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

NCT ID: NCT05693558

Last Updated: 2024-01-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-24
• Study Completion Date: 2026-01-31

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.

Conditions

Congenital Pseudarthrosis of Tibia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

Bone correction and grafting surgery

Interventions

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

Bone correction and grafting surgery

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novadip Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip McClure, MD

Role: PRINCIPAL_INVESTIGATOR

International Center for Limb Lengthening Baltimore

Pierre-Louis Docquier

Role: PRINCIPAL_INVESTIGATOR

UCL St.Luc Brussels

Locations

Adult/Pediatric Limb Lengthening and Reconstruction - International Center for Limb Lengthening - Rubin Institute for Advanced Orthopedics Baltimore

Baltimore, Maryland, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Countries

United States; Belgium

References

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.

Reference Type: BACKGROUND

PMID: 30996736 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29113460 (View on PubMed)

Other Identifiers

2022-001282-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NVD003-CLN02 CPT

Identifier Type: -

Identifier Source: org_study_id