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

NCT ID: NCT00414700

Last Updated: 2011-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2010-01-31

Brief Summary

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.

Detailed Description

see above

Conditions

Articular Cartilage Lesion of the Femoral Condyle

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ChondroCelect

Group Type: EXPERIMENTAL

ChondroCelect implantation

Intervention Type: DRUG

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.

Microfracture

Group Type: ACTIVE_COMPARATOR

Microfracture

Intervention Type: PROCEDURE

A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.

Interventions

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.

Intervention Type: DRUG

Microfracture

A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.

Intervention Type: PROCEDURE

Other Intervention Names

CCI; subchondral drilling

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TiGenix n.v.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniël BF Saris, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Utrecht, Department of Orthopedics, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Johan Vanlauwe, M.D.

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Leuven, Department of Orthopedics, Herestraat 49, 3000 Leuven, Weligerveld 1, 3212 Pellenberg, Belgium.

Frank P Luyten, M.D., Ph.D.

Role: STUDY_DIRECTOR

Division of Rheumatology, Department of Muskuloskeletal Sciences, University Hospitals, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium

Locations

AZ St. Jan Brugge, Department of Orthopedics

Bruges, , Belgium

AZ St Lucas Brugge, Department of Orthopedics

Bruges, , Belgium

Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics

Brussels, , Belgium

SPM Monica Antwerp

Deurne, , Belgium

Ghent University Hospital, Department of Orthopedics

Ghent, , Belgium

AZ St. Elisabeth, Department of Orthopedics

Herentals, , Belgium

AZ Groeninge, Department of Orthopedics

Kortrijk, , Belgium

University Hospitals Leuven, Department of Orthopedics

Leuven, , Belgium

A.Z. Sint Jozef, Department of Orthopedics

Malle, , Belgium

Department of Orthopedic Surgery, School of Medicine, University of Zagreb

Zagreb, , Croatia

University Hospital Hannover, Department of Orthopedics

Hanover, , Germany

University Medical Center Utrecht, Department of Orthopedics

Utrecht, , Netherlands

Countries

Belgium; Croatia; Germany; Netherlands

References

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. doi: 10.1016/S0736-0266(02)00090-6.

Reference Type: BACKGROUND

PMID: 12507589 (View on PubMed)

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. doi: 10.1016/s0014-4827(03)00036-3.

Reference Type: BACKGROUND

PMID: 12799178 (View on PubMed)

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. doi: 10.1002/1529-0131(200107)44:73.0.CO;2-T.

Reference Type: BACKGROUND

PMID: 11465712 (View on PubMed)

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. doi: 10.1056/NEJM199410063311401.

Reference Type: BACKGROUND

PMID: 8078550 (View on PubMed)

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(3):455-64. doi: 10.2106/00004623-200403000-00001.

Reference Type: BACKGROUND

PMID: 14996869 (View on PubMed)

Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med. 2006 Sep 21;355(12):1274-7. doi: 10.1056/NEJMe068172. No abstract available.

Reference Type: BACKGROUND

PMID: 16990391 (View on PubMed)

Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008 Feb;36(2):235-46. doi: 10.1177/0363546507311095.

Reference Type: RESULT

PMID: 18202295 (View on PubMed)

Saris DB, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP; TIG/ACT/01/2000&EXT Study Group. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med. 2009 Nov;37 Suppl 1:10S-19S. doi: 10.1177/0363546509350694. Epub 2009 Oct 21.

Reference Type: RESULT

PMID: 19846694 (View on PubMed)

Other Identifiers

BB IND 12491 0007

Identifier Type: OTHER

Identifier Source: secondary_id

TIG/ACT/01/2000&Extension

Identifier Type: -

Identifier Source: org_study_id