Phase II Randomized Controlled Trial of Nasal Chondrocyte-Based Tissue Engineered Cartilage Implantation for Patellofemoral Osteoarthritis Treatment

The primary objective of this phase II clinical trial is to evaluate whether the implantation of **N-TEC** (nasal chondrocyte-based tissue engineered cartilage) results in a superior clinical outcome compared to the current standard of care, AMIC, in patients with **patellofemoral osteoarthritis**. This will be assessed by measuring the change in the KOOS-5 score from baseline to 24 months. The clinical relevance of this objective lies in determining the efficacy of N-TEC in improving joint function and patient quality of life over the standard treatment.

Secondary objectives include:

• Assessing the development of patients' recovery over time at 6, 12, and 24 months using various questionnaires and subscores, including WOMAC, MARS, Kujala, EQ-5D, VAS, KOOS, GROC, and patient satisfaction.
• Conducting radiological analysis (MRI, X-ray) to evaluate the integration of the graft, maturation of the repair tissue, and disease progression or remission.
• Evaluating the number of treatment failures at 24 months.
• Assessing safety based on the number of SARs (Serious Adverse Reactions) and SUSARs (Suspected Unexpected Serious Adverse Reactions).

The clinical trial involves a total of **28 participants** diagnosed with **patellofemoral osteoarthritis**. The study population includes both male and female subjects, with an age range of 18 to 70 years. Participants were selected based on specific criteria, including symptomatic patellofemoral osteoarthritis grade 1-4 according to the Iwano Classification and chondropathy grade 3-4 as per the ICRS classification. All participants have a baseline score of less than 75 on the KOOS-5 subjective knee evaluation and possess a free range of motion in the affected knee joint or have no more than 5 degrees of extension loss and a minimum of 125 degrees flexion. The trial does not include a vulnerable population, and all participants have provided written informed consent. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.

The clinical trial is a **randomized**, controlled, multi-center phase II study designed to evaluate the efficacy and safety of nasal chondrocyte-based tissue engineered cartilage implantation (N-TEC) compared to the current standard of care for the treatment of **patellofemoral osteoarthritis**. The primary objective is to assess whether N-TEC implantation results in superior clinical outcomes, as measured by the change in the KOOS-5 score from baseline to 24 months, compared to the comparator treatment. The trial is expected to run until December 31, 2029, with recruitment starting on April 1, 2025.

Participants will be involved in the study for a duration of 24 months, during which they will undergo a series of study visits. The sequence of visits includes an initial screening visit to confirm eligibility based on criteria such as age, symptomatic PFOA grade, and baseline KOOS-5 score. Following the screening, participants will be randomized to receive either the N-TEC implantation or the comparator treatment. Follow-up visits are scheduled at baseline, 6, 12, and 24 months to monitor the primary and secondary endpoints, which include various clinical scores and imaging assessments. The end-of-study visit at 24 months will conclude the participant's involvement in the trial.

Participants may be withdrawn from the study early if they experience significant adverse reactions, fail to comply with study procedures, or choose to withdraw consent. The trial employs a double-blind design to ensure unbiased results, with neither participants nor investigators aware of the treatment allocation. The study will utilize a tissue engineered product, N-TEC, which is administered via **implantation**. The maximum daily and total dose of the product is 40 cm², with a treatment period limited to one day. The trial will collect data on safety, including the number of serious adverse reactions and treatment failures, to comprehensively evaluate the therapeutic potential of N-TEC in managing patellofemoral osteoarthritis.

The clinical trial involves the use of an **experimental medication** known as N-TEC, which is a tissue-engineered cartilage implant. The pharmaceutical form of N-TEC is an **implant**, specifically designed for the treatment of patellofemoral osteoarthritis. The active substance in N-TEC is derived from nasal chondrocytes, classified as a structurally diverse substance used in cell therapy. The maximum daily and total dose of N-TEC is 40 cm², with a treatment period limited to one day. The route of administration is through **implantation**, and the product is not formulated for pediatric use. The N-TEC implant is developed by Universitaetsspital Basel and is intended to provide a superior clinical outcome compared to the current standard of care.

The comparator treatment in this study is the current standard of care, known as Autologous Matrix-Induced Chondrogenesis (AMIC). This non-experimental treatment serves as the control against which the efficacy of N-TEC is measured. The trial aims to assess the change in the KOOS-5 score from baseline to 24 months, comparing the outcomes of N-TEC implantation with those of AMIC. The study is designed to collect data on both treatments, although only minimal differences in the change of KOOS-5 scores between N-TEC and AMIC are anticipated.

To ensure accurate monitoring of participant compliance and dosing schedules, the trial employs a device known as Chondrogide, a collagen type 1 and 3 membrane, which is used in conjunction with the N-TEC implant. This device has received CE marking, indicating its compliance with European health, safety, and environmental protection standards. The use of Chondrogide is integral to the implantation process, facilitating the proper application and integration of the N-TEC implant within the treatment site.

Efficacy in this phase II clinical trial will be assessed primarily through the change in the KOOS-5 subjective score from baseline to the 24-month follow-up. The KOOS-5, or Knee injury and Osteoarthritis Outcome Score, is a validated scale used to evaluate the patient's opinion about their knee and associated problems. This primary endpoint will determine whether the implantation of N-TEC leads to a superior clinical outcome compared to the current standard of care, AMIC, in patients with patellofemoral osteoarthritis.

Secondary endpoints include a range of additional measures to provide a comprehensive assessment of efficacy. These include mean KOOS subscores at baseline, 6, 12, and 24 months, as well as the Kujala Anterior Knee Pain Scale, WOMAC Score, EQ-5D-5L, GROC Likert scale, Marx Activity Rating Scale, and VAS Score, all measured at the same timepoints. Patient satisfaction will be evaluated at 24 months. Imaging assessments, including MRI and X-ray, will be conducted at baseline, 6, 12, and 24 months to provide objective data on structural changes. Safety will be monitored by recording the number of serious adverse reactions (SARs) and suspected unexpected serious adverse reactions (SUSARs), along with the number of treatment failures at 24 months.