Prospective, Randomised, Open Label, Multicentre Phase II Clinical Trial to Investigate the Efficacy and Safety of the Treatment of Large Cartilage Knee Defects(4-10 cm²) With 3 Diff. Doses of the ACT Product co.Don Chondrosphere®
Overview
- Phase
- Phase 2
- Intervention
- co.don chondrosphere®
- Conditions
- Large Articular Cartilage Lesions of the Femoral
- Sponsor
- co.don AG
- Enrollment
- 75
- Locations
- 10
- Primary Endpoint
- Change of overall KOOS
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients, age: between 18 and 50 years
- •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)
- •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
- •Nearly intact surrounding chondral structure around the defect as well as corresponding joint area
- •Informed consent signed by patient
- •Patient understands strict rehabilitation protocol and follow-up programme and is willing to follow it.
- •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
- •Defects on both knees at the same time
- •Radiological signs of osteoarthritis
- •Any signs of knee instability
- •Valgus or varus malalignment (more than 5° over the mechanical axis)
- •Clinically relevant second cartilage lesion on the same knee
- •More than 50 % resection of a meniscus in the affected knee or incomplete meniscal rim
- •Rheumatoid arthritis, parainfectious or infectious arthritis, and condition after these diseases
- •Pregnancy and planned pregnancy (no MRI possible)
- •Obesity (Body Mass Index \>30)
- •Uncontrolled diabetes mellitus
Arms & Interventions
co.don chondrosphere®, 3-7 spheroids/cm2
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group A is 3-7 spheroids/cm2 defect
Intervention: co.don chondrosphere®
co.don chondrosphere®,10-30spheroids/cm2
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group B is 10-30 spheroids/cm2 defect
Intervention: co.don chondrosphere®
co.don chondrosphere®,40-70spheroids/cm2
co.don chondrosphere® are spheroids in suspension, developed from autologous chondrocytes. The dose in group C is 40-70 Spheroids/cm2 defect
Intervention: co.don chondrosphere®
Outcomes
Primary Outcomes
Change of overall KOOS
Time Frame: 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 Outcomes
- Assessment of MRIs by the MOCART-Score (MRI Score)(12, 24, 36, 48 and 60 months after transplantation)
- 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 ICRS Visual Histological Assessment Score(12 months after transplantation)
- Change of overall KOOS(24, 36, 48, 60 months after transplantation)
- Change of the 5 subscores of the KOOS(12, 24, 36 ,48, 60 months after transplantation)
- Assessment of cartilage repair using an Arthroscopy and take a biopsy(12 months after transplantation)
- Assessment of change of modified Lysholm Score(12, 24, 36, 48 and 60 months after transplantation)
- Frequency and type of adverse events(3,12, 24, 36, 48, 60 months after transplantation)
- Change of ICRS/IKDC(12, 24, 36, 48 and 60 months after transplantation)
- Measurement of blood pressure, pulse and laboratory parameters(3, 6, 12, 24, 36, 48, 60 months after transplantation)
- Days of absence from work (employment) and/or days of inability to follow usual activities(annual)