Clinical trial NCT05693558: NVD-003 in the Treatment of Congenital Pseudarthrosis of the Tibia
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Congenital Pseudarthrosis of Tibia
Keywords: Tissue Engineered Therapy
bone graft
autologous
pediatric
congenital
non-union
pseudarthrosis
Cellular therapy
Lead sponsor: Novadip Biosciences
Sponsor class: INDUSTRY
First posted: 2023-01-23
Enrollment: 4
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary objective: safety short (≤3 months) and mid long-term (>3-12 months): : Descriptive analysis
timeFrame: Up to 12 months post-grafting surgery
Secondary outcomes:
measure: Long term Safety long-term (>12-24 months): Descriptive analysis
timeFrame: 12-24 months post grafting surgery
measure: Tibial length evaluation
timeFrame: 3-, 6-, 12- and 24-months post-GS
measure: Bone formation
timeFrame: 3-, 6-, 12- and 24-months post-GS
measure: Bone remodeling
timeFrame: 3-, 6-, 12- and 24-months post-GS
measure: Bone union
timeFrame: 3-, 6-, 12- and 24-months post-GS
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Adult/Pediatric Limb Lengthening and Reconstruction - International Center for Limb Lengthening - Rubin Institute for Advanced Orthopedics Baltimore
state: Maryland
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
Study officials:
affiliation: International Center for Limb Lengthening Baltimore
name: Philip McClure, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCL St.Luc Brussels
name: Pierre-Louis Docquier
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.