UMIN-CTR Clinical Trial

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

Spondylolisthesis

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

NO

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

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).

Study type

Interventional

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

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

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

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

Name of contact person

1st name	Denis
Middle name
Last name	Dufrane, MD, PhD

Organization

Novadip Biosciences

Division name

Medical Officer

Zip code

1435

Address

Watson and Crick Hill, Rue Granbonpre 11, B-1435 Mont-Saint-Guibert - Belgium

TEL

3210779220

Homepage URL

https://www.novadip.com/

Email

clinical@novadip.com

Institute

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

Institute

Department

Personal name

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

Co-sponsor

Name of secondary funder(s)

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

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

(none in Japan)

Date of disclosure of the study information

2017

Year

02

Month

08

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

36

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

Recruitment status

Completed

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 related information

Registered date

2017

Year

02

Month

08

Day

Last modified on

2021

Year

05

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029156