Assessment of Efficacy and Safety of 3 Different Doses of co.Don Chondrosphere to Treat Large Cartilage Defects

Inclusion Criteria: 1. Male or female patients, age: between 18 and 50 years 2. Defect: isolated ICRS grade III or IV single defect on medial or lateral femoral condyle, trochlea, tibia and retropatellar defects, also OCD (in case of OCD: Bone grafting up to the level of the original bone lamella must be performed if bone loss exceeds 3 mm in depth) 3. Defect size: ≥ 4 to 10 cm2 after debridement to healthy cartilage; chondral lesions, including osteochondritis dissecans on femoral condyle, trochlea, tibia,retropatellar defects up to 6 mm in depth. Assessment with MRI at Screening and per estimation during arthroscopy prior to randomization 4. Nearly intact surrounding chondral structure around the defect as well as corresponding joint area 5. Informed consent signed by patient 6. Patient understands 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 mono-preparation (max 4 g/day) is allowed. However, in the morning of the visit day, no pain medication is allowed. However, in the morning of the visit day, no pain medication is allowed. Other pain medications are allowed during surgical operation 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. Any signs of knee instability 4. Valgus or varus malalignment (more than 5° over the mechanical axis) 5. Clinically relevant second cartilage lesion on the same knee 6. More than 50 % resection of a meniscus in the affected knee or incomplete meniscal rim 7. Rheumatoid arthritis, parainfectious or infectious arthritis, and condition after these diseases 8. Pregnancy and planned pregnancy (no MRI possible) 9. Obesity (Body Mass Index \>30) 10. Uncontrolled diabetes mellitus 11. Serious illness 12. Poor general health as judged by physician 13. Participation in concurrent clinical trials or previous trials within 3 months of screening 14. Previous treatment with ACT in the affected knee 15. Microfracture performed less than 1 year before screening in the affected knee 16. Alcohol or drug (medication) abuse 17. Meniscal transplant in the affected knee 18. Meniscal suture (in the affected knee) three months prior to baseline 19. Mosaicplasty (Osteoarticular Transplant System, OATS) in the affected knee 20. Having received hyaluronic acid intra-articular injections in the affected knee within the last 3 months of baseline 21. Taking specific osteoarthritis drugs such as chondroitin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of baseline 22. Corticosteroid treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroids within the last 2 weeks of baseline 23. Chronic use of anticoagulants 24. Any concomitant painful or disabling disease of the spine, hips or lower limbs that would interfere with evaluation of the afflicted knee 25. Any clinically significant or symptomatic vascular or neurological disorder of the lower extremities 26. 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 27. Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1, 2) and/or hepatitis C (HCV) infection