In an effort to overcome the limitations of currently available treatments, the BIO-CHIP project aims at carrying out a phase II clinical trial (Nose To Knee II) for the treatment of traumatic cartilage lesions in the knee, with two main innovations:
- the use of autologous nasal chondrocytes as a cell source superior to articular chondrocytes and
- the delivery of a tissue graft (tissue therapy) as opposed to a cellular graft (cellular therapy).
We intend to formally test the hypothesis that implanting a mature cartilage graft will improve the clinical efficacy, leading to a significant improvement in the main primary outcome, i.e., pain and functionality.
Phase II study
We plan to enrol a total of 108 patients in clinical centres in Croatia, Germany, Italy and Switzerland:
- Universitätsspital Basel (University Hospital Basel), Basel, Switzerland;
- Universitätsklinikum Freiburg (Medical Centre University of Freiburg), Germany;
- I.R.C.C.S. Istituto Ortopedico Galeazzi (Galeazzi Orthopaedic Institute), Milan, Italy;
- Klinicka Bolnica “Sveti Duh” (University Hospital Sveti Duh), Zagreb, Croatia.
All patients (aged between 18 and 65) with a symptomatic, isolated cartilage lesion grade III-IV on the femoral condyle and/or trochlea with a total size of 2-8 cm2 will be recruited during routine clinical visits.
Complex cartilage lesions, including “kissing lesions” (i.e., when two defects are in direct contact with each other) are considered as early degenerative pathologies, with features similar to pre-osteoarthritis, and are therefore excluded for treatment by current methods. The clinical outcome for such untreatable defects is generally knee arthroplasty.
We intend to explore the possibility of extending the use of our mature cartilage grafts to these so far untreatable lesions.
While the Phase II clinical trial forms the central part of the project, and will address the specific scientific question related to the role of graft maturation on the clinical outcome, this can only take place if the individual clinics and manufacturer obtain the relevant permissions from ethical and regulatory bodies. These cover GMP (Good Manufacturing Practice) for production and characterization of the product, GCP (Good Clinical Practice) for conduct of the clinical trial and GDP (Good Distribution Practice) for distribution of human products from the hospitals to the manufacturer back again.
We aim to develop new characterization methods for starting materials, intermediates and final products (i.e., in process controls and release criteria) essential for future marketing and control of the manufacturing process. Assays performed during production will be correlated with the clinical outcome to evaluate the significance of the respective analysis.
In order to assess the suitability of using the tissue engineered cartilage graft in biomechanically challenging situations, such as the yet untreatable kissing lesions, a pre-clinical study will also be performed.
We will also address the financial and marketing issues required to commercialise the tissue engineered cartilage graft.