Safety and Preliminary Effectiveness of NVD-001 for the Treatment of Low Grade Degenerative Lumbar Spondylolisthesis

NCT03100032 | Completed Phase 1

• 2 other identifiers: NVD-CLN012016-002642-23
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 12

Brief Summary

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).

Conditions

Spondylolisthesis

Keywords

Spinal Fusion; Lumbar Interbody Fusion; Autologous Stem Cell Therapy; Bone Graft; Demineralized Bone Matrix; Polyetheretherketone (PEEK) cage

Outcome Measures

Primary Outcomes (8)

• NVD-001 (nocc AEs)

  Number of Adverse Events (AEs) severity, relatedness to the product or procedure, required action and outcome, up to 12 months post-surgery

  12 months

• NVD-001 (npat AEs)

  Number of participants presenting Adverse Events (AEs).

  12 months

• NVD-001 (nocc SAEs)

  Number of serious Adverse Events (SAEs), severity, relatedness to the product or procedure, required action and outcome.

  24 months

• NVD-001 (npatSAEs)

  Number of participants presenting Serious Adverse Events (AEs).

  24 months

• NVD-001 (nocc AESI)

  Number of Adverse Events of Special Interest (AESI) using lumbar spine CT and radiographic images.

  24 months

• NVD-001 (npat AESI)

  Number of participants with Adverse Events of Special Interest (AESI) using lumbar spine CT and radiographic images.

  24 months

• NVD-001 (npat Safety X-rays)

  Number of participants with appearance or absence of calcification/ ossification and ectopic bone formation in comparison with preoperative, as determined by chest X-rays.

  24 months

• NVD-001 (npat Safety Post-Op)

  Number of participants with occurrence or absence of surgical intervention-related safety parameters such as infection and peri- and post-operative blood loss volume

  1 month

Secondary Outcomes (8)

• NVD-001 (LSF)

  24 months

• NVD-001 (ODI)

  24 months

• NVD-001 (BPI)

  24 months

• NVD-001 (OTE)

  24 months

• NVD-001 (QoL)

  24 months

Study Arms (2)

NVD-001

EXPERIMENTAL

Autologous osteogenic cells in ECM with DBM

Biological: NVD-001

Standard of Care

ACTIVE COMPARATOR

Best standard of care in surgical practice

Procedure: Standard of Care

Interventions

NVD-001 BIOLOGICAL

At the Investigator's discretion, one or two interbody polyetheretherketone (PEEK) cage(s) filled and surrounded with NVD-001.

NVD-001

Standard of Care PROCEDURE

At the Investigator's discretion, one or two interbody polyetheretherketone (PEEK) cage(s) filled and surrounded with autologous locally cancellous bone (laminectomy)

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• At screening, local laboratory safety test results are clinically acceptable and serology results for HIV, HBV, HCV, HTLV I/II and syphilis are in accordance with country specific requirements for donation of Human Body Material. At time of adipose tissue collection, central laboratory serology and molecular test panel for HIV, HBV, HCV, HTLV I/II and syphilis must be in accordance with Belgian specific requirements for release of Human Body Material.
• 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 (defined as a method which results in a failure rate of less than 1% per year) such as:
• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)

You may not qualify if:

• 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 displays drug or alcohol dependence, serious current illness, mental illness or extenuating circumstance or any other factors which, in the opinion of the Investigator, will interfere with study conduct or interpretation of the results.
• 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 is on a transplant list or having received a solid organ transplant at any point in the past.
• Pregnant or breast-feeding woman.
• Involved in or planning to engage in litigation related health problems.
• Subject is a prisoner.
• Subject had an acute fracture of the spine within 6 months prior V0a in the study.
• Subject is known to require additional surgery to the lumbar spinal region within the next 2 years after 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.

Sponsors & Collaborators

• Novadip Biosciences: lead

Study Sites (12)

Hôpital Erasme - Neurosurgery Department

Brussels, 1070, Belgium

Location

Universitair ziekenhuis Brussel - Brussels Health Campus - Department of Orthopaedics and Traumatology

Brussels, 1090, Belgium

Location

Saint-Luc University Hospital

Brussels, 1200, Belgium

Location

Algemeen Ziekenhuis Monica O.L.V. - Campus Deurne

Deurne, 2100, Belgium

Location

Ziekenhuis Oost-Limburg, Campus Sint-Jan

Genk, 3600, Belgium

Location

Centre Hosp. Univ. UCL - Namur site Godinne - Service de neurochirurgie

Yvoir, 5530, Belgium

Location

Fakultní nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultní nemocnice v Motole

Prague, 150 06, Czechia

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Centrum Medyczne Angelius Provita

Katowice, 40-611, Poland

Location

Szpital Św. Rafała

Krakow, 30-693, Poland

Location

Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im. W. Degi Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, 61-545, Poland

Location

MeSH Terms

Conditions

Spondylolisthesis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Spondylolysis; Spondylosis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Denis Dufrane, MD, PhD

  Novadip Biosciences

  STUDY DIRECTOR

• Christian Raftopoulos, MD, PhD

  Saint-Luc University Hospital, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: April 4, 2017
• Study Start: January 1, 2017
• Primary Completion: January 1, 2021
• Study Completion: June 1, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (6); CZ (2); PL (4)