Instant MSC Product accompanying Autologous Chondron Transplantation (IMPACT) for focal articular cartilage lesions of the knee; feasibility and safety

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, 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 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. This will reduce patient morbidity and
improve patient care through immediate transplantation of a potent cell-based
cartilage product. Therefore, we now propose the clinical evaluation in a phase
I/II prospective monocenter study of the IMPACT for treatment of articular
cartilage defects of the knee to prove clinical safety and feasibility.

The primary objective of this study is to examine clinical safety and
feasibility of the IMPACT therapy. The secondary objective is to measure the
level of clinical improvement and quality of life at 6, 12 and 18 months. The
tertiary objective of this study is to examine parameters of structural repair
one year after treatment. The quaternary objective is to assess the healthcare
use and costs related to the procedure as well as the health-related work leave
during the study period.

This is a phase I/II prospective monocenter study, investigating the
feasibility 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.

Regarding the burden for patients, this procedure is a one-stage procedure
which is an advantage compared to the conventional two-stage procedure. For the
participation 3 additional visits to the hospital are required in which the
patient will be subjected to a physical exam as well as be asked to complete
the questionnaires. Prior to treatment and at at the visit at 12 months, a
contrast MRI scan will be obtained. In addition, at twelve months an
arthroscopy with biopsy will be performed.