Assessment of Efficacy and Safety of 3 Different Doses of co.Don Chondrosphere to Treat Large Cartilage Defects

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
co.don AG
ClinicalTrials.gov Identifier:
NCT01225575
First received: October 18, 2010
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Large Articular Cartilage Lesions of the Femoral
Condyle, Trochlea, Tibia or Retropatellar
Drug: co.don chondrosphere®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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®

Resource links provided by NLM:


Further study details as provided by co.don AG:

Primary Outcome Measures:
  • Change of overall KOOS [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change of overall KOOS [ Time Frame: 24, 36, 48, 60 months after transplantation ] [ Designated as safety issue: No ]
    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

  • Change of the 5 subscores of the KOOS [ Time Frame: 12, 24, 36 ,48, 60 months after transplantation ] [ Designated as safety issue: No ]
    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) [ Time Frame: 12, 24, 36, 48 and 60 months after transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]
    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 ICRS/IKDC [ Time Frame: 12, 24, 36, 48 and 60 months after transplantation ] [ Designated as safety issue: No ]
    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

  • Assessment of change of modified Lysholm Score [ Time Frame: 12, 24, 36, 48 and 60 months after transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: annual ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3,12, 24, 36, 48, 60 months after transplantation ] [ Designated as safety issue: Yes ]
    Frequency and type of adverse events

  • Measurement of blood pressure, pulse and laboratory parameters [ Time Frame: 3, 6, 12, 24, 36, 48, 60 months after transplantation ] [ Designated as safety issue: Yes ]
    Measurement of the vital signs and physical examination, laboratory parameters at 3 and 12 months after transplantation.


Estimated Enrollment: 75
Study Start Date: October 2010
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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

Drug: co.don chondrosphere®

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

Other Name: ACT3D-CS
Active Comparator: 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

Drug: co.don chondrosphere®

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

Other Name: ACT3D-CS
Active Comparator: 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

Drug: co.don chondrosphere®

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

Other Name: ACT3D-CS

Detailed Description:

see above

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01225575

Locations
Germany
Universitätsklinikum der Albert-Ludwig-Universität Freiburg, Department Othopädie und Traumatologie
Freiburg, Baden-Würrtemberg, Germany, 79106
ATOS Klinikum Heidelberg, Zentrum für Knie- und Fußchirurgie
Heidelberg, Baden-Würrtemberg, Germany, 69115
DRK-Kliniken Westend
Berlin, Germany, 14050
Gelenk-und Wirbelsäulenzentrum Steglitz
Berlin, Germany, 12163
Viktoria Klinik Bochum Private Fachklinik für Orthopädie und Orthopädische Chirurgie Sportklinik Viktoria
Bochum, Germany, 44787
St. Vinzenz-Hospital
Dinslaken, Germany, 46535
Orthopädische Klinik der Medizinischen Hochschule Hannover
Hannover, Germany, 30625
Lubinus Clinicum Kiel
Kiel, Germany, 24106
DRK Krankenhaus Luckenwalde
Luckenwalde, Germany, 14943
Orthopädisch-Unfallchirurgisches Zentrum
Mannheim, Germany, 68167
Orthopädiezentrum München Ost
München, Germany, 85567
Sponsors and Collaborators
co.don AG
Investigators
Principal Investigator: Stefan Fickert, Ph.D. Universitätsmedizin Mannheim
  More Information

No publications provided

Responsible Party: co.don AG
ClinicalTrials.gov Identifier: NCT01225575     History of Changes
Other Study ID Numbers: cod 16HS14, 2009-016816-20
Study First Received: October 18, 2010
Last Updated: February 14, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by co.don AG:
large cartilage defects
knee joint
femoral condyle, tibia, trochlear, retropatellar

ClinicalTrials.gov processed this record on April 22, 2014