UMIN-CTR Clinical Trial

Basic information
Public title	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).
Acronym	Safety and Preliminary Effectiveness of NVD-001 for the Treatment of Low Grade Degenerative Lumbar Spondylolisthesis. ( Spine1 )
Scientific Title	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).
Scientific Title:Acronym	Safety and Preliminary Effectiveness of NVD-001 for the Treatment of Low Grade Degenerative Lumbar Spondylolisthesis. ( Spine1 )
Region	Europe

Condition
Condition	Spondylolisthesis
Classification by specialty	Orthopedics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	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).
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I,II

Assessment
Primary outcomes	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
Key secondary outcomes	- 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).

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	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.
Interventions/Control_2	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)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <
Age-upper limit	Not applicable
Gender	Male and Female
Key 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 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. -Subject is, in the Investigator?s opinion, psychosocially, mentally and physically able to fully comply with this protocol, including the postoperative regimen and follow-up visits. -Safety laboratory test results and pre-surgery serology are clinically acceptable to undergo surgery as applicable Serology panel for HIV, HBV, HCV, HTLV I/II and syphilis must be negative. -Women of childbearing potential (WOCBP) including peri-menopausal women who have had a menstrual period within 1 year prior to surgery have to have a negative pregnancy test. Results have to be available and negative for the patient to be entered in the study. -WOCBP have to use an effective method of birth control 2 months prior to study entry or to surgical intervention date and throughout the study duration.
Key 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) <= to 18.5 or has a BMI of >= to 40, or >= to 35 and experiencing obesity-related health conditions, such as high blood pressure or diabetes. -Overt or active local or systemic infection. -Subject has a history of previously attempted spinal fusion at the same level, or spine level immediately adjacent to the level to be operated. Decompressive surgery alone (laminectomy) is not an exclusion criterion. -Pregnant or breast-feeding woman. -Subject had an acute fracture of the spine within 6 months prior enrolment in the study. -Subject is currently taking chronically any medications that might affect bone metabolism or the quality of bone formation such as but not limited to bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressants or immunotherapy. -Subject is positive for human immunodeficiency virus (HIV) 1 or 2, hepatitis B or C, human T-cell lymphotropic virus (HTLV) 1 or 2, or syphilis at screening. -Any clinically relevant chronic disease associated with renal or hepatic insufficiency or any chronic disease of such severity that surgery could be detrimental to the survival of the patient. -Subject is on chronic immunosuppressive therapy due to inflammatory or systemic disease. -Subject has a history of any autoimmune disease. -(other crietria apply)
Target sample size	36

Research contact person
Name of lead principal investigator	1st name Christian Middle name Last name Raftopoulos, MD, PhD
Organization	Saint-Luc University Hospital
Division name	Department of Neurosurgery
Zip code	1200
Address	Hippocrate Avenue 10 - 1200 Brussels - Belgium
TEL	3227641088
Email	christian.raftopoulos@uclouvain.be

Public contact
Name of contact person	1st name Patricia Middle name Last name De Cock, MD, PhD
Organization	Novadip Biosciences
Division name	Medical Officer
Zip code	1435
Address	Watson and Crick Hill, Rue Granbonpre 11 Bldg, B-1435 Mont-Saint-Guibert - Belgium
TEL	3210779220
Homepage URL	https://www.novadip.com/
Email	clinical@novadip.com

Sponsor
Institute	Novadip Biosciences Watson and Crick Hill Rue Granbonpre 11 B-1435 Mont-Saint-Guibert - Belgium
Institute
Department

Funding Source
Organization	Novadip Biosciences Watson and Crick Hill Rue Granbonpre 11 B-1435 Mont-Saint-Guibert - Belgium
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization	Belgium

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Comite d Ethique Hospitalo-Facultaire Universite Catholique de Louvain Faculte de medecine
Address	Avenue Hippocrate 55-14, Tour Harvey niv 0, 1200 Brussel- Belgium
Tel	3227645514
Email	commission.ethique-saint-luc@uclouvain.be

Secondary IDs
Secondary IDs	YES
Study ID_1	EudraCT 2016-002642-23
Org. issuing International ID_1	EMA
Study ID_2	NCT03100032
Org. issuing International ID_2	U.S. National Institutes of Health
IND to MHLW

Institutions
Institutions	(none in Japan)

Other administrative information
Date of disclosure of the study information	2017 Year 02 Month 08 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2016 Year 08 Month 08 Day
Date of IRB	2016 Year 11 Month 28 Day
Anticipated trial start date	2017 Year 01 Month 01 Day
Last follow-up date	2020 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 02 Month 08 Day
Last modified on	2019 Year 08 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029156

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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