Over the initial 18months, significant progress was achieved across the scientific and technical components of the project, which aims to assess the clinical efficacy and economic impact of Nasal Chondrocyte Tissue Engineered Cartilage (N-TEC) implantation in patients with symptomatic patellofemoral osteoarthritis (PFOA). This is being carried out through a multicenter, randomized, controlled Phase II clinical trial involving 150 patients across eleven clinical centers in seven EU countries and Switzerland. Patients are stratified into early- and late-stage PFOA cohorts. Early-stage patients are randomized to receive either N-TEC or Autologous Matrix-Induced Chondrogenesis (AMIC), and late-stage patients to either N-TEC or patellofemoral arthroplasty (PFA). The primary endpoint is the change in the KOOS-5 score at 24 months, with the hypothesis that N-TEC will lead to at least a 16-point improvement over AMIC and outcomes comparable to PFA. Secondary endpoints include KOOS subscales, Kujala score, WOMAC, EQ-5D-5L, VAS, safety, treatment switching, and cost-effectiveness, assessed at multiple time points.
Technically, substantial efforts were focused on ensuring harmonization and standardization of clinical and imaging procedures across all sites to enable consistent and high-quality data collection. MRI protocols were fully optimized and consolidated into the Participant Scanning Guide (Deliverable 1.1) which provides detailed technical specifications, sequence parameters, and standardized patient positioning instructions. This guide was distributed to all clinical centers to ensure radiological consistency.
In parallel, a unified physiotherapy program (Deliverable 1.2) was finalized and rolled out across all trial sites. This includes both in-clinic physiotherapist-led rehabilitation and a structured digital program that supports remote patient engagement and progress tracking. Standardized post-operative care and follow-up procedures were established, complemented by training materials to ensure methodological consistency.
Clinical data management processes were finalized, with protocols compliant with GCP and GDPR (Deliverable 6.1) put in place to ensure secure and ethical handling of patient information. All clinical, imaging, and physiotherapy data are being centrally collected and managed according to the predefined statistical analysis plan.
On the regulatory and manufacturing side, all required clinical trial authorizations were successfully obtained in participating countries (Deliverables 1.2 2.1) marking the achievement of Milestone 2. Manufacturing processes at both production facilities were validated, and harmonized GMP documentation and quality control standards were implemented (Deliverable 3.1). Regulatory questions regarding graft quality and sterility were addressed and resolved. Furthermore, additional assays including optical coherence tomography (OCT) and secretome profiling were initiated to enhance ongoing product qualification.
In the field of biomarker research, biospecimen collection protocols were standardized across sites (Deliverable 4.1) with sample collection starting post patients recruitment. Planned analyses using multiplex immunoassays will target relevant chemokines, cytokines, and growth factors with the aim of identifying molecular endotypes that correlate with therapeutic response.
Overall, the technical and scientific work performed during this reporting period has laid a solid foundation for the next phases of the clinical trial. All planned deliverables were completed, and Milestone 2 was successfully achieved. Milestone 1, corresponding to the implantation of the first N-TEC graft, is expected to reach in the thir quarter of this year with no impact on the activities.
