A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of Phase I—a short report

Abstract

NOVOCART® Disk plus, an autologous cell compound for autologous disk chondrocyte transplantation, was developed to reduce the degenerative sequel after lumbar disk surgery or to prophylactically avoid degeneration in adjacent disks, if present. The NDisc trial is an ongoing multi-center, randomized study with a sequential phase I study within the combined phase I/II trial with close monitoring of tolerability and safety. Twenty-four adult patients were randomized and treated with the investigational medicinal product NDisc plus or the carrier material only. Rates of adverse events in Phase I of this trial were comparable with those expected in the early time course after elective disk surgery. There was one reherniation 7 months after transplantation, which corresponds to an expected reherniation rate. Immunological markers like CRP and IL-6 were not significantly elevated and there were no imaging abnormalities. No indications of harmful material extrusion or immunological consequences due to the investigational medicinal product NDplus were observed. Therefore, the study appears to be safe and feasible. Safety analyses of Phase I of this trial indicate a relatively low risk considering the benefits that patients with debilitating degenerative disk disease may gain.

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

“…This treatment is a combination of autologous disc chondrocytes and a self‐polymerizing hydrogel (http://clinicaltrials.gov study identifier NCT01640457) that is already being used clinically for articular cartilage repair in the knee. Preliminary results from the Phase I trial of this therapy indicate the risks of adverse events occurring are comparable to elective disc surgery …”

Long‐Term Pathology of Ovine Lumbar Spine Degeneration Following Injury Via Percutaneous Minimally Invasive Partial Nucleotomy

“…However, in most cases, these therapeutic approaches remain in basic science or preclinical studies . Further development is also necessary within the context of a previously tested clinical approach …”

“…7 Further development is also necessary within the context of a previously tested clinical approach. [8][9][10] The basis of successful preclinical development is establishing a representative animal model to serve as an analog for human spine pathology, for example, in the case of lumbar disc herniation. To date, several small animal preclinical studies have used mouse, rabbit, rat, and canine models to study IDD.…”

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

“…Intradiscal PRP injection seems safe; however, its efficacy remains unclear . Chondrocyte transplantation studies showed some positive results in a small number of participants; further studies are needed to show efficacy . Experimental studies demonstrated cell leakage following injection with ectopic calcifications as a potential complication, thus motivating the need for a cell carrier to help enhance cell injections …”

“…(126)(127)(128)(129) Chondrocyte transplantation studies showed some positive results in a small number of participants; further studies are needed to show efficacy. (130)(131)(132) Experimental studies demonstrated cell leakage following injection with ectopic calcifications as a potential complication, thus motivating the need for a cell carrier to help enhance cell injections. (133,134) IVD repair techniques or implant biomaterials for annulus closures and NP replacement have the potential to repair the IVD, yet also create a risk for reherniation, which can cause nerve compression and the possibility of a recurrent painful condition or worsening of a condition.…”