IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.

Study Overview
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Brief Summary
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Articular cartilage defects in the knee have a poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation (ACI) has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure which is limited by the number of chondrocytes obtained by biopsy and the dedifferentiation resulting from the expansion phase. Therefore, there is a need for improvement. A new cartilage repair technique should aim at decreasing surgical trauma, lowering complexity, improving logistics and cost-effectiveness while retaining or improving clinical outcome. Direct contact between mesenchymal stromal cells (MSCs) and dedifferentiated articular chondrocytes in vitro showed improvement of the chondrogenic phenotype of dedifferentiated articular chondrocytes. In addition, preserving the pericellular matrix of chondrocytes improves cartilage formation. These chondrons (chondrocytes with their pericellular matrix) have shown improved cartilage formation when combined with allogeneic MSCs in extensive preclinical studies. The cells are mixed with fibrin cell carrier and applied to the cartilage lesion within one surgical procedure. This will reduce patient morbidity and improve patient care through immediate transplantation of a potent cell-based cartilage product. This is a phase I/II prospective monocenter study to evaluate the safety and feasibility of the IMPACT for treatment of focal articular cartilage lesions of the knee.

Official Title
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Instant MSC Product Accompanying Autologous Chondron Transplantation (IMPACT): Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.

Conditions
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Foreign-Body Reaction, Inflammation, Effusion (L) Knee, Knee Pain Swelling

Intervention / Treatment
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* Other: Cartilage repair surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 and <45 years old Symptomatic isolated full-thickness articular cartilage lesion on the femoral condyle or trochlea. Size 2 - 8 cm2 Intact anterior cruciate ligament Exclusion Criteria: (History of) osteoarthritis, defined as Kellgren-Lawrence grade >3 as determined from appropriate X-ray. Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis) (History of) Septic arthritis. Malalignment requiring an osteotomy. (History of) total menisectomy in the target knee joint. Any surgery in the knee joint 6 months prior to study inclusion. Risk groups for MRI scanning due to the magnetic field like patients with pacemakers, nerve stimulators, metal particles, stents, clips or implants, (possible) pregnancy or breast feeding. Patients with severe anxiety for MRI scans and/or needles

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Intervention Model: Single Group Assignment
Interventional Model Description: First in man surgery: autologous chondrons are mixed with allogeneic MSCs and implanted in a fibrin glue carrier in a one-stage surgical procedure.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cartilage repair surgery<br>Single-stage cartilage repair surgery using autologous chondrons (10-20%) and allogeneic MSCs (80-90%) in a fibrin glue carrier with a dosage of two million cells/ cm2 applied once during a surgical procedure. | Other: Cartilage repair surgery<br>* Single-stage surgery, After debridement, the cartilage defect is filled with the fibrin glue carrier containing autologous chondrons and allogeneic MSCs<br>* Other names: IMPACT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Adverse Events | Adverse events rate | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement, Knee Injury and Osteoarthritis Outcome Score | Clinical improvement as measured by patient reported outcome scores. The questionnaire has been developed to evaluate the symptoms and limitations for patients with osteoarthritis. The outcome of the KOOS-scale varies from 0-100, where 0 indicates the greatest possible problems and is the worst outcome and 100 indicates no problems. | 3 and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IMPACT, Chondrons, Mesenchymal stem cells, Allogeneic MSCs, single-stage, Cartilage repair, Safety, Efficacy