Phase 3 N=118 Randomized Single-blind Treatment

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

Articular Cartilage Lesion of the Femoral Condyle

Bottom Line

View on ClinicalTrials.gov: NCT00414700 ↗

Enrolled (actual)

118

Serious AEs

19.6%

Results posted

Jan 2010

Primary outcome: Primary: Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining — 1.01; 0.75 Ratio — p=0.003

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: ChondroCelect implantation (Drug); Microfracture (Procedure)
Age: Adult · 18+ yrs
Sex: All
Sponsor: TiGenix n.v.
Primary completion: Jul 2006

Outcome Measures

Outcome	Result	p-value
PRIMARY Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining	1.01; 0.75	0.003 sig
PRIMARY Overall Histology Assessment on First Subscale of ICRS II Score	55.11; 44.20	0.010 sig
PRIMARY Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)	16.18; 14.37; 56.30; 59.53; 73.26; 73.10	—
SECONDARY Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months	21.25; 15.83; 56.30; 59.46; 78.46; 74.47	—
SECONDARY Number of Treatment Failures at 36 Months	2; 7	—
SECONDARY Safety: Adverse Events	51; 61	—

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.

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 - 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

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Data sourced from ClinicalTrials.gov (NCT00414700). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.