E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients diagnosed with symptomatic degenerative spondylolisthesis grade I or II with an indication for spinal fusion of one vertebral segment (L1-S1). |
Pacjenci z objawowym kręgozmykiem zwyrodnieniowym niskiego stopnia - I lub II stopień, poddawanych operacji fuzji międzytrzonowej jednego segmentu kręgowego (L1 - S1). |
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E.1.1.1 | Medical condition in easily understood language |
Patients diagnosed with symptomatic degenerative spondylolisthesis grade I or II with an indication for spinal fusion of one vertebral segment (L1-S1). |
Pacjenci z objawowym kręgozmykiem zwyrodnieniowym niskiego stopnia - I lub II stopień, poddawanych operacji fuzji międzytrzonowej jednego segmentu kręgowego (L1 - S1). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077991 |
E.1.2 | Term | Lumbar spondylolisthesis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety (local and systemic) of a specific surgical intervention with the use of NVD-001 (AEs, AESI, SAEs) in patients with symptomatic low-grade degenerative spondylolisthesis grade I or II undergoing surgery for spinal fusion of one vertebral segment (L1-S1). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety (local and systemic) of a commonly used surgical intervention with the use of locally harvested cancellous bone (laminectomy).
• To determine the clinical efficacy of one level spinal lumbar interbody fusion with NVD 001 by imaging assessments.
• To determine the clinical efficacy of one level spinal lumbar interbody fusion with locally harvested cancellous bone by imaging assessments.
• For both groups:
- Functional assessment
- Pain assessment
- Subsequent surgical interventions (revision, removal, reoperation and supplemental fixation)
• For both groups:
- To record peri- and postoperative blood loss
- To record duration of surgery
- To record the number of postoperative hospital days stays
- To assess Overall Treatment effect evaluation
- QoL assessment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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) at Visit V0a.
• Subject has clinically important pain or neurological symptoms at V0a 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 intervertebral fusion (PLIF) by minimally invasive or open approach in one mobile segment (L1- S1) with bilateral rigid fixation. No posterolateral lumbar fusion (PLF) technique is allowed.
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E.4 | Principal exclusion criteria |
• Subject has known history of hypersensitivity or anaphylactic reaction to PEEK.
• Due to medical or other reasons spine fusion cannot be delayed for up to 6 months.
• Indications for spinal fusion other than symptomatic degenerative spondylolisthesis grade I and II (Meyerding Classification).
• Subject has documented metabolic disease such as but not limited to severe osteoporosis, osteogenesis imperfect, or osteomalacia.
• Subject with poorly controlled diabetes mellitus as assessed by glycohaemoglobin (HbA1c) > 8% (at least 2 values per year for last 2 years)
• Subject is underweight, i.e. body mass index (BMI) ≤18.5 or has a BMI of ≥40, or ≥35 and experiencing obesity-related health conditions, such as high blood pressure or diabetes at V0a.
• Overt or active local or systemic infection, including latent infection around (area of) the future surgical implant site.
• Subject has a history of previously attempted spinal fusion at the same level, or spine level immediately adjacent to the level to be operated on in this study. Decompressive surgery alone (laminectomy) is not an exclusion criterion.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Collecting all adverse events for incidence, severity, relatedness, required action and outcome, up to 12 months post-surgery.
• Collecting all SAEs, up to 24 months post-surgery.
• Collecting Adverse Events of Special Interest (AESI), up to 24 months post-surgery as part of local and systemic toxicity such as
o Signs of local toxicity of experimental product will be evaluated on CT and radiographic images by the local radiologist and include:
• Trabecular bone resorption
• Intravertebral cystic changes
• Soft tissue calcification/ossification
• Peridiscal soft tissue swelling
• Hyperostosis
• Tumour growth
o Signs of systemic toxicity will be evaluated on chest radiographs and include appearance of calcification/ ossification on serial X-rays in comparison with preoperative X-rays.
• Ectopic bone formation
• Surgical intervention related safety parameters such as but not limited to:
o Infection
o Peri- and postoperative blood loss
o Safety laboratory parameters
o Safety evaluations including electrocardiography, vital signs, physical and neurological examinations |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months post-surgery and follow-up at 24 months. |
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E.5.2 | Secondary end point(s) |
• 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”.
• Evaluation of Non-fusion will be assessed on Dynamic Radiographs at 6, 9, 12 and 18 months post-surgery and considered as non-fusion if at least one of the following signs occurs: translational motion > 3 mm; angular motion > 5°; 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.
• Functional assessment by means of Oswestry Disability Index (ODI) at screening, 1, 6, 9, 12, 18 and 24 months post-surgery
• Pain assessment by means of Brief Pain Inventory (BPI) at screening, pre-operation, discharge, 1, 6, 9, 12, 18 and 24 months post-surgery
• Overall Treatment Effect scale (OTE) at 1, 6, 9, 12, 18 and 24 months post-implant procedure.
• Quality of life assessment by means of questionnaire EuroQoL 5 Dimensions (EQ-5D-5L) at screening, 9, 12, 18 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). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 9, 12, 18 and 24 months post-surgery. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Best standard of care in surgical practice |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
ostatnia wizyta ostatniego pacjenta |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |