Periodic Reporting for period 1 - ENCANTO (ENgineered CArtilage from Nose for the Treatment of Osteoarthritis (ENCANTO))
Période du rapport: 2024-01-01 au 2025-06-30
Knee osteoarthritis (OA) is a leading cause of pain and disability, affecting over 500 million people worldwide. With ageing populations and rising obesity, its prevalence and socio-economic impact will grow. Current treatments are limited to pain relief or joint replacement, with no therapies able to halt or reverse disease progression — a major unmet need.
ENCANTO addresses this by developing N-TEC, an advanced therapy medicinal product (ATMP) for the biological reconstruction of the patellofemoral joint in patients with patellofemoral OA (PFOA). N-TEC, a tissue-engineered cartilage implant based on autologous nasal chondrocytes and a collagen membrane, has shown success in repairing focal cartilage lesions. ENCANTO will now test its potential as the first disease-modifying OA therapy in a broader patient group.
The project’s core is an international, multicenter, randomized controlled phase II trial assessing N-TEC’s clinical efficacy in PFOA. In parallel, patient-derived samples will be analyzed to identify molecular endotypes and biomarkers linked to positive outcomes, paving the way for personalized OA treatment.
ENCANTO brings together a multidisciplinary consortium in tissue engineering, orthopaedics, rehabilitation, regulatory science, health economics, commercialization, and patient advocacy. Social sciences and humanities experts will ensure ethical frameworks, patient-centered design, and socio-economic evaluation. Health economists will assess cost-effectiveness and access pathways, while patient representatives will ensure outcomes are meaningful in practice.
If successful, ENCANTO will deliver the first regenerative, disease-modifying OA treatment, improving patient mobility and quality of life, reducing healthcare costs, and strengthening Europe’s leadership in ATMP development. The knowledge gained could also be applied to other OA-affected joints, amplifying societal benefits.
ENCANTO addresses this by developing N-TEC, an advanced therapy medicinal product (ATMP) for the biological reconstruction of the patellofemoral joint in patients with patellofemoral OA (PFOA). N-TEC, a tissue-engineered cartilage implant based on autologous nasal chondrocytes and a collagen membrane, has shown success in repairing focal cartilage lesions. ENCANTO will now test its potential as the first disease-modifying OA therapy in a broader patient group.
The project’s core is an international, multicenter, randomized controlled phase II trial assessing N-TEC’s clinical efficacy in PFOA. In parallel, patient-derived samples will be analyzed to identify molecular endotypes and biomarkers linked to positive outcomes, paving the way for personalized OA treatment.
ENCANTO brings together a multidisciplinary consortium in tissue engineering, orthopaedics, rehabilitation, regulatory science, health economics, commercialization, and patient advocacy. Social sciences and humanities experts will ensure ethical frameworks, patient-centered design, and socio-economic evaluation. Health economists will assess cost-effectiveness and access pathways, while patient representatives will ensure outcomes are meaningful in practice.
If successful, ENCANTO will deliver the first regenerative, disease-modifying OA treatment, improving patient mobility and quality of life, reducing healthcare costs, and strengthening Europe’s leadership in ATMP development. The knowledge gained could also be applied to other OA-affected joints, amplifying societal benefits.
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.
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.
N-TEC offers a regenerative treatment for patients over 55 with large cartilage defects and PFOA—cases where current therapies are limited to symptom management or joint replacement. Unlike existing options, N-TEC targets true tissue restoration, addressing a major unmet need in advanced osteoarthritis (Kellgren & Lawrence > 2), particularly in populations excluded from current regenerative approaches. It has the potential to improve PFOA management by delaying or avoiding joint replacement, which carries higher revision rates and poorer outcomes, especially in younger patients. While the main results are pending, the anticipated impact outlined in the grant agreement remains highly relevant.