Autologous Osteogenic Graft for Nonunion Fracture

Not currently recruiting at 1 trial location

Overseen By Houda Khamis, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Novadip Biosciences

Must not be taking: Bisphosphonates, Steroids, Methotrexate, others

Disqualifiers: Bilateral CPT, Active tumour, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NVD-003, a special type of bone graft, for children with congenital pseudarthrosis of the tibia (CPT). CPT is a rare bone disorder where the shinbone doesn't heal properly, causing fractures that don't mend. The trial involves surgeries to collect and implant the graft to determine if it helps heal these stubborn fractures. Children with a chronic non-healing fracture in their shinbone who have undergone no more than two surgeries might be suitable for this study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using medications that might affect bone metabolism or bone quality, such as bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressant therapy, or immunotherapy.

What prior data suggests that this osteogenic graft is safe for pediatric patients?

Research has shown that NVD-003 is safe to use. In one study involving four children with congenital pseudarthrosis of the tibia (CPT), all experienced stable bone healing after receiving the graft. Importantly, these cases reported no safety issues.

Additionally, data from a five-year follow-up suggests that NVD-003 integrates well with bone and remains stable over time, helping to create a strong and lasting bone connection. These findings indicate that NVD-003 is well-tolerated, with no significant side effects observed so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for nonunion fractures, which often involve bone grafts from donors or synthetic materials, NVD-003 is unique because it uses the patient's own cells to promote healing. This autologous approach involves collecting adipose tissue (fat) from the patient to create a personalized bone graft. Researchers are excited about NVD-003 because it could potentially reduce the risk of rejection and complications, leading to a more natural and effective healing process. Additionally, the use of the patient's own cells might enhance integration and regeneration at the fracture site, offering hope for faster and more reliable recovery.

What evidence suggests that NVD-003 might be an effective treatment for congenital pseudarthrosis of the tibia?

Research has shown that NVD-003, the treatment under study in this trial, holds promise for treating bone issues such as congenital pseudarthrosis of the tibia (CPT). In one study, 89% of patients experienced successful bone healing 24 months after receiving the treatment. Another study found it to be 88% effective in patients with severe bone healing issues, including both children and adults. NVD-003 uses a patient's own cells to help grow new bone tissue. This method has demonstrated positive results even in challenging medical cases, offering hope for those with CPT. ^{1 2 3 4 5}

Who Is on the Research Team?

Philip McClure, MD

Principal Investigator

International Center for Limb Lengthening Baltimore

Pierre-Louis Docquier

Principal Investigator

UCL St.Luc Brussels

Are You a Good Fit for This Trial?

This trial is for children with a rare bone condition called congenital pseudarthrosis of the tibia, who have had no more than two unsuccessful surgeries to fix it. They must be in good health overall, weigh at least 11 pounds, and not have certain other medical conditions or infections that could affect bone healing.

Inclusion Criteria

The patient's parent(s) and/or legal guardian(s) provided written informed consent and accepted the participation of the patient in the trial

My blood tests for viruses are negative.

I am healthy enough to have surgery with anesthesia.

Exclusion Criteria

Presence of clinically significant hematologic, renal, hepatic, and coagulation laboratory abnormalities (i.e., CBC, PT/INR, Chem-7, and LFTs, etc.)

Any history of experimental therapy with another investigational drug within 60 days prior to screening

Bilateral CPT

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Adipose Tissue Collection & NVD-003 Manufacturing

Collection of adipose tissue and manufacturing of the NVD-003 graft

4-6 weeks

1 visit (in-person)

Grafting Surgery and Initial Follow-up

Grafting surgery followed by a 12-month post-surgery follow-up period

12 months

Regular visits for monitoring (in-person)

Long-term Safety Follow-up

Monitoring of long-term safety from month 12 to month 24 post-surgery

12 months

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• NVD-003

Trial Overview The study is testing NVD-003, an innovative graft made from the patient's own cells designed to heal bones without needing a scaffold. It's given during surgery as part of this single-group study involving multiple countries and centers.

How Is the Trial Designed?

Group I: NVD-003 bone graft implant Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Novadip Biosciences

Lead Sponsor

Trials

6

Recruited

90+

Published Research Related to This Trial

A systematic review of 24 studies on spinal fusion procedures found that a composite bone substitute demonstrated safety and efficacy comparable to autologous bone grafts, with some superior outcomes, based on a high-quality RCT.

Most studies included in the review had a high incidence of bias, indicating that while allografts and synthetic grafts are used, their efficacy and safety need to be carefully evaluated before use in spinal fusion procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal fusion procedures in the adult and young population: a systematic review on allogenic bone and synthetic grafts when compared to autologous bone. Salamanna, F., Tschon, M., Borsari, V., et al.[2021]

Citations

1. novadip.com novadip.com/press-releases/novadip-releases-five-year-follow-up-results-for-nvd003-regenerative-treatment-for-severe-bone-non-union-of-lower-limb/

Novadip releases five-year follow-up results for NVD003, ... No refractures were reported during long-term follow-up at five years. At 24-months post-implantation, 89% of patients achieved bone union.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12470636/

An Autologous Human Adipose Stem Cell-Derived 3D ... NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions. Keywords: autograft, bone ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07112443

NCT07112443 | A Study to Assess How Effective and Safe ... The purpose of this study is to assess the efficacy and safety of NVD003 in pediatric participants with unilateral Congenital Pseudarthrosis of the Tibia (CPT) ...

4. firstwordpharma.com firstwordpharma.com/story/5930864

Novadip reports 12-month results from phase 1b/2a trial of ... 88% efficacy demonstrated across all patients (n=17) treated with NVD003 to date (nine adults with bone non-union and eight children with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06335394

NCT06335394 | Prospective Study in Adults Evaluating ... The goal of this clinical trial is to evaluate the safety and preliminary efficacy of the autologous 3D osteogenic implant NVD-003 for bone reconstruction for ...