Clinical Trial: Safety and Efficacy With NOVOCART® Disc Plus (ADCT) for the Treatment of Degenerative Disc Disease in Lumbar Spine

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Prospective Randomized Multicentre Phase I/II Clinical Trial to Evaluate Safety and Efficacy of NOVOCART® Disc Plus Autologous Disc Chondrocyte Transplantation (ADCT) in the Treatment of Nucleo

Brief 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 Summary:

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 impl
Sponsor: Tetec AG

Current Primary Outcome:

  • Oswestry Disability Index (ODI) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 12-months follow-up ]

    Primary efficacy variable.

    Early evaluation for efficacy will be performed when all patients completed scheduled 12-months follow-up visit (Interim analysis).

  • Oswestry Disability Index (ODI) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 24-months follow-up ]

    Primary efficacy variable.

    Primary evaluation for efficacy will be performed when all patients completed scheduled at 24-months follow-up visit (Interim analysis).

  • Oswestry Disability Index (ODI) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) to 60-months follow-up ]

    Primary efficacy variable.

    Final analysis will be performed when all patients completed scheduled 60-months follow-up visit.



Original Primary Outcome: Oswestry Disability Index (ODI) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

Primary efficacy variable.

Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.



Current Secondary Outcome:

  • MRI-signal (disc height, disc volumetry, signal intensity) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Oswestry Disability Index [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • VAS for back pain and leg pain [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Health-related quality of life as measured by the SF-36 [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Healthy Questionnaire EQ-5D [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Neurological status [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Functional status [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Return to work (days) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Analgesic Medication Use during the previous 14-day-time period [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

    Secondary efficacy variable

    Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

  • Physician assessments of ease of transplantation [ Time Frame: transplantation ]

    Outcome to quantify feasibility of procedure

    When all NDplus and NDbasic patients completed transplantation proced

    Original Secondary Outcome:

    • MRI-signal (disc height, disc volumetry, signal intensity) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Oswestry Disability Index [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secundary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • VAS for back pain and leg pain [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Health-related quality of life as measured by the SF-36 [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Healthy Questionnaire EQ-5D [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Neurological status [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Functional status [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Return to work (days) [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Analgesic Medication Use during the previous 14-day-time period [ Time Frame: Baseline assessment 1<45d pre-sequestrectomy, pre-transplantation (90 +/- 15d post-sequestrectomy) up to 60-months follow-up ]

      Secondary efficacy variable

      Early evaluation for efficacy will be performed at 12-months follow-up, primary evaluation for efficacy will be performed at 24-months follow-up, and final analysis will be performed at 60-months follow-up.

    • Physician assessments of ease of transplantation [ Time Frame: transplantation ]

      Outcome to quantify feasibility of procedure

      When all NDplus and NDbasic patients completed transplantation proced

      Information By: Tetec AG

      Dates:
      Date Received: May 16, 2012
      Date Started: August 2012
      Date Completion: August 2021
      Last Updated: April 12, 2016
      Last Verified: April 2016