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.
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.
Study Type
INTERVENTIONAL
Allocation
Implantation of an autologous tissue engineered cartilage graft in the patellofemoral joint for treatment of osteoarthritis.
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.
Poliklinika Ivković
Zagreb, Croatia
RECRUITINGPoliklinika Ortho Plus
Zagreb, Croatia
RECRUITINGUniversitätsklinikum Freiburg
Freiburg im Breisgau, Germany
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)
Time frame: 24 months
Biovigilance
Number of adverse events, adverse reactions based on severity, expectedness and relationship to treatment.
Time frame: until 24 months
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)
Time frame: until 24 months
Iwano classification
Osteoarthritis grade determined based on X-rays according to Iwano classification (grades 1 to 4).
Time frame: until 24 months
Kellgren Lawrence classification
Osteoarthritis grade determined based on X-rays according to Kellgren Lawrence classification (grades 1 to 4).
Time frame: until 24 months
MOCART score
Magnetic Resonance Imaging (MRI) of Cartilage Repair Tissue (MOCART) score: radiological evaluation of repair tissue. Minimum score:0; maximum score: 100.
Time frame: until 24 months
Kujala self reported questionnaire
Anterior Knee Pain scale. Minimum score: 0 Maximum score: 100 (no knee problems)
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RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
75
Orthopädische Klinik König-Ludwig-Haus
Würzburg, Germany
NOT_YET_RECRUITINGUniversity Hospital Basel
Basel, Switzerland
RECRUITINGCrossklinik
Basel, Switzerland
RECRUITINGHôpitaux universitaires de Genève
Geneva, Switzerland
RECRUITINGOspedale Regionale di Lugano
Lugano, Switzerland
RECRUITINGSportclinic, Klinik Hirslanden
Zurich, Switzerland
RECRUITINGTime frame: 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.
Time frame: 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).
Time frame: until 24 months
Visual Analogue Scale
The VAS is used by patients to assess pain based on a numbered scale going from 0 (no pain) to 10 (maximal pain).
Time frame: Unitl 24 months
Global Rating Of Change (GROC) likert scale
Widely used score to assess whether the patient condition has gotten worse, better, or stayed the same and to quantify the magnitude of that change. Minimum score: -5 ; maximal score: +5.
Time frame: until 24 months
Marx Activity Rating Scale (MARS) score
This activity-related patient-reported outcome measure is widely used to assess the activity of a patient after treatment of the knee. It assesses how often the patient performs activities (running, cutting, deceleration and pivoting) in his healthiest and more active state. Minimum score: 0; maximum score: 16
Time frame: until 24 months
Number of non responders
Number of treated patients showing an improvement in KOOS Pain below 13 on a scale of 0 to 100 after 24 months compared to baseline.
Time frame: Until 24 months
Number of treatment failures
Treatment failures are treated patients who had to switch to an alternative surgical regenerative treatment or knee replacement. This clinical deterioration is defined as reduction in the KOOS score of \> 13 after 24 months compared to baseline.
Time frame: Until 24 months
MRI Osteoarthritis Knee Score (MOAKS)
MRI Osteoarthritis Knee Score (MOAKS) is a semi quantitative score used to assess the severity and progression of osteoarthritis in the knee using magnetic resonance imaging (MRI). It evaluates various features like osteophytes, bone marrow lesions, and cartilage loss, providing a detailed picture of the disease's status.
Time frame: Until 24 months