Safety and Efficacy With NOVOCART® Disc Plus (ADCT) for the Treatment of Degenerative Disc Disease in Lumbar Spine
Condition: Intervertebral Disc Displacement; Intervertebral Disc Degeneration
MeSH terms: Intervertebral Disc Degeneration; Intervertebral Disc Displacement
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      NOVOCART® Disc plus is being investigated to explore its clinical applicability, safety and
      efficacy in the repair of a herniated disc with an indication for an elective sequestrectomy,
      and of the adjacent degenerated disc, if present. The objective of this clinical study is to
      provide basis for a confirmatory study design (endpoints, methodologies) (Phase II), and to
      develop a safety profile (Phase I). 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.
    

Detailed description: 
      This is a classical Phase II study with an implicated Phase I part. The Phase I/II
      combination study is a non-confirmatory study aimed at gathering preliminary clinical
      information on NOVOCART® Disc plus used in a new indication in the repair of a herniated
      disc. It will be conducted in a prospective, multicenter, unmasked, clinical trial including
      120 subjects randomized to NOVOCART® Disc plus (NDplus, 60 subjects), media NOVOCART® Disc
      basic with no active cell component (NDbasic, 36 subjects) and to standard of care (SC)
      sequestrectomy as control (24 subjects). 24 patients will be enrolled in Phase I of the study
      (12 NDplus, 12 NDbasic) and 96 patients in Phase II (48 NDplus, 24 NDbasic, 24 SC).

      All subjects will be evaluated at 1.5-, 3-, 6-, 12-, 24-, 36-, 48-months post-t0 examination
      in the SC study arm and 1.5-, 3-, 6-, 12-, 24-, 36-, 48-months post-t5 examination in the
      NDplus and NDbasic study arms, and then 5 years post-t0/t5 to collect long-term clinical
      data. Efficacy measurements for functional improvement will be evaluated among NDplus,
      NDbasic and SC. Physiological effects observed from MRI measurements will be compared between
      appropriate treatments depending on expected treatment mechanisms. Safety data of NDplus will
      be combined with NDbasic to contrast against SC on procedure related risks and NDplus against
      NDbasic and SC together on graft-related adverse experiences.

      To optimize the usefulness of clinical information, data collected in the study may be
      analyzed and reviewed continuously. Early findings may be used to modify the study design
      when deemed appropriate and acceptable by the Sponsor's medical advisors. Data-driven
      adaptive actions include but are not limited to stopping enrollment early. The Sponsor will
      inform regulatory bodies, Ethic Committees, and investigators before implementing study
      design modifications.

      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.

      The study will follow each subject for a total of five years post-t0 examination in the SC
      study arm and post-t5 examination in the NDplus and NDbasic study arms to obtain long-term
      performance data.

      Patients must have a single-level acute disc herniation with an indication for an elective
      sequestrectomy. They may further have corresponding disc degeneration in the proximal
      adjacent segment (Pfirrmann Score Stage 3-4). A total of 120 adults will be enrolled in this
      study.

      Each patient will remain in the study for 5 years post t0/t5 examination to complete the
      planned follow-up phase. It is expected to take 6 years and five months to collect all
      required data for this study.
    

Intervention name(s): NOVOCART® Disc plus; NOVOCART® Disc basic
Intervention type(s): Drug; Device
Intervention description(s): Autologous Disc Chondrocyte Transplantation System (ADCT); ADCT (Media with no active cell component)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: degenerative disc; herniated disc; sequestrectomy; Autologous Disc Chondrocyte Transplantation; nucleotomy; safety; efficacy; treatment; lumbar spine; low back pain; adjacent degenerative disc; black disc; NOVOCART