Clinical trial NCT01225575: Assessment of Efficacy and Safety of 3 Different Doses of co.Don Chondrosphere to Treat Large Cartilage Defects
Official title: 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®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Large Articular Cartilage Lesions of the Femoral
Condyle, Trochlea, Tibia or Retropatellar
Keywords: large cartilage defects
knee joint
femoral condyle, tibia, trochlear, retropatellar
Lead sponsor: co.don AG
Sponsor class: INDUSTRY
First posted: 2010-10-21
Enrollment: 75
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, 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

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 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

Primary outcomes:
measure: Change of overall KOOS
timeFrame: 12 months after transplantation
Secondary outcomes:
measure: Change of overall KOOS
timeFrame: 24, 36, 48, 60 months after transplantation
measure: Change of the 5 subscores of the KOOS
timeFrame: 12, 24, 36 ,48, 60 months after transplantation
measure: Assessment of MRIs by the MOCART-Score (MRI Score)
timeFrame: 12, 24, 36, 48 and 60 months after transplantation
measure: Assessment of cartilage repair using an Arthroscopy and take a biopsy
timeFrame: 12 months after transplantation
measure: Assessment of the histology from the biopsy by ICRS Visual Histological Assessment Score
timeFrame: 12 months after transplantation
measure: Assessment of the histology from the biopsy by the Bern Score and additional histological scores
timeFrame: 12 months after transplantation
measure: Change of ICRS/IKDC
timeFrame: 12, 24, 36, 48 and 60 months after transplantation
measure: Assessment of change of modified Lysholm Score
timeFrame: 12, 24, 36, 48 and 60 months after transplantation
measure: Days of absence from work (employment) and/or days of inability to follow usual activities
timeFrame: annual
measure: Frequency and type of adverse events
timeFrame: 3,12, 24, 36, 48, 60 months after transplantation
measure: Measurement of blood pressure, pulse and laboratory parameters
timeFrame: 3, 6, 12, 24, 36, 48, 60 months after transplantation
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie
state: Baden-Würrtemberg
city: Heidelberg
country: Germany
facility: ATOS Klinikum Heidelberg, Zentrum für Knie- und Fußchirurgie
state: Baden-Würrtemberg
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: München
country: Germany
facility: Orthopädiezentrum München Ost
Study officials:
affiliation: Universitätsmedizin Mannheim
name: Stefan Fickert, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoburg A, Niemeyer P, Laute V, Zinser W, John T, Becher C, Izadpanah K, Diehl P, Kolombe T, Fay J, Siebold R, Fickert S. Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial. Orthop J Sports Med. 2022 Jan 18;10(1):23259671211053380. doi: 10.1177/23259671211053380. eCollection 2022 Jan.
citation: Becher C, Laute V, Fickert S, Zinser W, Niemeyer P, John T, Diehl P, Kolombe T, Siebold R, Fay J. Safety of three different product doses in autologous chondrocyte implantation: results of a prospective, randomised, controlled trial. J Orthop Surg Res. 2017 May 12;12(1):71. doi: 10.1186/s13018-017-0570-7.
citation: Niemeyer P, Laute V, John T, Becher C, Diehl P, Kolombe T, Fay J, Siebold R, Niks M, Fickert S, Zinser W. The Effect of Cell Dose on the Early Magnetic Resonance Morphological Outcomes of Autologous Cell Implantation for Articular Cartilage Defects in the Knee: A Randomized Clinical Trial. Am J Sports Med. 2016 Aug;44(8):2005-14. doi: 10.1177/0363546516646092. Epub 2016 May 20.