Clinical Trial for the Regeneration of Cartilage Lesions in the Knee
Condition: Tear; Knee, Cartilage, Articular
Study type: Interventional

Summary: 
      The purpose of this study is to investigate the efficacy of an engineered cartilage
      transplant (N-TEC) in comparison to a cell-activated matrix (N-CAM) for the treatment of
      articular cartilage lesions in the knee. The main innovations in this trial are the use of
      nasal chondrocytes and the implantation of a tissue in contrast to cells seeded on a matrix.
      The goals of the trial are to: (i) evaluate whether implantation of a more mature graft
      (tissue therapy) is beneficial for the quality and durability of the repair tissue and the
      clinical outcome, (ii)determine the potential of the mature graft to integrate with the
      adjacent cartilage and form hyaline repair tissue and (iii) assess the efficacy of each
      treatment in correlation to the characteristics of the defect (e.g. "acute" versus "chronic"
      setting).
    

Detailed description: 
      Although cartilage damages in the joint develop mostly in older people due to degeneration of
      the cartilage, they also occur regularly in young people due to accidents. Especially in
      large cartilage defects there is no spontaneous self-healing. If these defects are left
      untreated, the risk of the development of osteoarthritis later on is significantly increased.
      However, the current treatment options for these defects involve difficult operation
      techniques, require tedious rehabilitation and are limited in the application for large
      injuries and the availability/quality of the donor material. Furthermore, they often lead to
      not entirely satisfactory clinical results due to the low quality of the repair tissue. In
      many cases permanent pain and restricted mobility persist. Even the use of the new cell
      therapies has not led to satisfactory results in the long term. An innovative promising
      approach is tissue engineering, where cartilage is manufactured in the laboratory using the
      body's own cells. First results of a clinical phase I study show that the use of engineered
      nasal cartilage for the regeneration of articular cartilage (knee joint) is feasible and
      safe. In addition the preliminary clinical results regarding the efficacy are also promising.

      The goal of this phase II clinical study is to compare the efficacy of the tissue therapy
      with the one of the cell therapy. In order to achieve this the investigators will enroll 108
      patients in the study and divide them in two groups, one receiving the cell therapy and the
      other the tissue therapy. Patients must display a symptomatic, isolated cartilage lesion
      grade III-IV (according to the grading by the International Cartilage Repair Society (ICRS))
      from 2 to 8 cm2 on the femoral condyle and/or the trochlea, have to be between 18-65 years
      old and must consent in oral and written manner in order to be enrolled in the study. After
      written informed consent has been obtained, the patients will be tested to see if they comply
      with all other inclusion and exclusion criteria. Subsequently blood (72ml) and a cartilage
      biopsy (tissue sample) from the nasal septum of the patient will be taken. The cartilage
      cells (Chondrocytes) are isolated from the tissue, expanded for 2 weeks and placed on a
      collagen matrix. For the cell therapy the resulting construct will be cultured for 2 more
      days to allow the cells to adhere to the matrix. For the tissue therapy the construct will be
      cultured for 2 more weeks, to allow the cells to form cartilage tissue. After performing the
      quality tests the implant will be released by the manufacturer based on the sterility, cell
      viability and in case of the tissue therapy product the deposition of matrix. Subsequently,
      the construct will be implanted in the knee. At 6 weeks as well as 3, 12 and 24 months after
      the operation follow-ups will be performed. During the follow-ups at 12 and 24 months
      questionnaires (KOOS, Euro Quality of Life (EQ)-5d) will be filled out by the patient and
      MRIs will be performed at 3,12 and 24 months.

      While the questionnaires (especially the Knee injury and Osteoarthritis Outcome Score
      (KOOS-Score)) provide subjective information about the efficacy of the treatment, the MRIs
      will shed light on the integration of the implant in the defect and give information about
      the quality of the repair tissue. Retrospectively the data will be analyzed in correlation to
      the status of the defect at time of treatment: acute (symptoms since less than 2 years) or
      chronic (symptoms since more than 2 years). This will give an indication whether one
      treatment (cell or tissue therapy) is more effective for a defined indication (acute or
      chronic) than the other.
    

Intervention name(s): Tissue Engineered Product
Intervention type(s): Other
Intervention description(s): Implantation of tissue engineered products
Other intervention name(s): N-TEC (tissue); N-CAM (Cell activated matrix)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: nasal chondrocytes; articular chondral lesions; tissue engineering; femoral condyle; trochlea