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Prospective Multicenter Randomized Controlled Trial of ChondroCelect® (in an Autologous Chondrocyte Transplantation Procedure) vs Microfracture in the Repair of Symptomatic Defects of the Knee
This study is ongoing, but not recruiting participants.
Sponsored by: TiGenix n.v.
Information provided by: TiGenix n.v.
ClinicalTrials.gov Identifier: NCT00414700
  Purpose

This is a phase III, multicenter, open-label, randomized controlled trial of ChondroCelect® (in an Autologous Chondrocyte Transplantation procedure) compared to the procedure of microfracture (MF) in the repair of symptomatic cartilage lesions of the knee. Eligible patients attended two screening visits and were booked for arthroscopy approximately 2 weeks later. At that time, patients were randomized to either ACT with ChondroCelect® (also called Characterized Chondrocyte Implantation, CCI) or to MF, a procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. Patients randomized to MF had the procedure performed at the time of their arthroscopy; those randomized to CCI had their cells harvested during the arthroscopy and then returned to the clinic approximately 4 weeks later for an open knee procedure, during which the CCI procedure was performed. Patients subsequently followed the same rehabilitation program and had follow-up assessments up to 12 months post-surgery. The 12-month visit was the end-of-study visit for the TIG/ACT/01/2000 protocol. Subject to satisfying the eligibility criteria, patients who had participated in the initial 12 month trial could enter the extension trial (TIG/ACT/01/2000 EXT). The 12-month visit for the initial study was the baseline visit for the extension study. During the extension study, patients had follow-up assessments up to 60 months post-surgery.


Condition Intervention Phase
Articular Cartilage Lesion of the Femoral Condyle
Drug: ChondroCelect
Procedure: Characterized Chondrocyte Implantation
Phase III

U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Prospective Multicenter Randomized Controlled Trial of ChondroCelect® (in an Autologous Chondrocyte Transplantation Procedure) vs Microfracture (as Procedure) in the Repair of Symptomatic Cartilaginous Defects of the Femoral Condyles of the Knee

Further study details as provided by TiGenix n.v.:

Primary Outcome Measures:
  • EFFICACY: Histomorphometric scoring Safranin-O + Collagen II staining
  • Overall Histology Assessment Score (ICRS II)
  • Knee Osteoarthritis Outcome Score
  • SAFETY: adverse events
  • physical examination
  • vital signs
  • 12-lead EKG
  • MRI and X-ray
  • haematology
  • virology
  • clinical chemistry

Secondary Outcome Measures:
  • area under the curve (AUC) Overall KOOS score (long-term)
  • mean scores of the remaining 13 subscales ICRS II at 12 months
  • MOCART scale at 12 months
  • ICRS visual score at 12 months
  • KOOS individual domain scores averaged over 12 and 18 months
  • VAS pain score over 12 and 18 months
  • ARS score averaged over 12 and 18 months
  • all parameters assessed at 24, 30, 36, 48, and 60 months

Estimated Enrollment: 112
Study Start Date: March 2002
Estimated Study Completion Date: December 2009
Detailed Description:

cf brief summary

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed patient informed consent
  • Symptomatic cartilage single lesion of the femoral condyle
  • Lesion on femoral condyle between 1 and 5 cm²
  • Agree to participate actively in a strict rehabilitation protocol and follow-up programme
  • Agree to only use paracetamol mono-or combination preparation (max 4g/d) and NSAIDS during the study and to discontinue this medication 2 weeks before the baseline visit and the follow-up visits. The use of paracetamol mono-preparation (max 4g/d) is allowed up to one week before the baseline visit and the follow-up visits.
  • Females of childbearing age should use a proven method to prevent pregnancy

Exclusion Criteria:

