Autologous Osteogenic Graft for Nonunion Fracture

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

4 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment NVD-003 for nonunion fractures?

Research shows that using autologous bone grafts (bone taken from the patient's own body) can effectively help heal nonunion fractures, as seen in studies where patients experienced pain relief and bone healing within a few months. This suggests that treatments like NVD-003, which involve using the patient's own cells, may also be effective in promoting bone healing. ^{1 2 3 4 5}

Is the autologous osteogenic graft safe for treating nonunion fractures?

The autologous osteogenic graft, derived from a patient's own stem cells, has been tested for safety in treating bone defects. In a study with six patients, the graft was stable, did not cause harm at the donor site, and was safely implanted without causing acute complications. ^{1 6 7 8 9}

How is the treatment NVD-003 for nonunion fractures different from other treatments?

NVD-003 is unique because it uses an autologous osteogenic graft, which means it uses the patient's own bone cells to promote healing, potentially reducing complications associated with donor sites compared to traditional methods like iliac crest bone grafting. ^{1 6 10 11 12}

Research Team

Philip McClure, MD

Principal Investigator

International Center for Limb Lengthening Baltimore

Pierre-Louis Docquier

Principal Investigator

UCL St.Luc Brussels

Eligibility Criteria

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

Bilateral CPT

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Fibula and tibia fusion with cancellous allograft vitalised with autologous bone marrow: first results for infected tibial non-union. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Autologous bone grafting versus bone morphogenetic protein treatment for nonunion of long bone fractures in adults：a Meta analysis]. [2020]

4. China pubmed.ncbi.nlm.nih.gov

[Surgical treatment for bone nonunion after massive allograft transplantation]. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The use of periosteally vascularized autografts to augment the fixation of large segmental allografts. [2005]

6. France pubmed.ncbi.nlm.nih.gov

Can the Reamer/Irrigator/Aspirator System replace anterior iliac crest grafting when treating long bone nonunion? [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of long bone non-unions with polytherapy: indications and clinical results. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept. [2022]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

The Reamer-Irrigator-Aspirator technique for manubriosternal non-union repair†. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Outcomes and complication rates of different bone grafting modalities in long bone fracture nonunions: a retrospective cohort study in 182 patients. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Nonunion treatment: iliac crest bone graft techniques. [2022]