Clinical trial NCT06163573: Treatment of Patellofemoral Osteoarthritis With Engineered Cartilage.
Official title: Treatment of Patellofemoral Osteoarthritis With Nasal Chondrocyte-based Engineered Cartilage Implantation in a Randomized, Controlled, Multi-center Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Patellofemoral Osteoarthritis
Keywords: Nasal chondrocytes
Tissue engineering
Knee cartilage
Patellofemoral osteoarthritis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Clinical Trial Unit, University Hospital Basel, Switzerland
name: Wuerzburg University Hospital
First posted: 2023-12-11
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental group: biological: Autologous nasal chondrocytes and ECM proteins Control group: Platelet rich plasma injections
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain
timeFrame: 24 months
Secondary outcomes:
measure: Biovigilance
timeFrame: until 24 months
measure: Knee Injury and Osteoarthritis Outcome questionnaire
timeFrame: until 24 months
measure: Iwano classification
timeFrame: until 24 months
measure: Kellgren Lawrence classification
timeFrame: until 24 months
measure: MOCART score
timeFrame: until 24 months
measure: Kujala self reported questionnaire
timeFrame: until 24 months
measure: EQ5d questionnaire
timeFrame: until 24 months
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
timeFrame: until 24 months
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: Poliklinika Ivković
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Würzburg
country: Germany
facility: Orthopädische Klinik König-Ludwig-Haus
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Basel
country: Switzerland
facility: Crossklinik
city: Bern
country: Switzerland
facility: Inselspital
city: Genève
country: Switzerland
facility: Hôpitaux universitaires de Genève
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
city: Zürich
country: Switzerland
facility: Sportclinic, Klinik Hirslanden
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Marcus Mumme, Dr
role: PRINCIPAL_INVESTIGATOR
References: