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

Study Overview
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Brief Summary
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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.

Detailed Description
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see above

Official Title
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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

Conditions
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Articular Cartilage Lesion of the Femoral Condyle

Intervention / Treatment
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* Drug: co.don chondrosphere®
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, age: between 18 and 50 years Defect: isolated ICRS grade III or IV single defect chondral lesions on femoral condyles 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 Nearly intact chondral structure surrounding the defect as well as an intact corresponding joint area Informed consent signed and dated by patient Patient understands the 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 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: Defects on both knees at the same time Radiological signs of osteoarthritis Osteochondritis dissecans (OCD) 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 Serious illness Poor general health as judged by physician Participation in concurrent clinical trials or previous trials within 3 months of screening Previous treatment with ACT in the affected knee Microfracture performed less than 1 year before screening in the affected knee Alcohol or drug (medication) abuse Meniscal transplant in the affected knee Meniscal suture (in the affected knee) three months prior to baseline Mosaicplasty (Osteoarticular Transplant System, OATS) in the affected knee Having received hyaluronic acid intra-articular injections in the affected knee within the last 3 months before baseline Taking specific osteoarthritis drugs such as chondroïtin sulfate, diacerein, nglucosamine,piascledine, capsaicin within 2 weeks before baseline 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 Chronic use of anticoagulants Any concomitant painful or disabling disease of the spine, hips or lower limbs that would interfere with evaluation of the afflicted knee Any clinically significant or symptomatic vascular or neurological disorder of the lower extremities 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 Current diagnosis of osteomyelitis, human immunodeficiency virus (HIV-1,-2) and/or hepatitis C virus (HCV) infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: co.don chondrosphere®<br>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®<br>* 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.<br>* Other names: ACT3D-CS;|
| Active Comparator: Micofracture<br>A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. | Drug: co.don chondrosphere®<br>* 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.<br>* Other names: ACT3D-CS;Procedure: Microfracture<br>* A procedure in which the subchondral bone is perforated to allow a bloodcloth to form new tissue.<br>* Other names: Subchondral drilling;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of overall KOOS | 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) | 24 months after the end of the respective treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of overall KOOS | 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 | 12, 36, 48, 60 months after the end of the respective treatment | 
| Change of the 5 subscores of the KOOS | 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 | 12, 24, 36, 48, 60 months after the end of the respective treatment | 
| MOCART (MRI Score) | MOCART (MRI Score) 12, 24, 36, 48 and 60 months after transplantation or microfracture compared between ACT3D-CS and MF | 12, 24, 36, 48 and 60 months after transplantation or microfracture | 
| Arthroscopy and biopsy | 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 | 24 months | 
| ICRS Visual Histological Assessment Score | ICRS Visual Histological Assessment Score at final assessment (24 months) compared between ACT3D-CS and MF | 24 months after respective treatment | 
| Bern Score and additional histological assessment scores | Bern Score and additional histological assessment scores at final assessment (24 months) compared between ACT3D-CS and MF | 24 months after the respective treatment | 
| Change of ICRS/IKDC | 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 | 12, 24, 36, 48 and 60 months after the end of the respective treatment | 
| Change of modified Lysholm Score | 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 | 12, 24, 36, 48 and 60 months after the end of the respective treatment | 
| Days of absence from work (employment) and/or days of inability to follow usual activities | 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 | annual | 
| Safety Parameters | Frequence and type of adverse Events Vital signs Physical examination Concomitant pain medication Laboratory parameters | 3,12,24 months after respective treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cartilage defects, Knee joint, Femoral Condyle