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

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

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.

see above

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