Clinical trial NCT06576583: Implantation of Engineered Cartilage Grafts for Treatment of Patellofemoral Osteoarthritis Versus Surgical Comparators.
Official title: Randomized, Controlled, Multi-center Phase II Clinical Trial for the Treatment of Patellofemoral Osteoarthritis With Nasal Chondrocyte-based Tissue Engineered Cartilage Implantation vs Current Standard of Care
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Patellofemoral Osteoarthritis
Keywords: Nasal chondrocytes
Tissue engineering
Knee cartilage
Patellofemoral osteoarthritis
Autologous Matrix Induced Chondrogenesis (AMIC)
Patellofemoral arthroplasty (PFA)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Clinical Trial Unit, University Hospital Basel, Switzerland
name: Wuerzburg University Hospital
name: Medical University of Vienna
name: Videoreha
name: University of Oulu
name: Theracell Laboratories
name: Promove-Biotec GmbH
name: Maastricht University
name: Foundation National Reumafonds
name: Angry@Arthritis
name: University of Miami
name: Geistlich Pharma AG
name: European Union
First posted: 2024-08-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: ENCANTO is a randomized, controlled, multi-center phase II clinical trial for the treatment of patellofemoral osteoarthritis (PFOA) with an Advanced Therapy Medicinal Product (ATMP), nasal chondrocyte-based tissue engineered cartilage (N-TEC) implantation in comparison with current standard of care depending on the stage of osteoarthritis. The goal of this phase II trial is to evaluate the efficacy of N-TEC treatment in comparison to an active comparator Autologous Matrix Induced Chondrogenesis (AMIC) for early stage PFOA or patellofemoral arthroplasty (PFA) for late stage PFOA.

The N-TEC 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 multi-center phase II trial is to (i) evaluate the efficacy of N-TEC treatment in comparison to an active comparator Autologous Matrix Induced Chondrogenesis (AMIC) for early stage PFOA or patellofemoral arthroplasty (PFA) for late stage PFOA based on patient self-assessed questionnaires (Knee Injury and Osteoarthritis Outcome Score, KOOS) and (ii) verify the postulated mode of action, which is expected to be of regenerative nature and will be assessed by evaluation of disease-modification by x- ray and structural regeneration of the osteoarthritic joint destruction by MRI analysis. A total of 150 patients with early stage of PFOA (Iwano grade 1-2; 75 patients) or late stage of PFOA (Iwano grade 3-4; 75 patients) will be enrolled in 11 clinical centers and randomized to either N-TEC implantation or active comparator (AMIC or PFA).

Eligibility criteria: Inclusion Criteria:

* Patient age is ≥18 and ≤ 70 years at time of screening.
* Symptomatic PFOA grade 1-4 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.
* Patient is willing and able to give written informed consent to participate in the study and to comply with all study requirements, including attending all follow-up visits and assessments and to complete postoperative rehabilitation regimen.

Exclusion Criteria:

* Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol or in a dependency or employment with the sponsor.
* Patient is unwilling, unable or lacking the capacity to provide informed consent
* Patient is unable to undergo magnetic resonance imaging (MRI)
* 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 \> 2) or MRI or pain in the tibiofemoral joint as assessed by clinical examination
* Patient has excessive varus or valgus deformity (\>5°), unless corrected during implantation
* Patient has a symptomatic meniscus lesion (or removal exceeding ½), 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
* Any concomitant painful or disabling disease of the spine, hips, or lower limbs that would interfere with evaluation of the afflicted knee.
* Patient has a known immunological suppressive disorder or is taking immunosuppressives.
* Patient had any intra-articular injections into the affected knee within the last 3 months before baseline visit
* Instability of anterior, posterior and/or collateral ligaments
* The patient has a HIV/AIDS infection. (regulatory requirement)
* The patient has an acute Treponema pallidum (syphilis) infection. (regulatory requirement)
* The patient has an active hepatitis B or C infection with verified antigens. Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded. (regulatory requirement)
* Patient is pregnant, breast feeding or anticipates becoming pregnant within 24 months after surgery.
* Patient is currently participating or has participated in any other clinical study within 3 months prior to the screening visit.
* Patient has known current or recent history of illicit drug or alcohol abuse or dependence defined as the continued use of alcohol or drugs despite the development of social, legal or health problems.
* Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study.
* Any known allergies, especially for porcine collagen, penicillin or streptomycin (manufacturing)
* Nail-patella syndrome

Primary outcomes:
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain
timeFrame: 24 months
Secondary outcomes:
measure: Knee Injury and Osteoarthritis Outcome questionnaire
timeFrame: until 12 months
measure: Knee Injury and Osteoarthritis Outcome questionnaire
timeFrame: Until 24 months
measure: Kujala questionnaire
timeFrame: Until 24 months
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
timeFrame: Until 24 months
measure: EQ-5D-5L questionnaire
timeFrame: Until 24 months
measure: Global Rating Of Change (GROC) likert scale
timeFrame: Until 24 months
measure: Marx Activity Rating Scale (MARS) score
timeFrame: Until 24 months
measure: Morphological analysis
timeFrame: Until 24 months
measure: Collagen network organization
timeFrame: Until 24 months
measure: Osteoarthritis grading
timeFrame: Until 24 months
measure: Biovigilance
timeFrame: Until 24 months
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Orthopedic Hospital Vienna-Speising
city: Zagreb
country: Croatia
facility: University Hospital Sveti Duh
city: Berlin
country: Germany
facility: Evangelisches Waldkrankenhaus Spandau
city: Würzburg
country: Germany
facility: Orthopedic Clinic König-Ludwig-Haus
city: Milan
country: Italy
facility: IRCCS Ospedale Galeazzi-Sant'Ambrogio
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Krakow
country: Poland
facility: Zeromski hospital
city: Mölndal
country: Sweden
facility: Department of Orthopaedics, University of Gothenburg (UGOT)
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Basel
country: Switzerland
facility: Crossklinik
Study officials:
References: