Treatment of Patellofemoral Osteoarthritis With Engineered Cartilage.

Study Overview
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Brief Summary
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The purpose of this investigator-initiated study is to assess the efficacy of treating patellofemoral osteoarthritis with an Advanced Therapy Medicinal Product (ATMP), autologous nasal chondrocyte tissue engineered cartilage (N-TEC), in comparison with a standard therapy using platelet rich plasma injections. The engineered cartilage graft is obtained by culturing expanded autologous nasal chondrocytes within a collagen type I/III membrane.

Detailed Description
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Knee osteoarthritis (OA) is one of the most common causes for pain and disability with over 260 million people affected worldwide. Recent studies found that knee OA often starts in the patello-femoral compartment of the knee (PFOA) and is diagnosed in  39% of people with knee pain aged above 30 years. Thus, PFOA and progression to full OA plays a crucial role in the reduction of quality of life of many people and in the raise of healthcare costs. The goal of this phase II trial is to (i) evaluate the efficacy of autologous Nasal Chondrocytes Tissue Engineered Cartilage (N-TEC) in comparison to an active comparator (Platelet Rich Plasma (PRP) injections) based on patients' self-assessed outcome scores (Knee Osteoarthritis Outcome Score (KOOS Pain), and to (ii) verify tissue regeneration as the postulated mode of action and thus the disease-modifying properties of the graft, as previously indicated in animal studies (x-ray, MRI). This proposed phase II trial will evaluate whether N-TEC improves the clinical efficacy, leading to an increase of at least 15 points higher in the main primary outcome (KOOS (pain) change at 24 months) than the comparator group. Secondary endpoints will include amongst others KOOS subscales (symptoms, pain, activity of daily living (ADL), sports, Quality of Life (QOL)), Kujala Anterior Knee Pain Scale, Western Ontario and McMaster Universities Osteoarthritis score (WOMAC), Marx Activity Rating Scale (MARS) and EQ-5d assessment at 6, 12 and 24 months compared to baseline and between groups. Further secondary endpoints will be the number of subjects non-responding to treatment (i.e., improvement in KOOS Pain below 13 units on a scale of 0-100) and treatment failures (deterioration of more than 13 points compared to baseline or switching to other regenerative treatments or joint replacement to evaluate efficacy). Adverse events will be recorded during the full course of the trial to assess safety. This will require enrolling a total of 75 patients in a multicenter, prospective study involving 9 clinical centers.

Official Title
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Treatment of Patellofemoral Osteoarthritis With Nasal Chondrocyte-based Engineered Cartilage Implantation in a Randomized, Controlled, Multi-center Phase II Clinical Trial

Conditions
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Patellofemoral Osteoarthritis

Intervention / Treatment
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* Biological: N-TEC
* Biological: Platelet rich plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic PFOA grade 1-3 according to Iwano Classification Chondropathy Grade 3-4 according to ICRS classification of the patella, trochlea femoris or both Baseline score of <60 on the KOOS Pain subjective knee evaluation. Free range of motion of the affected knee joint or ≤ 5° of extension loss and minimum 125° flexion. Exclusion Criteria: Intra operative exclusion criteria: Advanced OA of tibiofemoral compartment of the knee Prior surgical treatment of the target knee within 12 months (Note: prior diagnostic arthroscopy with debridement and lavage are acceptable within 12 months). Radiologically apparent degenerative joint disease of the tibiofemoral joint as determined by X-ray (Kellgren and Lawrence grade >1) or MRI or pain in the tibiofemoral joint (clinical examination) Excessive varus or valgus deformity (>5°) Symptomatic meniscus lesion, as indicated by clinical examination (joint line tenderness and McMurray test positive) and MRI. Patient has a body mass index (BMI) >35 kg/m2. Patient has chronic rheumatoid arthritis, and/or infectious arthritis Patellar dislocation in the last 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental group: biological: Autologous nasal chondrocytes and ECM proteins Control group: Platelet rich plasma injections
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-TEC<br>N-TEC is based on autologous nasal chondrocytes expanded and further cultured on type I/III collagen membranes for 2 weeks to allow cells to produce extracellular matrix containing cartilage specific proteins. The IMP is implanted in the knee at the patellofemoral joint. | Biological: N-TEC<br>* Implantation of an autologous tissue engineered cartilage graft in the patellofemoral joint for treatment of osteoarthritis.<br>* Other names: Engineered cartilage graft;|
| Active Comparator: Platelet Rich Plasma<br>Total of 3 injections of about 5 ml each of platelet rich plasma (PRP), autologous Conditioned Plasma ACP®, Arthrex, one injection per week for three consecutive weeks. | Biological: Platelet rich plasma<br>* Injection of an autologous Conditioned Plasma ACP® on the basis of one injection per week for three consecutive weeks. Conditioned Plasma ACP®, Arthrex, one injection per week for three consecutive weeks.<br>* Other names: PRP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain | mean change in Knee Injury and Osteoarthritis Outcome Score for pain from baseline to 24 months between groups Minimum score: 0 Maximum score :100 (higher score means no knee problems) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcome questionnaire | patient self reported questionnaire for symptoms, activity of daily life, sports and quality of life Minimum score: 0 Maximum score: 100 (higher score means no knee problems) | until 24 months | 
| Radiological assessment | X rays and MRI | until 24 months | 
| Biovigilance | Number of adverse events, adverse reactions based on severity, expectedness and relationship to treatment. | until 24 months | 
| Kujala self reported questionnaire | Anterior Knee Pain scale. Minimum score: 0 Maximum score: 100 (no knee problems) | until 24 months | 
| EQ5d questionnaire | patient self reported questionnaire including five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. | until 24 months | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score | Self reported questionnaire to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints. The instrument contains 24 items measuring 3 sub-scales: physical function (17 items), pain (5 items), and stiffness (2 items). | until 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasal chondrocytes, Tissue engineering, Knee cartilage, Patellofemoral osteoarthritis