A Prospective Multi-centre, Randomised, Controlled Study to Evaluate the Safety and Preliminary Effectiveness of NVD-001 for the Treatment of Low Grade Degenerative Lumbar Spondylolisthesis by Interbody Fusion (L1 - S1)

INTERVENTION: Experimental: NVD‐001 Autologous osteogenic cells in ECM with DBM At the Investigator's discretion, one or two interbody polyetheretherketone (PEEK) cage(s) filled and surrounded with NVD‐001. Active Comparator: Standard of Care Best standard of care in surgical practice At the Investigator's discretion, one or two interbody polyetheretherketone (PEEK) cage(s) filled and surrounded with autologous locally harvested cancellous bone (laminectomy) CONDITION: Spondylolisthesis PRIMARY OUTCOME: During the first year post surgery, safety will be assessed by:; ‐ Collecting all adverse events for incidence, severity, relatedness, required action and outcome.; ‐ Collecting all SAEs (also SAEs during second year follow‐up); ‐ Collecting Adverse Events of Special Interest (AESI) (also at 24 months post‐surgery) as part of local and systemic toxicity such as:; Signs of local toxicity of experimental product will be evaluated on CT and radiographic images by local and independent radiologist and include:; ‐‐ Trabecular bone resorption ; ‐‐ Intravertebral cystic changes; ‐‐ Soft tissue calcification/ossification; ‐‐ Peridiscal soft tissue swelling ; ‐‐ Hyperostosis; ‐‐ Tumour growth ; Signs of systemic toxicity will be evaluated on chest radiographs by local radiologist and include appearance of calcification/ ossification on serial X‐rays in comparison with preoperative X‐rays.; ‐‐ Ectopic bone formation ; ‐ Surgical intervention‐related safety parameters ; ‐ Safety laboratory parameters ; ‐ Safety evaluations including Electrocardiography, vital signs, physical and neurological examinations SECONDARY OUTCOME: ‐ Evaluation of fusion will be assessed on CT‐Scans(*) at 6, 9, 12 and 24 months post‐surgery by qualitative visual analysis called the "bridging trabecular bone scale" (Sys et al, 2011). ; (*) Coronal and sagittal computed tomography scan: spiral CT with thin acquisition of axial images, in Digital Imaging and Communications in Medicine (DICOM) format.; ‐ Evaluation of Non‐fusion will be assessed on Dynamic Radiographs at 6, 9, 12 and 24 months post‐surgery and considered as non‐fusion if at least one of the following signs occurs: translational motion more than 3 mm; angular motion more than 5deg; vacuum phenomenon in operated disc. ; ‐ Evaluation of bone production will be done on CT images and will be quantified by using specific software at 6, 9, 12 and 24 months post‐surgery. Two quantitative parameters will be addressed on serial CT with discharge CT data as baseline (of the patient's spine condition):; ‐‐ Surface of new bone production (Huang et al, 2014) ; ‐‐ Determination of Hounsfield Unit (HU) in selected areas (in the PEEK cage(s) and in the entire disc).; ‐ Functional assessment by means of Oswestry Disability Index (ODI) at screening, 1, 6, 9, 12 and 24 months post‐surgery.; ‐ Pain assessment by means of Brief Pain Inventory (BPI) at screening, pre‐operation, discharge, 1, 6, 9, 12 and 24 months post‐surgery.; ‐ Overall Treatment Effect scale (OTE) at 1, 6, 9, 12 and 24 months post‐surgery.; ‐ Quality of life assessment by means of questionnaire EuroQoL 5 Dimensions (EQ‐5D‐5L) at screening, 9, 12 and 24 months post‐surgery.; ‐ Surgical parameters such as duration of surgery, duration of postoperative hospital stay, subsequent surgical interventions (revision, removal, reoperation and supplemental fixation). INCLUSION CRITERIA: ‐Subject has understood and accepted to participate in the study according to all study procedures by signing the approved informed consent. ‐Male or female subjects aged >18 and is skeletally mature (epiphyses closed). ‐Subject has clinically important pain or neurological symptoms with or without claudication due to symptomatic degenerative spondylolisthesis grade I or II (Meyerding Classification). ‐Conservative treatment of disease has failed for at least 3 months since diagnosis. (ISASS 2011) ‐Subject has a preoperative ODI score > 30. ‐Subject has an indication for spinal fusion of one vertebral segment (L1‐S1) due to symptomatic degenerative spondylolisthesis grade I or II diagnosed by computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and/or dynamic radiography. ‐Subject is suitable for surgical operation and incorporation of the PEEK cage(s) by transforaminal lumbar interbody fusion (TLIF) or posterior lumbar inter