Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects
Condition: Traumatic Articular Cartilage Defects in the Knee Joint
MeSH terms: Cartilage Diseases; Fractures, Stress
Study type: Interventional
Phase: Phase 3

Summary: 
      In this phase 3 clinical trial, a second generation ACI (autologous chondrocyte implantation
      technique) is compared to standard of care therapy (microfracture) to treat traumatic
      cartilage defects of the knee for efficacy and safety. The investigated study treatment
      NOVOCART 3D plus is a biphasic biological scaffold which contains cultivated chondrocytes
      derived from the patient in a previous tissue harvest procedure. Allocation to the study
      treatment is done by randomization in a ration of 2:1 in favor to ACI (investigational
      product). Follow-up data for efficacy is collected for 2 years: follow-up visits are
      performed 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months after treatment;
      additional data for safety will be collected for up to 5 years: 36, 48, and 60 months after
      treatment. The study involves knee surgery (by arthroscopy, or mini-arthrotomically for
      implantation surgery), and blood withdrawal for safety within the first year after treatment.
      Initial imaging is required at baseline. Optional MRI imaging and biomarker collection is
      done as substudy at specific sites only.
    

Detailed description: 
      For the cartilage cell product NOVOCART® 3D plus, which is used in the study described here,
      the company TETEC AG obtained an expanded production authorization from the medication
      monitoring authorities in compliance with Section 13, Para. 1 of the Medicinal Products Act
      in 2003. This entitles TETEC AG to produce the pharmaceutical product and already distribute
      it. More than 6000 patients were already successfully treated with NOVOCART® 3D in Europe
      since 2003. In order to obtain a general market authorization for NOVOCART® 3D plus, this
      control group study is conducted, in which the superiority of the safety and effectiveness of
      carrier-bound Autologous Chondrocyte Transplantation with NOVOCART® 3D plus compared to the
      standard of care microfracture surgery needs to be proven. This study further aims at
      developing and validating known and new biologic markers for the quality and clinical
      efficacy of the product as requested in the context of identity, purity and potency
      characteristics of the medicinal/investigational product.

      The patients will receive one of the therapeutic procedures in the study. The treatment
      procedure which will be used will be decided by a previously specified randomization process.
      This type of study meets the high quality requirements of the statutorily specified safety
      and quality regulations which are also referred to as "Good Clinical Practice" (GCP). The
      probability of the patient being allocated to one of the two treatments is 2:1; that is, an
      approx. 67% probability of therapy with NOVOCART® 3D plus and an approx. 33% probability of
      therapy with microfracture. Neither the patient, nor the investigator will be able to
      influence the treatment assignment.

      Patients will be screened for eligibility at the Screening Visit. Each patient will remain in
      the study for 24 months post-implant for the effectiveness assessments, and then an
      additional three years to complete the planned post-market phase. Each patient will be in the
      study for up to five years.

      Cells and tissues collected from this study will be used in other in vitro-controlled
      experiments aimed at developing and validating known and novel biologic markers to quantify
      cell quality in the context of identity, purity and potency. Prognostic values of these
      biologic markers will be examined by correlating them with clinical data collected in this
      study.
    

Intervention name(s): NOVOCART® 3D plus; Microfracture
Intervention type(s): Drug; Procedure
Intervention description(s): Two-Step intervention: 1) cartilage cells are collected from the patient during arthroscopy 2) collected cartilage cells are cultivated in a sterile environment, seeded in an organic matrix scaffold and implanted into the defect location (knee, femur); single-step treatment: defect location (knee, femur) is debrided, then bone plate is drilled mechanically to allow cells from the bone marrow to move to the defect location and to develop a scar tissue
Other intervention name(s): Matrix-associated autologous chondrocyte implantation; Microfracture according to Steadman
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Autologous Chondrocyte Transplantation; NOVOCART 3D plus; knee joint pain; safety; efficacy; treatment; TETEC; cartilage; ACT; cartilage repair; tissue; MOCART