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

Overview

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).

Interventions

• Biological Engineered cartilage graft (N-TEC)
  Nasal chondrocytes based tissue engineered cartilage
• Procedure Autologous Matrix Induced Chondrogenesis (AMIC)
  Autologous Matrix Induced Chondrogenesis is performed through bone drilling and covering with Chondro-Gide® to attract bone marrow stem cells
• Procedure Patellofemoral Arthroplasty (PFA)
  Surgical implantation of a medical device, Zimmer Gender Solutions Patellofemoral Joint Prosthesis.

Primary outcome measures

• Knee Injury and Osteoarthritis Outcome Score (KOOS)-5 [Time frame: 24 months]

Secondary outcome measures (11)

• Knee Injury and Osteoarthritis Outcome questionnaire [Time frame: until 24 months]
• Knee Injury and Osteoarthritis Outcome questionnaire [Time frame: Until 24 months]
• Kujala questionnaire [Time frame: Until 24 months]
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score [Time frame: Until 24 months]
• EQ-5D-5L questionnaire [Time frame: Until 24 months]
• Global Rating Of Change (GROC) likert scale [Time frame: Until 24 months]
• Marx Activity Rating Scale (MARS) score [Time frame: Until 24 months]
• Morphological analysis [Time frame: Until 24 months]
• Collagen network organization [Time frame: Until 24 months]
• Osteoarthritis grading [Time frame: Until 24 months]
• Biovigilance [Time frame: Until 24 months]

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 <75 on the KOOS-5 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.
• Minimum values for women: Haemoglobin 120g/l, Platelets 150G/l, INR<1.3
• Minimum values for men: Haemoglobin 140g/l, Platelets 150G/l, INR<1.3
• Patients have failed to demonstrate adequate response to non-pharmacological interventions (e.g. structured land-based exercise programs) and pharmacological first-line treatment such as topical NSAIDs

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 systemic 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.
• Known allergies for porcine collagen (scaffold), penicillin or streptomycin (manufacturing)
• Nail-patella syndrome
• Patients who will likely benefit from conservative therapy, such as physiotherapy, medical training therapy and pain medication
• Patients with increased anesthesiological and surgical risks (e.g. known or predicted difficult airway, myocardial infarction <60 days prior to surgery)
• Patients with increased bleeding risk (e.g. coagulopathies)
• Patients on anticoagulants whose anticoagulant therapy cannot be interrupted as appropriate to the given agent(s) and underlying condition
• Patients with any active infections

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Germany · 2 centers

• Evangelisches Waldkrankenhaus Spandau — Berlin
• Orthopedic Clinic König-Ludwig-Haus — Würzburg

Italy · 2 centers

• IRCCS Ospedale Galeazzi-Sant'Ambrogio — Milan
• Fondazione Policlinico Universitario Campus Bio-Medico — Rome

Switzerland · 2 centers

• University Hospital Basel — Basel
• Crossklinik — Basel

Austria · 1 center

• Orthopedic Hospital Vienna-Speising — Vienna

Croatia · 1 center

• University Hospital Sveti Duh — Zagreb

Netherlands · 1 center

• Maastricht University Medical Center — Maastricht

Poland · 1 center

• Zeromski hospital — Krakow

Sweden · 1 center

• Department of Orthopaedics, University of Gothenburg (UGOT) — Mölndal

Identifiers

NCT: NCT06576583 · 2024-513683-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