Condyle, Trochlea, Tibia or Retropatellar, Large Articular Cartilage Lesions of the Femoral
Conditions
Keywords
large cartilage defects, knee joint, femoral condyle, tibia, trochlear, retropatellar
Brief summary
This is a prospective, randomised, open label, multicentre Phase II clinical trial to investigate the efficacy and safety of the treatment of large defects with 3 different doses of the autologous chondrocyte transplantation product co.don chondrosphere® (ACT3D-CS) in subjects with cartilage defects of the knee. After screening visit patients were booked for arthroscopy and had their cells harvesting from healthy cartilage. After the arthroscopy the patients were randomised in one of the three dose-groups. 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 of all dose groups subsequently followed the same rehabilitation program and had post-surgery visits. The 12-month-visit is defined as final assessment. Then patients have follow-up assessments up to 60 months.
Detailed description
see above
Interventions
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group A is 3-7 spheroids/cm2 defect, in group B 10-30 spheroids/cm2 defect and in group C 40-70 spheroids/cm2 defect
Sponsors
co.don AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of overall KOOS | 12 months after transplantation | Change of overall KOOS (Knee Injury and Osteoarthritis Outcome Score) from baseline (Day 0)to final assessment (FA)determined for each dosage group and between the dosage groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of the 5 subscores of the KOOS | 12, 24, 36 ,48, 60 months after transplantation | 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)) determined for each dosage group and between the dosage groups |
| Assessment of MRIs by the MOCART-Score (MRI Score) | 12, 24, 36, 48 and 60 months after transplantation | Assessment of MRIs by the MOCART-Score (MRI Score) at 12, 24, 36, 48 and 60 months after transplantation compared between the dosage groups |
| Assessment of cartilage repair using an Arthroscopy and take a biopsy | 12 months after transplantation | Arthroscopy and biopsy at 12 months after transplantation, assessment of cartilage repair after ACT3D to be compared for each dosage group and between the dosage groups |
| Assessment of the histology from the biopsy by ICRS Visual Histological Assessment Score | 12 months after transplantation | Assessment of the ICRS Visual Histological Assessment Score at final assessment (FA, 12 months) determined for each dosage group and compared between the dosage groups |
| Assessment of the histology from the biopsy by the Bern Score and additional histological scores | 12 months after transplantation | Assessment of the histology from the biopsy by the Bern Score and additional histological assessment scores at final assessment (12 months) determined for each dosage group and compared between the dosage groups |
| Change of overall KOOS | 24, 36, 48, 60 months after transplantation | Change of overall KOOS from baseline (Day 0) to 24,36, 48 and 60 months follow-up, FU) after transplantation determined for each dosage group and compared between the dosage groups |
| Assessment of change of modified Lysholm Score | 12, 24, 36, 48 and 60 months after transplantation | Change of modified Lysholm Score from baseline (Day 0) to 12, 24, 36, 48 and 60 months after transplantation determined for each dosage group and compared between the dosage the groups |
| Days of absence from work (employment) and/or days of inability to follow usual activities | annual | 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 |
| Frequency and type of adverse events | 3,12, 24, 36, 48, 60 months after transplantation | Frequency and type of adverse events |
| Measurement of blood pressure, pulse and laboratory parameters | 3, 6, 12, 24, 36, 48, 60 months after transplantation | Measurement of the vital signs and physical examination, laboratory parameters at 3 and 12 months after transplantation. |
| Change of ICRS/IKDC | 12, 24, 36, 48 and 60 months after transplantation | Change of ICRS/IKDC from baseline (Day 0) to 12, 24, 36, 48 and 60 months after transplantation determined for each dosage group and compared between the dosage groups |
Countries
Germany
Outcome results
None listed