NVD-003 in the Treatment of Congenital Pseudarthrosis of the Tibia

A Proof-of-concept Study With NVD-003, an Autologous Osteogenic Bone Graft, in the Treatment of Congenital Pseudarthrosis of the Tibia in Pediatric Patients.

A single arm, multi-country, multi-center study in pediatric patients, suffering from congenital pseudarthrosis of the tibia (CPT), treated during the primary surgical intervention with NVD-003, an autologous 3D scaffold free osteogenic graft.

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Pseudarthrosis of Tibia
• Intervention / Treatment: Biological: NVD-003, an autologous 3D scaffold free osteogenic graft

Detailed Description

Congenital pseudarthrosis is a rare disorder of unknown aetiology and variable history that manifests itself as a non-union or pseudarthrosis of fractures that develop spontaneously or following minor trauma. It can be defined as a disorder of the diaphysis which is revealed by either pseudarthrosis at birth or by a pathological fracture presenting in bone with modifications such as bowing, narrowing of the medullary canal or a cyst. Although uncommon, CPT is the most frequently observed type of congenital pseudarthrosis. Its incidence is reported to be between 1:140,000 to 1:250,000 live births.

Autologous bone grafting is considered the gold standard approach as this material vascularizes and integrates with surrounding bone, minimizing the risk of infection, dislodgement, or break-down.

NVD-003 is a scaffold free 3D osteogenic graft derived from autologous adipose stem cells which become embedded in their extracellular matrix and combined with hydroxyapatite/beta-tricalcium phosphate (HA/βTCP) particles.

NVD-003 is intended to promote bone formation, supporting the physiological bone healing process in severe pathophysiological conditions such as hypoxia, lack of mineralized callus formation, bone resorption and low osteogenicity.

• Study Type: Interventional
• Enrollment (Estimated): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Adult/Pediatric Limb Lengthening and Reconstruction - International Center for Limb Lengthening - Rubin Institute for Advanced Orthopedics Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with congenital pseudarthrosis of the tibia (with or without NF1) and presenting with a non-healing Paley type 3 or 4 fracture.
• Minimum weight of 5kg/11lbs.
• Maximum 2 previous failed surgical orthopaedic interventions to treat the primary CPT fracture.
• Acceptable serology and molecular test results excluding the presence of viruses
• Satisfactory general health condition to undergo surgeries (ATC and GS) with anaesthesia as per local standards.
• The patient's parent(s) and/or legal guardian(s) provided written informed consent and accepted the participation of the patient in the trial.

Exclusion Criteria:

• Bilateral CPT.
• Presence of CPT without a fracture of the tibia (Paley type 1 and 2).
• More than 2 failed surgical attempt(s) to treat the primary tibial fracture.
• Evidence of plexiform neurofibroma of any size or nodular fibroma ≥ 1.2in/3cm on the ipsilateral leg.
• Clinically significant infection at the target grafting site or systemic infection.
• Presence of clinically significant hematologic, renal, hepatic, and coagulation laboratory abnormalities (i.e., CBC, PT/INR, Chem-7, and LFTs, etc.).
• Presence of any auto-immune disease, with exception of well controlled diabetes type 1 or auto-immune thyroid disorders.
• Any history of experimental therapy with another investigational drug within 60 days prior to screening.
• Presence of active tumour.
• Documented metabolic bone disease or any disorder, such as but not limited to osteogenesis imperfecta and osteomalacia, that could interfere with the bone healing and bone metabolism.
• Chronic, ongoing, or planned use of medications that might affect bone metabolism or bone quality such as bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressant therapy or immunotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVD-003 bone graft implant; The study includes 2 important surgical procedures, the Adipose Tissue Collection (ATC) and the Grafting Surgery (GS) and 3 stages; Stage 1: A screening, adipose tissue collection & NVD 003 manufacturing period.; Stage 2: Grafting surgery and 12-month post-GS follow-up period.; Stage 3: long-term safety follow-up period (from post-month 12 to month 24).	Biological: NVD-003, an autologous 3D scaffold free osteogenic graft; Bone correction and grafting surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary objective: safety short (≤3 months) and mid long-term (>3-12 months): : Descriptive analysis	Assess number of patients with NVD-003 related (S)AEs	Up to 12 months post-grafting surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term Safety long-term (>12-24 months): Descriptive analysis	Assess number of patients with NVD-003 related SAEs	12-24 months post grafting surgery
Tibial length evaluation	Assess evolution tibial length (using CT-Scan)	3-, 6-, 12- and 24-months post-GS
Bone formation	Assess changes in bone formation (Using Lane and Sandhu Scoring on CT-Scan)	3-, 6-, 12- and 24-months post-GS
Bone remodeling	Assess changes in bone remodeling (using Lane and Sandhu Scoring on CT-scan) Based on Dual Energy CT-scan (DECT or Spectral CT), information of low- and high-energy photons is collected, allowing to uncover differences in energy-dependent attenuation, facilitating composition of NVD 003 and surrounding tissue and define bone mineral density) at 3-, 6-, and 12-months post-GS	3-, 6-, 12- and 24-months post-GS
Bone union	Assess changes in bone union (using Lane and Sandhu Scoring on CT-scan)	3-, 6-, 12- and 24-months post-GS

Collaborators and Investigators

• Sponsor: Novadip Biosciences
• Investigators: Principal Investigator: Philip McClure, MD, International Center for Limb Lengthening Baltimore; Principal Investigator: Pierre-Louis Docquier, UCL St.Luc Brussels

Publications and helpful links

General Publications

• Paley D. Congenital pseudarthrosis of the tibia: biological and biomechanical considerations to achieve union and prevent refracture. J Child Orthop. 2019 Apr 1;13(2):120-133. doi: 10.1302/1863-2548.13.180147.
• Dufrane D. Impact of Age on Human Adipose Stem Cells for Bone Tissue Engineering. Cell Transplant. 2017 Sep;26(9):1496-1504. doi: 10.1177/0963689717721203.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: pediatric; bone graft; autologous; Cellular therapy; congenital; Tissue Engineered Therapy; non-union; pseudarthrosis
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Fractures, Ununited; Pseudarthrosis
• Other Study ID Numbers: NVD003-CLN02 CPT; 2022-001282-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No