Over the initial 30 months, significant progress was achieved across the scientific and technical components of the ENCANTO 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). The project is conducted through a multicenter, randomized, controlled Phase II clinical trial involving 150 patients across eleven clinical centres in seven EU countries and Switzerland. Patients are stratified into early- and late-stage PFOA cohorts. Early-stage patients are randomized to N-TEC or Autologous Matrix-Induced Chondrogenesis (AMIC), while late-stage patients are randomized to N-TEC or patellofemoral arthroplasty (PFA). The primary endpoint is change in KOOS-5 at 24 months, with secondary endpoints including KOOS subscales, Kujala, WOMAC, EQ-5D-5L, VAS, safety, treatment switching and cost-effectiveness.
During the last 12 months, major progress was achieved in clinical trial implementation, N-TEC manufacturing and quality control, imaging and clinical data collection, biomarker samples collection and health economic evaluation. Despite delays in recruitment and activation of some sites, mitigation measures were implemented. The clinical trial became fully operational and the first N-TEC implantation milestone (MS1) was successfully achieved in October 2025.
Patient screening, recruitment, randomization, treatment and follow-up were initiated across participating centres. Harmonized clinical procedures established during PR1 were implemented, including standardized clinical outcome assessments, radiological evaluation, data collection and post-operative rehabilitation. Clinical data are centrally collected through REDCap according to the predefined study procedures and statistical analysis plan. Digital rehabilitation was implemented through the Videoreha platform to support standardized remote rehabilitation and follow-up. Recruitment was continuously monitored, and MS3, concerning verification of enrolment rates and implementation of corrective measures, was achieved. In response to recruitment delays, recruitment targets and resources were redistributed towards higher-performing centres.
Clinical and imaging activities progressed according to the harmonized procedures established during PR1. MRI datasets were collected and processed using predefined acquisition parameters and standardized protocols, ensuring consistency across centres and supporting assessment of structural and clinical outcomes. Regulatory and clinical quality activities continued throughout the reporting period, including site activation, monitoring, safety reporting and management of protocol and IMP-related modifications in accordance with GCP and applicable regulatory requirements.
N-TEC manufacturing progressed substantially, with clinical-grade grafts successfully produced at the Basel and Würzburg facilities for patients enrolled in the trial. Manufacturing procedures were further harmonized between the two sites. Replacement of human platelet lysate, representing a critical manufacturing change, was successfully evaluated and validated, ensuring continuity and robustness of production. Quality control activities advanced through evaluation of non-invasive graft characterization approaches, particularly Optical Coherence Tomography (OCT) and glycosaminoglycan (GAG) measurements. The OCT comparability milestone (MS4) was partially achieved, with further validation activities ongoing.
Biomarker activities progressed from protocol standardization to biological sample collection. Harmonized SOPs for collection, processing and storage of serum, plasma, PBMC and secretome samples were finalized and implemented across participating sites. Sample collection is ongoing and will support planned multiplex analyses of chemokines, cytokines and growth factors. Integration of biomarker data with clinical and imaging outcomes will support identification of molecular profiles associated with treatment response and potential patient endotypes.
Preparatory activities for the health economic evaluation were also initiated, including a systematic literature review, analysis of quality-of-life data and development of a patient preference study. These activities establish the methodological basis for evaluating the cost-effectiveness and economic impact of N-TEC alongside the clinical trial.
Overall, the first 30 months established a strong scientific and technical foundation for ENCANTO and enabled transition into active clinical implementation. Key achievements include the first N-TEC implantation (MS1), operationalization of recruitment, treatment and follow-up, achievement of MS3, continued production of clinical-grade N-TEC grafts at both manufacturing sites, advancement of quality control strategies, implementation of harmonized biomarker sampling and initiation of the health economic evaluation. Recruitment delay remains the main operational challenge, but corrective measures have been implemented and the trial continues to progress towards its scientific and clinical objectives.
