Prospective monocenter study on clinical outcomes and safety of Instant MSC Product accompanying Autologous Chondron Transplantation (IMPACT) for focal articular cartilage lesions of the knee

Articular cartilage defects in the knee have poor intrinsic healing capacity
and may lead to functional disability and osteoarthritis. Cartilage cell
therapy using autologous chondrocyte implantation 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, it was
withdrawn from the European Market. There is a highly unmet need for treatment
of articular cartilag defect. 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 MSCs. These cells can be mixed with a
widely used, commercially available, fibrin cell carrier and applied to the
cartilage lesion within one surgical procedure, using a minimally invasive and
eventually arthroscopic technique. In a phase I trial, we have shown that
immediate transplantation of a potent cell-based cartilage product is safe,
reduces patient morbidity and improves patient care. Therefore, we now propose
the clinical evaluation in a phase II prospective monocenter study of IMPACT
for treatment of articular cartilage defects of the knee to prove clinical
safety and feasibility.

The primary objective is to measure the level of clinical improvement and
quality of life at 6, 12 and 18 months. The secondary objective is to measure
functional repair using MRI at 6 and 18 months postoperative.

Other important objectives are clinical safety and healthcare use and costs
related to the procedure as well as the health-related work leave during the
study period.

This is a phase II prospective monocenter study, investigating efficacy and
safety of a new ATMP-product for isolated articular cartilage lesions

One-stage surgery using the Instant MSC Product accompanying Autologous
Chondron Transplantation (IMPACT)

Potential risks: graft failure and/ or migration or foreign body responce,
tissue hypertrophy (excessive growth of new tissue), and general knee surgery
related risks such as surgical site infection, arthralgia, joint crepitation,
swelling, effusion, chondropathy, synovitis, deep-vein thrombosis, pulmonary
embolism, haemarthrosis and arthrofibrosis. See section 7.2 for definitions of
AEs.

At this moment, this is the only (therapeutic) treatment option. The only
alternative is physical therapy, which does not lead to repair of the cartilage
defect.