RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee (TIGACT01)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
TiGenix n.v.
ClinicalTrials.gov Identifier:
NCT00414700
First received: December 21, 2006
Last updated: September 22, 2011
Last verified: September 2011
  Purpose

This is a phase III, multicenter, open-label, randomized controlled trial of ChondroCelect® in an Autologous Chondrocyte Implantation (ACI) 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 ACI with ChondroCelect® 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 ACI with ChondroCelect® 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 ACI procedure using ChondroCelect® 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. The 12-month visit for the initial study was the baseline visit for the extension study. During the extension study, patients have follow-up assessments up to 60 months post-surgery.


Condition Intervention Phase
Articular Cartilage Lesion of the Femoral Condyle
Drug: ChondroCelect implantation
Procedure: Microfracture
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective Multicenter Randomized Controlled Trial of ChondroCelect® (Via Autologous Chondrocyte Implantation) vs Microfracture (as Procedure) in the Repair of Symptomatic Cartilaginous Defects of the Femoral Condyles

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining [ Time Frame: 12 months post-surgery ] [ Designated as safety issue: No ]
    Histomorphometry on end point biopsies at 12 months post-surgery. Safranin-O (ratio 0-1)+ anti-Collagen II antibody (ratio 0-1) stain signal expressed as a ratio of the total cartilage surface area (Saf O + anti Coll II divided by total surface = ratio 0-2). Safranin-O stains proteoglycans and anti-Collagen II antibody reflects the presence of Collagen II.

  • Overall Histology Assessment on First Subscale of ICRS II Score [ Time Frame: 12 months post-surgery ] [ Designated as safety issue: No ]
    Overall histology assessment of cartilage repair, first subscale of International Cartilage Repair Society II (ICRS II) score by two blinded independant histopathologists on a visual analogue scale (VAS 0-100mm) from worst (0) to best (100)

  • Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) [ Time Frame: Average change from baseline in Overall KOOS at 12-18 months post-surgery ] [ Designated as safety issue: No ]
    Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains, Sports not included) at the average of 12-18 months (calculated by averaging change from baseline measurements at 12 and 18 months). Best score = 100; worst score = 0. The analysis was the average of the change from baseline at the 12 and 18 months timepoints.


Secondary Outcome Measures:
  • Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months [ Time Frame: Change from baseline in Overall KOOS at 36 months post-surgery ] [ Designated as safety issue: No ]
    Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains: Activities of Daily Living, Quality of Life, Symptoms and Stiffness Pain; Sports not included) at 36 months (change from baseline). Best = 100; worst = 0.

  • Number of Treatment Failures at 36 Months [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]

    Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 36 months.

    The index lesion is the lesion that was initially treated in the study.


  • Safety: Adverse Events [ Time Frame: continuous up to 60 months ] [ Designated as safety issue: Yes ]
    Side effects are recorded as the number of patients with adverse events. These events are coded according to the Medical Dictionary for Regulatory Affairs (MedDRA terms).


Enrollment: 118
Study Start Date: February 2002
Study Completion Date: January 2010
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ChondroCelect Drug: ChondroCelect implantation

10.000 cells/µl cell suspension for implantation (Autologous Chondrocyte Implantation). ChondroCelect consists of characterised autologous cartilage-forming cells expressing a specific marker profile.

The dose depends on the size of the lesion. Recommended dose is 0.8 to 1.0 million cells/cm².

Other Name: CCI
Active Comparator: Microfracture Procedure: Microfracture
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.
Other Name: subchondral drilling

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:

  • 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 Non-Steroidal Anti Inflammatory Drugs (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
  • 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
AZ St. Jan Brugge, Department of Orthopedics
Brugge, Belgium, 8000
AZ St Lucas Brugge, Department of Orthopedics
Brugge, Belgium, 8310
Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics
Brussels, Belgium, 1090
SPM Monica Antwerp
Deurne, Belgium, 2100
Ghent University Hospital, Department of Orthopedics
Ghent, Belgium, 9000
AZ St. Elisabeth, Department of Orthopedics
Herentals, Belgium, 2200
AZ Groeninge, Department of Orthopedics
Kortrijk, Belgium, 8500
University Hospitals Leuven, Department of Orthopedics
Leuven, Belgium, 3000
A.Z. Sint Jozef, Department of Orthopedics
Malle, Belgium, 2390
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 BF 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 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:

Responsible Party: TiGenix n.v.
ClinicalTrials.gov Identifier: NCT00414700     History of Changes
Other Study ID Numbers: TIG/ACT/01/2000&Extension, BB IND 12491 0007
Study First Received: December 21, 2006
Results First Received: May 6, 2009
Last Updated: September 22, 2011
Health Authority: United States: Food and Drug Administration
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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 April 15, 2014