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

Congenital Pseudarthrosis of Tibia Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05693558
• Other study ID #: NVD003-CLN02 CPT
• Secondary ID: 2022-001282-12
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 24, 2022
• Est. completion date: January 2026

Study information

• Verified date: January 2024
• Source: Novadip Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 8 Years

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Pseudarthrosis of Tibia
• Pseudarthrosis

Intervention

Biological:
• NVD-003, an autologous 3D scaffold free osteogenic graft
Bone correction and grafting surgery

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
United States	Adult/Pediatric Limb Lengthening and Reconstruction - International Center for Limb Lengthening - Rubin Institute for Advanced Orthopedics Baltimore	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novadip Biosciences

Countries where clinical trial is conducted

United States,  Belgium, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Tibial length evaluation	Assess evolution tibial length (using CT-Scan)	3-, 6-, 12- and 24-months post-GS
Secondary	Bone formation	Assess changes in bone formation (Using Lane and Sandhu Scoring on CT-Scan)	3-, 6-, 12- and 24-months post-GS
Secondary	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
Secondary	Bone union	Assess changes in bone union (using Lane and Sandhu Scoring on CT-scan)	3-, 6-, 12- and 24-months post-GS