose is 10-70 spheroids/cm2 defect.
Other Name: ACT3D-CS
Procedure: Microfracture
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form new tissue.
Other Name: Subchondral drilling

Detailed Description:

see above

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients, age: between 18 and 50 years
  2. Defect: isolated ICRS grade III or IV single defect chondral lesions on femoral condyles
  3. Defect size: 1 to < 4 cm2 after debridement to healthy cartilage up to 6 mm in depth.Assessment with MRI at screening and per estimation during arthroscopy prior to randomization
  4. Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area
  5. Informed consent signed and dated by patient
  6. Patient understands the strict rehabilitation protocol and follow-up programme and is willing to follow it
  7. In case of pain, patient agrees to use only paracetamol mono- (max 4 g/day) or combination preparation and oral and/or topic NSAIDs during the trial and to discontinue the use of oral and/or topic NSAIDs and/or paracetamol combination preparation 1 week before each visit whereas the use of paracetamol monopreparation (max 4 g/day) is allowed. However, in the morning of the visit day, no pain medication is allowed. Other pain medications are allowed during surgical procedure and may be taken for a period not exceeding 4 weeks after surgery.

Exclusion Criteria:

  1. Defects on both knees at the same time
  2. Radiological signs of osteoarthritis
  3. Osteochondritis dissecans (OCD)
  4. Any signs of knee instability
  5. Valgus or varus malalignment (more than 5° over the mechanical axis)
  6. Clinically relevant second cartilage lesion on the same knee
  7. More than 50 % resection of a meniscus in the affected knee or incomplete meniscal rim
  8. Rheumatoid arthritis, parainfectious or infectious arthritis, and condition after these diseases
  9. Pregnancy and planned pregnancy (no MRI possible)
  10. Obesity (Body Mass Index >30)
  11. Uncontrolled diabetes mellitus
  12. Serious illness
  13. Poor general health as judged by physician
  14. Participation in concurrent clinical trials or previous trials within 3 months of screening
  15. Previous treatment with ACT in the affected knee
  16. Microfracture performed less than 1 year before screening in the affected knee
  17. Alcohol or drug (medication) abuse
  18. Meniscal transplant in the affected knee
  19. Meniscal suture (in the affected knee) three months prior to baseline
  20. Mosaicplasty (Osteoarticular Transplant System, OATS) in the affected knee
  21. Having received hyaluronic acid intra-articular injections in the affected knee within the last 3 months before baseline
  22. Taking specific osteoarthritis drugs such as chondroïtin sulfate, diacerein, nglucosamine,piascledine, capsaicin within 2 weeks before baseline
  23. Corticosteroid treatment by systemic or intraarticular route within the last month of baseline or intramuscular or oral corticosteroïds within the last 2 weeks before baseline
  24. Chronic use of anticoagulants
  25. Any concomitant painful or disabling disease of the spine, hips or lower limbs that would interfere with evaluation of the afflicted knee
  26. Any clinically significant or symptomatic vascular or neurological disorder of the lower extremities
  27. Any evidence of the following diseases in the affected knee: septic arthritis, inflammatory joint disease, recurrent episodes of pseudogout, Paget's disease of bone, ochronosis, acromegaly, haemochromatosis, Wilson's disease, primary osteochondromatosis, heritable disorders, collagen gene mutation
  28. Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1,-2) and/or hepatitis C virus (HCV) infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222559

Locations
Germany
Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie Recruiting
Freiburg, Baden-Würrtemberg, Germany, 79106
Contact: Philipp Niemeyer, OA PD Dr.    076127018710      
Principal Investigator: Phillipp Niemeyer, OA PD Dr.med.         
Viktoria Klinik Bochum Private Klinik für Orthopädie und Orthopädische Chirurgie Recruiting
Bochum, Nordrhein-Westfalen, Germany, 44787
Contact: Alexander Rosenthal, Ph.D.    +49 234 ext 9122558      
Principal Investigator: Alexander Rosenthal, Ph.D.         
Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie Recruiting
Eisenberg, Tühringen, Germany, 07607
Contact: Stefan Pietsch, Ph.D.    +49 36691 ext 81439      
Principal Investigator: Stefan Pietsch, Ph.D.         
DRK-Kliniken Westend Recruiting
Berlin, Germany, 14050
Contact: Thilo John, Ph.D.    +49(0)30-30354250      
Principal Investigator: Thilo John, Ph.D.         
Gelenk-und Wirbelsäulenzentrum Steglitz Recruiting
Berlin, Germany, 12163
Contact: Volker Laute, Ph.D.    +49(0)30-79742750      
Principal Investigator: Volker Laute, Ph.D.         
St. Vinzenz-Hospital Recruiting
Dinslaken, Germany, 46535
Contact: Wolfgang Zinser, Ph.D.    +49(0)206-4441032      
Principal Investigator: Wolfgang Zinser, Ph.D.         
Orthopädische Klinik der Medizinischen Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Christoph Becher, Dr. med.    +49(0)511-5354333548      
Principal Investigator: Christoph Becher, Dr.med.         
Lubinus Clinicum Kiel Recruiting
Kiel, Germany, 24106
Contact: Jakob Fay, Ph.D.    +49(0)431-388204      
Principal Investigator: Jakob Fay, Ph.D.         
DRK Krankenhaus Luckenwalde Recruiting
Luckenwalde, Germany, 14943
Contact: Thomas Kolombe, Ph.D.    +49(0)3371-699315      
Principal Investigator: Thomas Kolombe, Ph.D.         
Orthopädisch-Unfallchirurgisches Zentrum Recruiting
Mannheim, Germany, 68167
Contact: Stefan Fickert, Ph.D.    +49(0)621-3834560      
Principal Investigator: Stefan Fickert, Ph.D.         
Poland
Wojewódzki Szpital Chirurgii Urazowej Recruiting
Piekary Śląskie, Poland, 62
Contact: Wojciech Widuchowski, Ph.D.       sportmed@sportmed.com.pl   
Principal Investigator: Widuchowski Wojciech, Ph.D.         
Centrum Medycyny Sportowej Recruiting
Warszawa, Poland
Contact: Andrzej Komor, Ph.D.       andrzej.komor@szpitalse.pl   
Principal Investigator: Andrzej Komor, Ph.D.         
Sponsors and Collaborators
co.don AG
Investigators
Principal Investigator: Stefan Fickert, Ph.D. Universitätsmedizin Mannheim
  More Information

No publications provided

Responsible Party: co.don AG
ClinicalTrials.gov Identifier: NCT01222559     History of Changes
Other Study ID Numbers: cod16HS13, 2009-016466-82
Study First Received: October 15, 2010
Last Updated: July 11, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by co.don AG:
Cartilage defects
Knee joint
Femoral Condyle

ClinicalTrials.gov processed this record on July 20, 2014