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

NCT00414700 | Completed Phase 3 Results

• 2 other identifiers: TIG/ACT/01/2000&ExtensionBB IND 12491 0007
• Study Type: interventional
• Target: 118
• Locations: 4 countries
• Sites: 12

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.

Conditions

Articular Cartilage Lesion of the Femoral Condyle

Keywords

Cartilage; Articular; Femoral; Knee

Outcome Measures

Primary Outcomes (3)

• Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining

  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.

  12 months post-surgery

• Overall Histology Assessment on First Subscale of ICRS II Score

  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)

  12 months post-surgery

• Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)

  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.

  Average change from baseline in Overall KOOS at 12-18 months post-surgery

Secondary Outcomes (3)

• Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months

  Change from baseline in Overall KOOS at 36 months post-surgery

• Number of Treatment Failures at 36 Months

  Continuous

• Safety: Adverse Events

  continuous up to 60 months

Study Arms (2)

ChondroCelect

EXPERIMENTAL

Drug: ChondroCelect implantation

Microfracture

ACTIVE COMPARATOR

Procedure: Microfracture

Interventions

ChondroCelect implantation 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.

Also known as: CCI

ChondroCelect

Microfracture PROCEDURE

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

Also known as: subchondral drilling

Microfracture

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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%.

Sponsors & Collaborators

• TiGenix n.v.: lead

Study Sites (12)

AZ St. Jan Brugge, Department of Orthopedics

Bruges, 8000, Belgium

Location

AZ St Lucas Brugge, Department of Orthopedics

Bruges, 8310, Belgium

Location

Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics

Brussels, 1090, Belgium

Location

SPM Monica Antwerp

Deurne, 2100, Belgium

Location

Ghent University Hospital, Department of Orthopedics

Ghent, 9000, Belgium

Location

AZ St. Elisabeth, Department of Orthopedics

Herentals, 2200, Belgium

Location

AZ Groeninge, Department of Orthopedics

Kortrijk, 8500, Belgium

Location

University Hospitals Leuven, Department of Orthopedics

Leuven, 3000, Belgium

Location

A.Z. Sint Jozef, Department of Orthopedics

Malle, 2390, Belgium

Location

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

Zagreb, 10000, Croatia

Location

University Hospital Hannover, Department of Orthopedics

Hanover, 30625, Germany

Location

University Medical Center Utrecht, Department of Orthopedics

Utrecht, 3584, Netherlands

Location

Related Publications (8)

• 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.

  PMID: 12507589 BACKGROUND

• 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.

  PMID: 12799178 BACKGROUND

• 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.

  PMID: 11465712 BACKGROUND

• 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.

  PMID: 8078550 BACKGROUND

• 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.

  PMID: 14996869 BACKGROUND

• 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.

  PMID: 16990391 BACKGROUND

• 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.

  PMID: 18202295 RESULT

• 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.

  PMID: 19846694 RESULT

MeSH Terms

Interventions

Arthroplasty, Subchondral

Intervention Hierarchy (Ancestors)

Arthroplasty; Orthopedic Procedures; Surgical Procedures, Operative; Plastic Surgery Procedures

Results Point of Contact

• Title: Nel Van Lommel, MSc, Manager Clinical Operations Europe, TiGenix n.v.
• Organization: TiGenix n.v.

nel.vanlommel@tigenix.com

+3216396060

Study Officials

• 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.

  PRINCIPAL INVESTIGATOR

• Frank P Luyten, M.D., Ph.D.

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2006
• First Posted: December 22, 2006
• Study Start: February 1, 2002
• Primary Completion: July 1, 2006
• Study Completion: January 1, 2010
• Last Updated: September 26, 2011
• Results First Posted: January 18, 2010

Record last verified: 2011-09

Locations

DE (1); BE (9); NL (1); CR (1)