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

Phase 1

Active, not recruiting

Interventions: Biological: NVD-003, an autologous 3D scaffold free osteogenic graft

Brief 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.

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.

Recruitment & 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.

Arm && Interventions

Group	Intervention	Description
NVD-003 bone graft implant	NVD-003, an autologous 3D scaffold free osteogenic graft	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Bone union	3-, 6-, 12- and 24-months post-GS	Assess changes in bone union (using Lane and Sandhu Scoring on CT-scan)
Long term Safety long-term (>12-24 months): Descriptive analysis	12-24 months post grafting surgery	Assess number of patients with NVD-003 related SAEs
Tibial length evaluation	3-, 6-, 12- and 24-months post-GS	Assess evolution tibial length (using CT-Scan)
Bone formation	3-, 6-, 12- and 24-months post-GS	Assess changes in bone formation (Using Lane and Sandhu Scoring on CT-Scan)
Bone remodeling	3-, 6-, 12- and 24-months post-GS	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

Locations (2): Cliniques Universitaires Saint-Luc
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Brussels, Belgium
Adult/Pediatric Limb Lengthening and Reconstruction - International Center for Limb Lengthening - Rubin Institute for Advanced Orthopedics Baltimore
🇺🇸
Baltimore, Maryland, United States