Clinical trial NCT01222559: Efficacy and Safety Study of co.Don Chondrosphere to Treat Cartilage Defects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Articular Cartilage Lesion of the Femoral Condyle
Keywords: Cartilage defects
Knee joint
Femoral Condyle
Lead sponsor: co.don AG
Sponsor class: INDUSTRY
First posted: 2010-10-18
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: see above

Eligibility criteria: 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

Primary outcomes:
measure: Change of overall KOOS
timeFrame: 24 months after the end of the respective treatment
Secondary outcomes:
measure: Change of overall KOOS
timeFrame: 12, 36, 48, 60 months after the end of the respective treatment
measure: Change of the 5 subscores of the KOOS
timeFrame: 12, 24, 36, 48, 60 months after the end of the respective treatment
measure: MOCART (MRI Score)
timeFrame: 12, 24, 36, 48 and 60 months after transplantation or microfracture
measure: Arthroscopy and biopsy
timeFrame: 24 months
measure: ICRS Visual Histological Assessment Score
timeFrame: 24 months after respective treatment
measure: Bern Score and additional histological assessment scores
timeFrame: 24 months after the respective treatment
measure: Change of ICRS/IKDC
timeFrame: 12, 24, 36, 48 and 60 months after the end of the respective treatment
measure: Change of modified Lysholm Score
timeFrame: 12, 24, 36, 48 and 60 months after the end of the respective treatment
measure: Days of absence from work (employment) and/or days of inability to follow usual activities
timeFrame: annual
measure: Safety Parameters
timeFrame: 3,12,24 months after respective treatment
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie
state: Baden-Würrtemberg
city: Eisenberg
country: Germany
facility: Waldkrankenhaus "Rudolf Elle" GmbH Klinik für Orthopädie und Unfallchirurgie
state: Tühringen
city: Berlin
country: Germany
facility: Gelenk-und Wirbelsäulenzentrum Steglitz
city: Berlin
country: Germany
facility: DRK-Kliniken Westend
city: Dinslaken
country: Germany
facility: St. Vinzenz-Hospital
city: Hannover
country: Germany
facility: Orthopädische Klinik der Medizinischen Hochschule Hannover
city: Kiel
country: Germany
facility: Lubinus Clinicum Kiel
city: Luckenwalde
country: Germany
facility: DRK Krankenhaus Luckenwalde
city: Mannheim
country: Germany
facility: Orthopädisch-Unfallchirurgisches Zentrum
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku
city: Piekary Śląskie
country: Poland
facility: Wojewódzki Szpital Chirurgii Urazowej
city: Warszawa
country: Poland
facility: Centrum Medycyny Sportowej
Study officials:
affiliation: Universitätsmedizin Mannheim
name: Stefan Fickert, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoburg A, Niemeyer P, Laute V, Zinser W, Becher C, Kolombe T, Fay J, Pietsch S, Kuzma T, Widuchowski W, Fickert S. Matrix-Associated Autologous Chondrocyte Implantation with Spheroid Technology Is Superior to Arthroscopic Microfracture at 36 Months Regarding Activities of Daily Living and Sporting Activities after Treatment. Cartilage. 2021 Dec;13(1_suppl):437S-448S. doi: 10.1177/1947603519897290. Epub 2020 Jan 1.
citation: Niemeyer P, Laute V, Zinser W, Becher C, Kolombe T, Fay J, Pietsch S, Kuzma T, Widuchowski W, Fickert S. A Prospective, Randomized, Open-Label, Multicenter, Phase III Noninferiority Trial to Compare the Clinical Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroid Technology Versus Arthroscopic Microfracture for Cartilage Defects of the Knee. Orthop J Sports Med. 2019 Jul 10;7(7):2325967119854442. doi: 10.1177/2325967119854442. eCollection 2019 Jul.