  • Participation in concurrent trials
  • Participation in previous trials within 3 months
  • Subjects with hepatitis, HIV or syphilis
  • Malignancy
  • Alcohol or drug (medication) abuse
  • Poor general health as judged by Investigator
  • Clinically relevant second cartilage lesion on the patella
  • Patellofemoral cartilage lesion
  • Osteochondritis Dissecans (OCD) : recent OCD (within 1 year before baseline), depth of lesion > 0.5cm, subchondral slerosis
  • Advanced osteoarthritis (OA) : radiographic atlas of OA grade 2-3
  • Known allergy to gentamicin or penicillins (or presence of multiple severe allergies)
  • Complex ligamentous instability of the knee
  • Meniscal transplant
  • Meniscal suture with meniscal arrows (ipsilateral)
  • Meniscus resection : if < 1 yr before baseline - lateral meniscus resection or medial meniscus resection of more than 50%. If > 1 yr before baseline - ipsilateral meniscus resection of more than 50%, controlateral meniscus resection of more than 50% if ipsilateral meniscus is not intact, combination of medial and lateral meniscus resection and one of both > 50%.
  • Varus or valgus malalignment of more than 5°
  • Mosaicplasty (OATS)
  • Microfracture performed less than 1 yr before baseline
  • Having received hyaluronic acid intra-articular injections in the affected knee within the last 6 months of baseline
  • Taking specific OA drugs such as chondroïtin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of the baseline visit
  • Corticosteroïd treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroïds within the last 2 weeks of baseline
  • Chronic use of anticoagulants
  • Uncontrolled diabetes
  • 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 neurologic disorder of the lower extremities
  • Any evidence of the following diseases in the target joint : septic arthritis, inflammatory joint disease, gout, recurrent episodes of pseudogout, Paget's disease of bone, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary osteochondromatosis, heritable disorders, collagen gene mutation
  • Current diagnosis of osteomyelitis
  • Liver enzymes (SGOT, SGPT, Alkaline Phosphatase) of more then two times the upper limit of normal or any other result that is clinically important according to the Investigator
  • CRP > 10 mg/l
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00414700

Locations
Belgium
University Hospitals Leuven, Department of Orthopedics
Leuven, Belgium, 3000
AZ St Lucas Brugge, Department of Orthopedics
Brugge, Belgium, 8310
A.Z. Sint Jozef, Department of Orthopedics
Malle, Belgium, 2390
AZ St. Elisabeth, Department of Orthopedics
Herentals, Belgium, 2200
Ghent University Hospital, Department of Orthopedics
Ghent, Belgium, 9000
AZ St. Jan Brugge, Department of Orthopedics
Brugge, Belgium, 8000
Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics
Brussels, Belgium, 1090
SPM Monica Antwerp
Deurne, Belgium, 2100
AZ Groeninge, Department of Orthopedics
Kortrijk, Belgium, 8500
Croatia
Department of Orthopedic Surgery, School of Medicine, University of Zagreb
Zagreb, Croatia, 10000
Germany
University Hospital Hannover, Department of Orthopedics
Hannover, Germany, 30625
Netherlands
University Medical Center Utrecht, Department of Orthopedics
Utrecht, Netherlands, 3584
Sponsors and Collaborators
TiGenix n.v.
Investigators
Principal Investigator: Daniël Saris, M.D., Ph.D. University Medical Center Utrecht, Department of Orthopedics, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Principal Investigator: Johan Vanlauwe, M.D. University Hospitals Leuven, Department of Orthopedics, Herestraat 49, 3000 Leuven, Weligerveld 1, 3212 Pellenberg, Belgium.
Study Chair: Nancy Veulemans, Ir., M.S. VP Clinical and Regulatory Affairs, 4C Partner for TiGenix n.v.
Study Chair: Ludo Haazen, M.D. Medical Advisor, Envision bvba for TiGenix n.v.
Study Director: Frank P Luyten, M.D., Ph.D. Division of Rheumatology, Department of Muskuloskeletal Sciences, University Hospitals, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium
  More Information

Publications:
Dell'Accio F, Vanlauwe J, Bellemans J, Neys J, De Bari C, Luyten FP. Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res. 2003 Jan;21(1):123-31. Erratum in: J Orthop Res. 2003 May;21(3):572.
Dell'Accio F, De Bari C, Luyten FP. Microenvironment and phenotypic stability specify tissue formation by human articular cartilage-derived cells in vivo. Exp Cell Res. 2003 Jul 1;287(1):16-27.
Dell'Accio F, Vanlauwe J, Bellemans J, Neys J, De Bari C, Luyten FP. Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res. 2003 Jan;21(1):123-31. Erratum in: J Orthop Res. 2003 May;21(3):572.
Dell'Accio F, De Bari C, Luyten FP. Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum. 2001 Jul;44(7):1608-19.
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994 Oct 6;331(14):889-95.
Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004 Mar;86-A(3):455-64.
Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med. 2006 Sep 21;355(12):1274-7. No abstract available.

Study ID Numbers: TIG/ACT/01/2000, TIGACT01
Study First Received: December 21, 2006
Last Updated: December 21, 2006
ClinicalTrials.gov Identifier: NCT00414700  
Health Authority: United States: Food and Drug Administration;   Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment;   France: Afssaps - French Health Products Safety Agency;   Netherlands: Dutch Health Care Inspectorate;   Germany: Paul-Ehrlich-Institut;   Croatia: Ministry of Health and Social Care

Keywords provided by TiGenix n.v.:
Cartilage
Articular
Femoral
Knee

ClinicalTrials.gov processed this record on January 16, 2009