Evaluation of N-TEC Implantation for Patellofemoral Osteoarthritis: A Randomized, Controlled, Multicenter Phase II Clinical Trial

The primary objective of this study is to evaluate the **mean KOOS Pain Change** from baseline to 24 months between groups in patients with patellofemoral osteoarthritis. This is clinically relevant as it aims to assess the efficacy of nasal chondrocyte-based engineered cartilage implantation in reducing pain, which is a significant symptom impacting the quality of life in individuals with this condition.

Secondary objectives include:

• Assessing mean KOOS subscales (Symptoms, Activity of Daily Living, Sports & Recreation, Quality of Life).
• Determining the number of subjects non-responding (improvement in KOOS Pain < 13 on a scale of 0-100) at 24 months.
• Evaluating the number of SARs and SUSARs to assess safety.
• Measuring the Global Rating Of Change (GROC) Likert scale at 6, 12, and 24 months.
• Assessing the Marx Activity Rating Scale (MARS) at 6, 12, and 24 months.
• Using MRI Osteoarthritis Knee Score (MOAKS) for radiological evaluation of osteoarthritis at 6, 12, and 24 months.
• Evaluating MRI of Cartilage Repair Tissue (MOCART) for radiological evaluation of repair tissue at 6, 12, and 24 months.
• Determining osteoarthritis grade according to Iwano and Kellgren/Lawrence classification at 6, 12, and 24 months.
• Assessing the Kujala Anterior Knee Pain Scale at 6, 12, and 24 months.
• Evaluating WOMAC at 6, 12, and 24 months.
• Assessing EQ-5D at 6, 12, and 24 months.
• Measuring VAS at 6, 12, and 24 months.

The clinical trial involves a total of **59 participants** diagnosed with **patellofemoral osteoarthritis**. The study population includes both male and female subjects, with an age range corresponding to category code 3, which typically represents adults. Participants were selected based on specific inclusion criteria, such as having symptomatic patellofemoral osteoarthritis grade 1-3 according to the Iwano Classification and chondropathy grade 3-4 according to the ICRS classification. Additionally, participants must have a baseline score of less than 60 on the KOOS Pain subjective knee evaluation and a free range of motion of the affected knee joint or ≤ 5° of extension loss with a minimum of 125° flexion. The trial does not include a vulnerable population, and both genders are represented. Relevant lifestyle considerations, such as diet and physical activity, are not specified. The selection process ensures that non-surgical standard of care options, except for PRP, have been exhausted for all participants. The trial aims to assess the mean KOOS Pain change from baseline to 24 months between groups.

The clinical trial is designed to evaluate the efficacy and safety of **tissue engineered cartilage** implantation in patients with **patellofemoral osteoarthritis**. This is a randomized, controlled, multi-center phase II trial. The study aims to compare the mean change in KOOS Pain from baseline to 24 months between groups receiving the investigational product, N-TEC, and those receiving platelet-rich plasma (PRP). The trial is expected to commence recruitment on September 1, 2024, and conclude by August 31, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as symptomatic PFOA grade 1-3 according to Iwano Classification and a baseline KOOS Pain score of less than 60. Following successful screening, participants will be randomized to receive either the investigational product or the control treatment. The investigational product involves the implantation of tissue engineered cartilage based on autologous nasal chondrocytes.

Study visits will occur at baseline, and follow-up visits are scheduled at 6, 12, and 24 months post-implantation. These visits will include assessments of primary and secondary endpoints, such as KOOS Pain, Kujala Anterior Knee Pain Scale, WOMAC Score, and MRI evaluations. The end-of-study visit will coincide with the 24-month follow-up, marking the completion of the participant's involvement in the trial.

Participant involvement is expected to last approximately 24 months. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial will adhere to rigorous standards to ensure the safety and well-being of participants throughout the study duration.

The clinical trial involves the use of an **experimental medication** known as **N-TEC**, which is a tissue-engineered cartilage implant. This product is based on autologous nasal chondrocytes and is designed for the treatment of patellofemoral osteoarthritis. The pharmaceutical form of N-TEC is an **implant**, and it is administered via **implantation**. The maximum daily dose and total dose amount are both set at 40 cm², with a maximum treatment period of 1 day. The active substance, N-TEC, is classified as a structurally diverse substance used in cell therapy. The product is developed by Universitaetsspital Basel and is not a pediatric formulation.

In addition to the experimental treatment, the study utilizes a **device** known as ChondroGide, which is a collagen type I/III membrane derived from porcine sources. This device is used in conjunction with the N-TEC implant and has a CE mark, indicating compliance with European health, safety, and environmental protection standards. The ChondroGide membrane serves as a scaffold to support the implantation of the engineered cartilage.

Participant compliance with the treatment regimen is monitored throughout the study. The trial aims to evaluate the mean change in KOOS Pain from baseline to 24 months between groups, providing insights into the efficacy of the N-TEC implant in managing symptoms of patellofemoral osteoarthritis.

Efficacy in this clinical trial will be assessed primarily through the **KOOS Pain** score, which measures the change from baseline to 24 months between groups. The primary endpoint is the comparison of the mean change in KOOS Pain from baseline to 24 months, with a specific focus on the difference between the N-TEC and PRP groups, aiming for a change greater than 15. Secondary endpoints include the mean KOOS Pain at 6 and 12 months, as well as other KOOS subscales such as Symptoms, Activity of Daily Living (ADL), Sports & Recreation (Sports), and Quality of Life (QOL) at 6, 12, and 24 months. Additional assessments will be conducted using the Kujala Anterior Knee Pain Scale, WOMAC Score, EQ-5D-5L, and VAS at the same intervals.

Radiological evaluations will be performed using the MRI Osteoarthritis Knee Score (MOAKS) and MRI of Cartilage Repair Tissue (MOCART) at 6, 12, and 24 months to assess osteoarthritis and repair tissue, respectively. The osteoarthritis grade will be classified according to Iwano and Kellgren/Lawrence at these timepoints. The number of treatment failures and subjects not responding, defined as an improvement in KOOS Pain of less than 13 on a scale of 0-100, will be recorded at 24 months. The Global Rating Of Change (GROC) Likert scale and MARS will also be evaluated at 6, 12, and 24 months. Safety will be monitored by recording the number of SARs and SUSARs throughout the trial.