IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.

Lead Sponsor: UMC Utrecht

Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure which is limited by the number of chondrocytes obtained by biopsy and the dedifferentiation resulting from the expansion phase. Therefore, there is a need for improvement. A new cartilage repair technique should aim at decreasing surgical trauma, lowering complexity, improving logistics and cost-effectiveness while retaining or improving clinical outcome. Direct contact between mesenchymal stromal cells (MSCs) and dedifferentiated articular chondrocytes in vitro showed improvement of the chondrogenic phenotype of dedifferentiated articular chondrocytes. In addition, preserving the pericellular matrix of chondrocytes improves cartilage formation. These chondrons (chondrocytes with their pericellular matrix) have shown improved cartilage formation when combined with allogeneic MSCs in extensive preclinical studies. The cells are mixed with fibrin cell carrier and applied to the cartilage lesion within one surgical procedure. This will reduce patient morbidity and improve patient care through immediate transplantation of a potent cell-based cartilage product. This is a phase I/II prospective monocenter study to evaluate the safety and feasibility of the IMPACT for treatment of focal articular cartilage lesions of the knee.

• Foreign-Body Reaction
• Inflammation
• Effusion (L) Knee
• Knee Pain Swelling

Intervention Type: Other

Intervention Name: Cartilage repair surgery

Description: Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs

Arm Group Label: Cartilage repair surgery

Criteria:

Inclusion Criteria: - Age >18 and <45 years old - Symptomatic isolated full-thickness articular cartilage lesion on the femoral condyle or trochlea. - Size 2 - 8 cm2 - Intact anterior cruciate ligament Exclusion Criteria: - (History of) osteoarthritis, defined as Kellgren-Lawrence grade >3 as determined from appropriate X-ray. - Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis) - (History of) Septic arthritis. - Malalignment requiring an osteotomy. - (History of) total menisectomy in the target knee joint. - Any surgery in the knee joint 6 months prior to study inclusion. - Risk groups for MRI scanning due to the magnetic field like patients with pacemakers, nerve stimulators, metal particles, stents, clips or implants, (possible) pregnancy or breast feeding. - Patients with severe anxiety for MRI scans and/or needles

Gender: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Healthy Volunteers: No

Netherlands

June 2018

Type: Principal Investigator

Investigator Affiliation: UMC Utrecht

Investigator Full Name: D.B.F. Saris

Investigator Title: MD, PhD, Orthopaedic surgeon

• IMPACT
• Chondrons
• Mesenchymal stem cells
• Allogeneic MSCs
• single-stage
• Cartilage repair
• Safety
• Efficacy

• Inflammation
• Foreign-Body Reaction
• Foreign Bodies

Label: Cartilage repair surgery

Type: Experimental

Description: Single-stage cartilage repair surgery using autologous chondrons (10-20%) and allogeneic MSCs (80-90%) in a fibrin glue carrier with a dosage of two million cells/ cm2 applied once during a surgical procedure.

Allocation: N/A

Intervention Model: Single Group Assignment

Intervention Model Description: First in man surgery: autologous chondrons are mixed with allogeneic MSCs and implanted in a fibrin glue carrier in a one-stage surgical procedure.

Primary Purpose: Treatment

Masking: None (Open Label)